Automated and precise device for plaque detection, monitoring and removal

Abstract

Described herein are automated devices for detecting and removing dental biofilm. In some embodiments, the disclosed subject matter includes devices for applying a suspension comprising iron oxide nanoparticles to teeth to chemically treat and mechanically remove dental biofilm. In some embodiments, the disclosed subject matter includes devices for applying a suspension comprising iron oxide nanoparticles and hydrogen peroxide to teeth to kill bacteria within the biofilm matrix and degrade the biofilm matrix and assemble the iron oxide nanoparticles into autonomous magnetic bristles or antibacterial robots to mechanically remove the biofilm. Also disclosed herein are devices and methods for real-time detection of dental plaque and monitoring of dental plaque removal.

Description

[0001] Cross-references to related applications

[0002] 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

[0003] Maintaining healthy teeth and gums requires regular self-oral care, such as brushing, flossing, and using antibacterial mouthwash. The American Dental Association recommends that adults and children brush their teeth twice a day. However, brushing is often done less than recommended, such as fewer times a day or less at recommended intervals. Reasons for not brushing according to recommendations may include, for example, the time and effort required to satisfactorily clean all teeth in the upper and lower jaws, user boredom during the activity, hand dexterity, and lack of interest in performing similar daily tasks. Furthermore, ideal plaque removal requires multiple steps, such as flossing (between teeth) and opening the mouth to chemically kill bacteria.

[0004] Inadequate oral hygiene can lead to biofilm formation. A biofilm is a structured community of bacterial cells surrounded by an extracellular polymeric matrix (e.g., exopolysaccharide (EPS)). It acts as a barrier, providing resistance to antimicrobial agents, cohesive forces within the biofilm structure, and mechanical stability for strong adhesion to surfaces. Biofilms forming on teeth are associated with dental caries (cavities), gingivitis, and periodontal disease.

[0005] Some techniques for combating dental biofilms are largely inadequate and cumbersome because they cannot simultaneously kill and physically remove bacteria, requiring dexterous manual removal of the biofilm, such as brushing and flossing. Certain antibacterial agents, such as antiseptics and mouthwashes, cannot break down the biofilm matrix, have limited effectiveness against bacteria embedded within the protected biofilm structure, and the biofilm retains the ability to rapidly rebuild itself if biofilm fragments and bacteria are not removed. While some devices and methods are available for mechanical plaque removal in dental clinics (scaling) and at home (toothbrush, floss, and electric toothbrushes), they require dexterity.

[0006] The technologies discussed above pose challenges to consumers who face the risk of plaque buildup and oral diseases due to lack of adherence, as well as to older adults with poor hand dexterity and patients with physical and cognitive impairments.

[0007] These challenges are exacerbated by the lack of available technologies for real-time detection and monitoring of plaque accumulation or oral health conditions associated with plaque biofilm.

[0008] Accordingly, there is a need for a device that can simultaneously achieve plaque detection, monitoring, and removal in an automated manner with high precision. SUMMARY

[0009] Devices and methods for removing dental biofilm from teeth and eradicating bacteria within such dental biofilm are described herein.

[0010] In certain embodiments, the present disclosure provides an oral care device. An example device includes a flexible mouthpiece having an upper channel to fit over the upper teeth and a lower channel to fit over the lower teeth of a user. In certain embodiments, the mouthpiece includes one or more magnetic elements and a vibrating motor. In certain embodiments, the one or more magnetic elements include a permanent magnet and / or an electromagnet adapted to apply a magnetic field to a biofilm to drive iron oxide nanoparticles to assemble into an antibacterial robot or autonomous magnetic bristle or robot.

[0011] In certain embodiments, the oral care device of the present disclosure further includes a photodetector or an RGB sensor. In certain embodiments, the photodetector is coupled to a light emitting diode.

[0012] In certain embodiments, the upper channel and the lower channel of the mouthpiece of the present disclosure house a suspension including iron oxide nanoparticles, wherein the upper channel and the lower channel of the mouthpiece are to provide contact between the suspension and the surfaces of the upper teeth, lower teeth, interdental, and gingival of the user.

[0013] In certain embodiments, the upper channel and the lower channel of the mouthpiece house a suspension including iron oxide nanoparticles and a component selected from the group consisting of: hydrogen peroxide, urea peroxide, an enzyme, an antibacterial compound, a fluoride ion source, an abrasive compound, a flavonoid, a terpenoid, a polyphenol, a proanthocyanidin, a tannin, a coumarin, a surfactant, a detergent, glycerol, rose bengal, a perborate, a meta-periodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof. In certain embodiments, the suspension includes hydrogen peroxide. In certain embodiments, the suspension includes one or more enzymes. In certain embodiments, the one or more enzymes is a mutanase, a dextranase, or a combination thereof.

[0014] In certain embodiments, the suspension includes 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-sulphonic 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, and fluorescent dyes including 10-Acetyl-3,7-dihydroxyphenoxazine, Terephthalic acid, Homovanillic acid, 2-[6-(4-aminophenoxy)-3-oxo-3H-xanthen-9-yl]-benzoic acid, (2-[6-(4'-hydroxy)phenoxy-3H-xanthene-3-on-9-yl]benzoic acid, 2',7'-Dichlorofluorescein diacetate, 2,7-Dichlorodihydrofluorescein diacetate, Coumarin Boronic Acid, Coumarin Boronic Acid pinacolate ester, Dihydrorhodamine 123, Lucigenin, Dihydroethidium.

[0015] In certain embodiments, the present disclosure provides methods for removing dental biofilm. An example method includes inserting an oral care device of the present disclosure into a user's mouth, applying a suspension including iron oxide nanoparticles to the upper and lower channels of the mouthpiece, driving the iron oxide nanoparticles with one or more magnetic elements for assembly into an antibacterial robot or autonomous magnetic bristles or robot suitable for removing dental biofilm, and applying a magnetic field along the surfaces of the upper teeth, lower teeth, including interdental and gingival, to move the antibacterial robot or autonomous magnetic bristles or robot to mechanically remove dental biofilm.

[0016] In certain embodiments, the suspension additionally includes a component selected from hydrogen peroxide, urea peroxide, enzymes, antibacterial compounds, surfactants, detergents, fluoride ion sources, abrasive compounds, glycerol, flavonoids, terpenes, polyphenols, proanthocyanidins, tannins, coumarin, rose bengal, perborate, metaperiodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof.

[0017] In certain embodiments, a method of removing dental biofilm includes inserting an oral care device of the present disclosure into a user's mouth, applying a suspension including iron oxide nanoparticles and hydrogen peroxide to the upper and lower channels. In certain embodiments, the suspension includes about 0.1% w / w to about 10% w / w, about 0.5% w / w to about 7.5% w / w, or 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 can include 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 can include 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 the hydrogen peroxide to generate biologically active free radicals capable of degrading and eradicating bacteria within the dental biofilm. The method further includes driving 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, and applying a magnetic field along the user's upper teeth, lower teeth, interdental spaces, and gum surfaces to move the antibacterial robot or autonomous magnetic bristles or robot to mechanically remove the dental biofilm. In certain embodiments, the suspension includes 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 water or water with 50% glycerol. In certain embodiments, the suspension includes 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 water or water with 50% glycerol.In certain embodiments, the suspension includes 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 water buffer. In one embodiment, the suspension includes 2000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol. In certain embodiments, the suspension includes one or more enzymes selected from the group consisting of allosteric enzymes, dextranases, and combinations thereof. In certain embodiments, the suspension includes 1% hydrogen peroxide and 1.75 U / 8.75 U allosteric enzyme / dextranase.

[0018] In certain embodiments, the present disclosure provides a method of detecting and removing dental biofilm, wherein the method includes inserting an oral care device of the present disclosure into a user's mouth, applying a suspension including iron oxide nanoparticles and hydrogen peroxide to the upper and lower channels. A portion of the iron oxide nanoparticles binds to the dental biofilm and another portion of the iron oxide nanoparticles remains unbound. The method further includes applying 3,3',5,5'-tetramethylbenzidine to the upper and lower channels to stain the biofilm-bound iron oxide nanoparticles blue; using a photodetector to locate the dental biofilm by detecting the bound iron oxide nanoparticles, using one or more magnetic elements to drive the unbound iron oxide nanoparticles to assemble into an antibacterial robot or autonomous magnetic bristles or robot suitable for removing the dental biofilm, and mechanically removing the dental biofilm by moving the antibacterial robot or autonomous magnetic bristles or robot along the surface having the bound iron oxide nanoparticles by applying a magnetic field. In certain embodiments, the method further includes detecting an amount of the dental biofilm removed.

[0019] In certain embodiments, the method of the present disclosure further includes monitoring a degree of plaque accumulation and a degree of plaque removal, the method including collecting data related to a location and amount of dental biofilm at a server, wherein the data is from detecting the bound iron oxide nanoparticles using a photodetector, converting the data into a numerical value representing the degree of plaque accumulation and the degree of plaque removal by a processor, and displaying a representation of the degree of plaque accumulation and the degree of plaque removal on a user interface of a terminal device or a web-based application. In certain embodiments, the representation of the degree of plaque accumulation and the degree of plaque removal is one or more of a numerical, graphical, or color / visual output.

[0020] The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate preferred embodiments of the application and serve to explain the principles of the application. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1Ais a schematic representation showing the dual catalytic-magnetic function of iron oxide nanoparticles.

[0022] Figure 1B is a schematic representation showing the resistance of biofilm to antimicrobial and mechanical removal due to EPS matrix.

[0023] Figure 1C is a schematic representation showing the detection and disruption of biofilm.

[0024] Figure 1D is a schematic representation showing the magnetic driving and biofilm removal.

[0025] Figure 2A Depicts a device made of flexible material that adapts to the dental arch. Close-up shows a multi-functional device with removal of dental biofilm and biofilm detection and monitoring.

[0026] Figure 2B Depicts a device wirelessly linked to an app / mobile device for monitoring oral health and hygiene (dental biofilm accumulation and removal).

[0027] Figure 3A Shows that iron oxide nanoparticles do not bind to epithelial cells of human gingiva.

[0028] Figure 3B Illustrates that iron oxide nanoparticles bind to biofilm.

[0029] Figure 3C Shows the efficacy of iron oxide nanoparticles to eradicate biofilm bacteria.

[0030] Figure 4A Depicts the relationship between iron oxide nanoparticle concentration and catalytic activity of iron oxide nanoparticles in biofilm. Figure 4A Inset further depicts the color change of biofilm (to blue) after iron oxide nanoparticle, TMB and hydrogen peroxide treatment.

[0031] Figure 4B Depicts the color change of biofilm (to blue) on real teeth after iron oxide nanoparticle, TMB and hydrogen peroxide treatment using an oral model. Figure 4B Further shows that TMB and hydrogen peroxide only stain the biofilm and not the teeth.

[0032] Figure 4C Shows a close-up of teeth with stained biofilm but no stained tooth surface.

[0033] Figure 5A Depicts a plaque detection circuit for detecting blue color.

[0034] Figure 5B Indicates that the indicator light LED of the plaque detection circuit is on when blue is detected.

[0035] Figure 5C Indicates that the indicator light LED of the plaque detection circuit is off when blue is not detected.

[0036] Figure 5D Indicates the amount of biofilm removed versus the blue indicator used for biofilm (plaque) detection.

[0037] Figures 6A to 6F Illustrates iron oxide nanoparticles being manipulated back and forth by a magnetic element.

[0038] Figure 7A Illustrates the bristle-like structure that iron oxide nanoparticles assume on the tooth surface in a magnetic field. Figure 7B The left side of illustrates the magnetic field off, Figure 7B The middle and right side of illustrates the collection of bristle-like structures showing after the magnetic field has just been turned on.

[0039] Figure 8A Illustrates the removal of plaque biofilm from the enamel surface by the magnetically controlled movement of the bristle-like iron oxide nanoparticle robotic structure.

[0040] Figure 9A Illustrates the removal of plaque biofilm from the interproximal area. DETAILED DESCRIPTION

[0041] The presently disclosed subject matter provides oral care devices that are capable of eradicating bacteria and degrading the biofilm matrix of plaque using a suspension containing iron oxide nanoparticles. In certain embodiments, the disclosed devices can also detect and monitor plaque. The disclosed devices can further include sensors and microprocessing features, such as Bluetooth, to allow real-time monitoring of the amount of plaque and removal of plaque. The disclosure also provides methods of eradicating bacteria and degrading the biofilm matrix of plaque using a suspension containing iron oxide nanoparticles, the suspension forming an antibacterial robot or autonomous magnetic bristle or robot.

[0042] For the sake of clarity, and not by way of limitation, the detailed description is divided into the following subsections:

[0043] Definitions

[0044] Iron nanoparticle suspension

[0045] Oral care device

[0046] Method of removing dental biofilm

[0047] Definitions

[0048] The terms used in the specification generally have their ordinary meanings in the context of the present subject matter and in the specific context of each term as used in the specific context. Certain terms are defined below to provide additional guidance to assist in the description of the compositions and methods of the disclosed subject matter and how to make and use them.

[0049] Unless the context clearly dictates otherwise, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents. Thus, for example, reference to "a compound" includes mixtures of compounds.

[0050] In the detailed description of embodiments herein, reference is made to "an embodiment," "one embodiment," "another embodiment," "some embodiments," and "other embodiments," which describe certain embodiments. However, the applications described herein can include a variety of embodiments, not necessarily all of which include the same features or characteristics. It is to be understood that where the description indicates there are alternatives for embodiments, each alternative is separately and individually an embodiment that can be described as being one of the alternatives. Furthermore, the use of "including," "having" "having at least" and "including at least" and "one or more of" are to be interpreted broadly to encompass terms such as "comprising" and / or "carrying." Moreover, the phrases "in one embodiment," "in another embodiment," "in some embodiments," and "in other embodiments" do not necessarily refer to the same embodiment, though they can. In addition, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the purview of one of ordinary skill in the art to effect such feature, structure, or characteristic in connection with other embodiments whether or not explicit description of the same is provided. It is intended to use such descriptors to attract the attention of those skilled in the art to the descriptions that follow and to assist in understanding the present disclosure.

[0051] The term "coupled" as used herein with respect to photodetectors and light emitting diodes means an electrical or wireless connection between two components, wherein the light emitting diode can produce a visual indicator of information detected by the photodetector.

[0052] The terms "dental biofilm" and "dental plaque" are used interchangeably herein to refer to a biofilm or bacterial mass that grows on surfaces within the oral cavity.

[0053] The term "user" as used herein includes mammals, such as animals or humans. In preferred embodiments, the subject is a human. In certain non-limiting embodiments, a "user" can be any individual who uses or interacts with a terminal device, which can use or interact with a user interface.

[0054] 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 can include a graphical user interface for displaying, to a user of the terminal device, but not limited to, graphical representations of plaque detection, plaque removal, and oral hygiene status. In certain embodiments, a web-based application can be installed on the user's terminal device. The user can monitor the progress of plaque removal using the web-based application.

[0055] "High frequency" as used herein refers to a frequency above 10 Hz.

[0056] Iron nanoparticle suspension

[0057] In certain embodiments, the iron oxide nanoparticles according to the disclosed subject matter are capable of mechanically removing plaque. Figure 6A It is shown that iron oxide nanoparticles can form clusters in a magnetic field, which are pulled along the surface, creating a controlled vortex motion. Figure 7A To D illustrates a different mechanism, where bristle-like structures are formed on the tooth surface in a magnetic field. As Figure 7A and 7B It is shown that by controlling the magnetic field direction and gradient, bristle-like structures of iron oxide nanoparticles are formed from the solution and extend to the enamel surface. Figure 7C It is further shown that the bristles of iron oxide nanoparticles can extend to a biofilm-covered surface and are driven laterally to sweep and remove the biofilm. Notably, as Figure 7D shown, the bristles of iron oxide nanoparticles conform to the changing surface profile while degrading and removing the biofilm.

[0058] In alternative embodiments, permanent magnets or electromagnets can be used while rotating, translating within the device, and vibrating.

[0059] In certain embodiments, the suspension of the present disclosure includes hydrogen peroxide in addition to the iron oxide nanoparticles. The iron oxide nanoparticles activate the hydrogen peroxide to generate bioactive radicals capable of degrading and eradicating bacteria within the dental biofilm. In particular, the iron oxide nanoparticles catalyze the decomposition of hydrogen peroxide to generate radicals, such as HO· and HO2· radicals. Figure 1A and 1BThe dual catalytic-magnetic functionality of iron oxide nanoparticles according to embodiments of the disclosed subject matter is shown. Iron oxide nanoparticles can catalyze hydrogen peroxide (H2O2) to substantially eradicate bacteria and degrade biofilm matrix. Biofilm matrix degradation is key to disrupting the scaffold while also aiding in penetration and bacterial eradication. When degrading biofilm matrix, bacterial eradication is greatly enhanced. When biofilm matrix is sufficiently broken down to allow substantial bacterial eradication (>99.999% kill), the biofilm is degraded. Iron oxide nanoparticles can be magnetically activated to drive the iron oxide nanoparticles to assemble into an antibacterial robot or autonomous magnetic bristle or robot, and move the antibacterial robot or autonomous magnetic bristle or robot to remove biofilm debris.

[0060] Figure 1C and 1D The conceptual framework of a plaque removal and detection system using catalytic antibacterial robots is shown. In Figure 1C , iron oxide nanoparticles bind to and penetrate the biofilm and catalyze H2O2 in situ to break down the biofilm matrix and kill bacteria. At the same time, the nanoparticles can react with TMB during the catalysis (see claim

[0011] ) to produce blue as an indicator of plaque (biofilm), thus as a detector of biofilm accumulation. When the nanoparticles are driven by a magnetic field ( Figure 1D left), it aggregates and assembles into a bristle-like structure that removes and brushes away the biofilm ( Figure 1D right); importantly, these nanoparticles do not bind to the tooth or mucosal surface. Since these biofilms can also be marked with blue (see above), the amount of plaque removal can also be measured, thus serving as a plaque removal detection.

[0061] In certain embodiments, the suspension of the present disclosure includes a peroxidase- sensitive dye in addition to the iron oxide nanoparticles and hydrogen peroxide. In particular embodiments, the peroxidase-sensitive dye is 3,3',5,5'-tetramethylbenzidine.Other dyes include: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic 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, and fluorescent dyes including 10-Acetyl-3,7-dihydroxyphenoxazine, Terephthalic acid, Homovanillic acid, 2-[6-(4-aminophenoxy)-3-oxo-3H-xanthen-9-yl]-benzoic acid, (2-[6-(4'-hydroxy)phenoxy-3H-xanthene-3-on-9-yl]benzoic acid, 2',7'-Dichlorofluorescein diacetate, 2,7-Dichlorodihydrofluorescein diacetate, Coumarin Boronic Acid, Coumarin Boronic Acid pinacolate ester, Dihydrorhodamine 123, Lucigenin, Dihydroethidium. Iron oxide nanoparticles are able to bind to dental biofilm and in the presence of hydrogen peroxide and peroxidase sensitive dyes produce a colour that can be used to detect dental plaque.

[0062] The suspension comprising iron oxide particles can further include one or more enzymes, such as mutanase or dextranase, to further assist in degrading the biofilm matrix. In certain embodiments, the suspension can be formulated with 1% hydrogen peroxide and 1.75 U / 8.75 U mutanase / dextranase to substantially eradicate bacteria and degrade the biofilm matrix. Figure 3C To demonstrate efficacy of biofilm eradication of a suspension comprising iron oxide nanoparticles, hydrogen peroxide, and mutanase / dextranase.

[0063] In certain embodiments, the suspension comprising iron oxide nanoparticles includes glycerol and / or water, or an aqueous buffer. In certain embodiments, the suspension includes from about 500 micrograms to about 5000 micrograms, from about 750 micrograms to about 4750 micrograms, from about 1000 micrograms to about 4500 micrograms, from about 1250 micrograms to about 4250 micrograms, from about 1500 micrograms to about 4000 micrograms, from about 1750 micrograms to about 3750 micrograms, or from about 2000 micrograms to about 3500 micrograms of iron oxide nanoparticles per milliliter of water with 50% glycerol, or water, or an aqueous buffer. In certain embodiments, the suspension includes 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 water with 50% glycerol, or water. In certain embodiments, the suspension includes 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 water with 50% glycerol, or water. In one embodiment, the suspension includes 2000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol.

[0064] In certain embodiments, the suspension comprising iron oxide nanoparticles can include other components commonly used in oral care compositions, such as, but not limited to, carbamide peroxide, antibacterial compounds, fluoride ion sources, abrasive compounds, surfactants, detergents, enzymes, and combinations thereof. Non-limiting examples of antibacterial compounds include triclosan, essential oils, terpenoids, flavonoids, polyphenols, proanthocyanidins, tannins, coumarin, chlorhexidine, antimicrobial peptides, arginine. Non-limiting examples of enzymes include dextranase, allosteric enzymes, lipase, deoxyribonuclease, 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.

[0065] Oral care device

[0066] The device of the present disclosure is configured to bring the suspension comprising iron oxide nanoparticles into contact with the surfaces of the user's teeth and gums. In certain embodiments, the oral care device of the present disclosure comprises a flexible mouthpiece comprising an upper channel to fit over the user's upper teeth and a lower channel to fit over the user's lower teeth. The dimensions of the mouthpiece can be suitable for the typical human range from children to adults. The range of an adult's mouth opening is 30-70 mm, and the range of an adult's total dental arch length is 35-45 mm. In certain embodiments, the dimensions of the mouthpiece are adjustable. Figure 2A and 2B Non-limiting examples of mouthpieces are provided. Specifically, Figure 2A An exemplary flexible mouthpiece is represented, comprising an upper channel, a lower channel that can accommodate the dental arch. Close-up views represent the device placed with magnetic control bristles that break up plaque, means to monitor plaque in real time, and means to provide vibrational action.

[0067] Figure 2B A device is depicted wirelessly linked to an app / mobile device for monitoring oral health and hygiene (dental biofilm accumulation and removal).

[0068] In certain embodiments, the mouthpiece of the present disclosure includes one or more magnetic elements to generate a magnetic field. Non-limiting examples of magnetic elements include electromagnets, which include a magnetic core that can concentrate and amplify the pull force. In certain embodiments, the magnetic gradient generated by these magnets can range from about 0.01 mT / mm to about 200 mT / mm, from about 1 mT / mm to about 180 mT / mm, from about 25 mT / mm to about 150 mT / mm, or from about 50 mT / mm to about 100 mT / mm. In certain embodiments, the magnetic gradient generated by these magnets is at least 1 mT / mm, at least 10 mT / mm, at least 25 mT / mm, at least 50 mT / mm, at least 75 mT / mm, at least 100 mT / mm, at least 125 mT / mm, at least 150 mT / mm, or at least 175 mT / mm. In certain embodiments, the maximum gradient is no more than 200 mT / mm. The frequency at which switching of the magnetic field can occur ranges, but is not limited to, values from about 0.2 Hz to about 100 Hz, from about 5 Hz to about 75 Hz, from about 20 Hz to about 60 Hz, from about 30 Hz to about 50 Hz. In certain embodiments, the magnetic field is generated by permanent magnets, such as, but not limited to, iron, iron-nickel alloys, neodymium iron boron, and samarium cobalt.

[0069] In certain embodiments, the oral care device includes one or more haptic drivers (e.g., vibration drivers). In certain embodiments, the drivers used herein are small oscillating devices (motors or piezoelectric material) that generate vibrations that can be felt (haptic), and can additionally re-suspend nanoparticles and / or aid in biofilm removal. Non-limiting examples of vibration drivers include rotating motors with unbalanced masses that can be activated and varied in terms of vibration frequency and amplitude. In certain embodiments, the one or more vibration drivers are vibration motors. Non-limiting commercial embodiments of vibration drivers include the Z7AL2B1690002 by Jinlong Machinery & Electronics, Inc. In certain embodiments, the vibration frequency varies from about 10 Hz to about 20,000 Hz. In certain non-limiting embodiments, the vibration action is caused by high frequency magnetic motion, where an electromagnet and / or piezoelectric driver delivers iron oxide nanoparticles through high frequency oscillation 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.

[0070] In certain embodiments, the oral care device of the present disclosure further includes a photodetector or a red-green-blue (RGB) sensor. In certain embodiments, the photodetector or RGB sensor is coupled with 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 Figure 5A .Figure 5A Circuit 500 is depicted for detecting blue in tray 502. Circuit 500 includes light emitting diode 504 and photodetector 506. Figure 5B and 5C Indicates that indicator light emitting diode 504 turns on when photodetector 506 detects blue light in tray 502, and remains off when no blue is detected.

[0071] The oral care device of the present disclosure can accommodate a battery and power electronics in its size. In certain embodiments, the oral care device further comprises microprocessing capabilities.

[0072] In certain embodiments, the oral care device can be wirelessly connected to another device to monitor removal of dental biofilm in real time.

[0073] Method of detecting and removing dental plaque

[0074] The present disclosure is also about a method of removing dental plaque using the oral care device described herein. In certain embodiments, a user can remove dental plaque by applying a suspension comprising iron oxide nanoparticles disclosed herein to the upper and lower channels of the mouthpiece and mounting the mouthpiece on the upper and lower teeth. Upon turning on the device, the iron oxide nanoparticles move due to the magnetic field and / or the vibrating action, forming an antibacterial robot or autonomous magnetic bristle or robot, thereby mechanically removing the dental plaque.

[0075] In certain embodiments, dental plaque can be removed by applying a suspension comprising iron oxide nanoparticles and hydrogen peroxide to the upper and lower channels of the mouthpiece and mounting the mouthpiece on the upper and lower teeth. The iron oxide nanoparticles catalyze the decomposition of hydrogen peroxide to produce HO· and HO2· radicals, which in turn eradicate bacteria within the biofilm and degrade the biofilm. Furthermore, upon turning on the device, the iron oxide nanoparticles move due to the magnetic field and / or the vibrating action, thereby mechanically removing the dental plaque.

[0076] In certain embodiments, dental plaque can be detected and removed by applying a suspension comprising iron oxide nanoparticles, hydrogen peroxide, and a peroxide enzyme-sensitive stain to the upper and lower channels of the mouthpiece and mounting the mouthpiece on the upper and lower teeth. A portion of the iron oxide nanoparticles binds to the dental plaque. The suspension further stains the dental plaque blue with the bound iron oxide particles, without staining the teeth, thereby serving as a dental plaque detection, as shown in Figures 4A-4C A visual indicator can further be used to identify the location of the dental plaque, followed by directing the unbound iron oxide nanoparticles to the dental plaque in the direction of the stained dental plaque, to mechanically remove it. Furthermore, since the biofilm is stained blue, the amount of dental plaque removal can also be measured, thereby serving as a dental plaque (biofilm) removal detection.

[0077] Figure 8A To D further demonstrates the ability of the antibacterial robot or autonomous magnetic bristles or robot to remove plaque from the teeth. Figure 8A and 8C An image of the "before" showing the pink-stained biofilm formed on the tooth block, Figure 8B and 8D An "after image" is provided showing the same tooth block after automatic cleaning by the autonomous magnetic bristles or robot, demonstrating complete removal of the biofilm.

[0078] Figure 9A To C further demonstrates the ability of the antibacterial robot or autonomous magnetic bristles or robot to remove plaque from a narrow area, for example, such as the area between teeth. This cleaning is performed by driving the collection of iron oxide nanoparticles in a reciprocating motion through the interproximal space. Figure 9B An image of the "before" is provided showing plaque in the narrow area between the two "model teeth", Figure 9C An image of the "after" is provided showing that the plaque at the interproximal area has been removed; a close-up view demonstrates complete removal of the biofilm in the narrow space between the teeth.

[0079] In certain embodiments, the level of plaque accumulation and the level of plaque removal can be monitored and / or visualized on a network-based application on or in the end device. Once the photodetector or RGB sensor obtains data about the plaque and its quantity, this data can be transmitted for real-time monitoring and stored to a storage device located outside the sensor. A given sensor can transmit the obtained data to a server, which can then collect data related to the quantity of plaque and its location as well as plaque removal. In certain non-limiting embodiments, a centralized server can collect all data, while in other non-limiting embodiments, the collection of data can be distributed to multiple servers. Each server can include one or more databases that store the collected information. When a centralized server collects all data, the data can be saved in one database, or in multiple databases. The databases can include tags or identifiers that describe the characteristics of the collected data, such as the type of data collected. In certain embodiments, the data can be converted into a numerical value by a processor, which numerical value indicates the level of accumulation of plaque and the level of removal of plaque. In certain embodiments, a range of colors can be used to visualize the results. In certain embodiments, the collected data can be used to monitor the oral hygiene and oral health status over an extended period of time. In certain embodiments, the network-based application or end device can be used to monitor real-time removal of plaque and real-time monitoring of the amount of plaque accumulation on the teeth.

[0080] The foregoing merely illustrates the principles of the disclosed subject matter. It will thus be appreciated that those skilled in the art will be able to devise various arrangements that, although not explicitly described or shown herein, embody the principles of the disclosed subject matter and are thus within its spirit and scope.

Claims

1. An oral care device comprising: a flexible mouthpiece having an upper channel to fit over the upper teeth, a lower channel to fit over the lower teeth of a user, and a photodetector or RGB sensor for obtaining data about dental plaque and its quantity; wherein the mouthpiece further comprises: a suspension comprising iron oxide nanoparticles, one or more magnetic elements adapted to apply a magnetic field, wherein the iron oxide nanoparticles are configured to form clusters that are pulled along the tooth surface, creating a controlled vortex motion, thereby forming a bristle-like structure by controlling the magnetic field, and a vibrating motor to additionally resuspend the nanoparticles.

2. The oral care device of claim 1, wherein the one or more magnetic elements comprise a permanent magnet or an electromagnet adapted to apply a magnetic field to the biofilm to drive the iron oxide nanoparticles to assemble into antibacterial robots or autonomous magnetic bristles or robots suitable for removing dental biofilm.

3. The device of claim 1, wherein the photodetector is coupled with a light emitting diode.

4. The device of claim 1, wherein the mouthpiece is to provide contact between the suspension and the surfaces of the upper teeth, lower teeth, including interdental spaces, and gums of a user.

5. The device of claim 4, wherein the suspension further comprises a component selected from the group consisting of: hydrogen peroxide, urea peroxide, one or more enzymes, one or more antibacterial compounds, one or more surfactants, one or more detergents, one or more fluoride ion sources, one or more abrasive compounds, glycerol, one or more flavonoids, terpenes, polyphenols, proanthocyanidins, tannins, coumarin, rose bengal, perborate, metaperiodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof.

6. The device of claim 5, wherein the suspension comprises hydrogen peroxide.

7. The device of claim 5, wherein the suspension comprises one or more enzymes.

8. The apparatus of claim 7, wherein, the one or more enzymes are allosteric enzymes, dextranases, deoxyribonuclease DNases, proteases, lipases, amyloglucosidases, glucose oxidases, or combinations thereof.

9. The apparatus of claim 6, wherein, the suspension further comprises a peroxidase-sensitive dye.

10. The device of claim 1, wherein the device is configured to perform the following processes: inserting the device into the mouth of a user; applying a suspension comprising iron oxide nanoparticles to the upper and lower channels of the mouthpiece, driving the iron oxide nanoparticles with one or more magnetic elements to assemble into antibacterial robots or autonomous magnetic bristles or robots suitable for removing dental biofilm; applying a magnetic field to move the antibacterial robots or autonomous magnetic bristles or robots along the surfaces of the upper teeth, lower teeth, including interdental spaces, and gums of a user to mechanically remove dental biofilm; and obtaining data about dental plaque and its quantity.

11. The device of claim 10, wherein the suspension further comprises a component selected from the group consisting of: hydrogen peroxide, urea peroxide, one or more enzymes, one or more antibacterial compounds, one or more fluoride ion sources, one or more abrasive compounds, glycerol, surfactants, detergents, flavonoids, terpenes, polyphenols, proanthocyanidins, tannins, coumarin, rose bengal, perborate, metaperiodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof.

12. The device of claim 11, wherein the suspension comprises hydrogen peroxide, and wherein the iron oxide nanoparticles activate the hydrogen peroxide to generate free radicals capable of degrading and eradicating bacteria within the dental biofilm.

13. The device of claim 10, wherein the suspension comprises 2000 micrograms of iron oxide nanoparticles in 50% glycerol or aqueous buffer per milliliter.

14. The device of claim 11, wherein the suspension comprises one or more enzymes selected from the group consisting of allosteric enzymes, dextranases, and combinations thereof.

15. The device of claim 11, wherein the suspension comprises 1% H2O2 and 1.75 U / 8.75 U allosteric enzyme / dextranase.

16. The device of claim 1, wherein the device is configured to perform the following processes: inserting the device into a user’s mouth; applying a suspension comprising iron oxide nanoparticles and hydrogen peroxide to the upper and lower channels of the mouthpiece, wherein a portion of the iron oxide nanoparticles bind to the dental biofilm and the remainder of the iron oxide nanoparticles remain unbound, applying 3,3',5,5'-tetramethylbenzidine to the upper and lower channels of the mouthpiece, dyeing the bound iron oxide nanoparticles blue, localizing the dental biofilm by detecting the bound iron oxide nanoparticles with a photodetector; driving the unbound iron oxide nanoparticles with the one or more magnetic elements to assemble into an antibacterial robot or autonomous magnetic bristle or robot suitable for removing the dental biofilm; and mechanically removing the dental biofilm by moving the antibacterial robot or autonomous magnetic bristle or robot along the surfaces of the user’s upper teeth, lower teeth, interdental spaces, and gums by applying a magnetic field.

17. The device of claim 16, wherein the processes further comprise detecting the amount of the dental biofilm removed.

18. The device of claim 16, wherein the processes further comprise monitoring the degree of plaque accumulation and the degree of plaque removal, the processes comprising: collecting data related to the location and amount of dental biofilm at a server, wherein the data is from detecting the bound iron oxide nanoparticles with a photodetector; converting the data into numerical values representing the degree of plaque accumulation and the degree of plaque removal by a processor; and displaying a representation of the degree of plaque accumulation and the degree of plaque removal on a user interface of a terminal device or a web-based application. ​ ​ 19. The apparatus of claim 18, wherein the representation of the degree of plaque accumulation and the degree of plaque removal is one or more of a numerical, graphical, or color / visual output.

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