WO2020100070A1

WO2020100070A1 - Biochemical dental instrument for detecting caries

Info

Publication number: WO2020100070A1
Application number: PCT/IB2019/059761
Authority: WO
Inventors: Rudolf Schmid; Ingo R. Haeberlein
Original assignee: 3M Innovative Properties Company
Priority date: 2018-11-13
Filing date: 2019-11-13
Publication date: 2020-05-22

Abstract

Dental instruments having a lactate biosensor for detecting caries activities at site-specific tooth surface locales, and methods thereof, are described.

Description

BIOCHEMICAL DENTAL INSTRUMENT FOR DETECTING CARIES

BACKGROUND

[0001] Dental caries results from an imbalance of the metabolic activity in dental biofilm (Nyvad, et al. Caries Research 2013, 47, 89-102). The presence of bacteria alone cannot necessarily indicate imbalanced metabolic activity, as it is common experience in clinical settings to observe patients with increased plaque without having greater caries risk (Nascimento, et al. J. Dent. Res. 2017, 96, 733-740). In other words, many of the biofilms in an individuaTs mouth are harmless, whereas others cause demineralization. There is currently no convenient method for detecting site- specific dental biofilms that lead to demineralization.

[0002] Present methods for detecting carious lesions involve locating sites of demineralization and are divided into two categories— physical and chemical.

[0003] Physical caries detection methods include, for example, X-rays, laser-enhanced fluorescence, trans-illumination with fiber optics, and electrical conductivity. Such methods are often time-consuming and require expensive auxiliary equipment.

[0004] Chemical caries detection methods include, for example, applying a dye configured to adhere to carious lesions. Such methods are effective for detecting caries in enamel but are ineffective for detecting caries in underlying dentin.

[0005] The physical and chemical procedures described cannot immediately detect whether caries processes are still active or arrested. Moreover, such procedures cannot differentiate between infected (non-remineralizable) and affected tooth tissue (remineralizable), which can lead to over excavation of otherwise salvageable tooth tissue.

[0006] What is needed are instruments and methods for site-specific detection of active caries processes.

SUMMARY

[0007] In one embodiment, a dental instrument for use in detecting caries activity at a site- specific locale of a tooth surface is described. The dental instrument may include a lactate biosensor and an evaluation meter. The lactate biosensor may include an elongated shaft having a first end and a second end opposite the first end; an intra-oral tip at the first end and having an inlet channel for receiving a liquid sample from the tooth surface; a chamber; an enzymatic matrix; a working electrode; a counter electrode; an electrical interface at the second end and electrically connected to the working electrode and the counter electrode; and a venting channel extending along at least a portion of the elongated shaft and terminating at the second end at a vent opening. The inlet channel, the enzymatic matrix, the working electrode, the counter electrode, and the venting channel may be in fluid communication with the chamber. The lactate biosensor may generate an electrical output based on an interaction between the liquid sample and the enzymatic matrix. The evaluation meter may be electrically connected to the lactate biosensor and may detect and transform the electrical output to provide a signal indicating a degree of caries activity.

[0008] In one embodiment, a lactate biosensor for use in detecting caries activity at a site- specific locale of a tooth surface is described. The lactate biosensor may include an elongated shaft having a first end and a second end opposite the first end; an intra-oral tip at the first end and having an inlet channel for receiving a liquid sample from the tooth surface; a chamber; an enzymatic matrix; a working electrode; a counter electrode; an electrical interface at the second end and electrically connected to the working electrode and the counter electrode; and a venting channel extending along at least a portion of the elongated shaft and terminating at the second end at a vent opening. The inlet channel, the enzymatic matrix, the working electrode, the counter electrode, and the venting channel may be in fluid communication with the chamber. The lactate biosensor may generate an electrical output based on an interaction between the liquid sample and the enzymatic matrix.

[0009] In one embodiment, a method of detecting caries activity at a site-specific locale on a tooth surface is described. The method may include providing a dental instrument described herein. The method may include applying a sugar composition to the site-specific locale and allowing the sugar composition to interact with bacteria at the site-specific locale to form a liquid sample. The method may include withdrawing at least a portion of the liquid sample with the dental instrument and subjecting the liquid sample to a lactate measurement. The method may include determining a degree of caries activity according to a lactate measurement value.

[0010] In on embodiment, a kit is described. The kit may include a dental instrument described herein, a sugar composition described herein, and a set of instructions directing a user to carry out a method described herein.

[0011] In various embodiments, a kit is described. The kit may include a lactate biosensor described herein, a sugar composition described herein, and a set of instructions directing a user to apply the sugar composition to a site-specific locale; allow the sugar composition to interact with bacteria at the site -specific locale to form a liquid sample; withdraw at least a portion of the liquid sample; subject the liquid sample to a lactate measurement; and determine a degree of caries activity according to a lactate measurement value. BRIEF DESCRIPTION OF DRAWINGS

[0012] FIG. 1A is a perspective view of a lactate biosensor of the present disclosure.

[0013] FIG. IB is a perspective view of a lactate biosensor in an inclined position.

[0014] FIG. 1C is a perspective view of a lactate biosensor of the present disclosure.

[0015] FIG. ID is a perspective view of a lactate biosensor of the present disclosure in use.

[0016] FIG. 2 is a perspective view of a lactate biosensor of the present disclosure.

[0017] FIG. 3 is a perspective view of a lactate biosensor of the present disclosure.

[0018] FIG. 4A is a perspective view of a dental instrument of the present disclosure.

[0019] FIG. 4B is an expanded view of the dental instrument of FIG. 4A.

[0020] FIG. 5 is a perspective view of a dental instrument of the present disclosure.

[0021] FIG. 6 is a perspective view of a dental instrument of the present disclosure.

[0022] FIG. 7 is a flow diagram illustrating a method of the present disclosure.

[0023] FIG. 8 illustrates a kit of the present disclosure.

[0024] FIG. 9 illustrates a kit of the present disclosure.

DETAILED DESCRIPTION

[0025] Certain bacteria or certain groups of bacteria ferment sugars to produce acidic components, such as lactic acid. Lactic acid may dissolve calcium phosphate in tooth enamel, i.e., demineralize tooth enamel, causing caries. Multiple site-specific lactic acid measurements may allow for the identification of caries activity and the degree of such activity over the entire tooth landscape.

[0026] The present disclosure describes tools and techniques for monitoring the activities of bacterial biofilms on teeth by quantifying lactic acid production in response to applied sugar compositions. Having a convenient way to assess dental biofilm activities may offer guidance for individualized preventative care recommendations, as well as aiding diagnostic and restorative efforts.

[0027] Principles of determining the risk of caries in view of lactic acid and/or lactate are disclosed in U.S. Patent Application Publication No. U.S. 2004/0141960 Al,“Determining the Risk of Caries in a Patient,” Haberlein et al., which is hereby incorporated by reference herein. Current tests indicate that tooth demineralization occurs at lactic acid concentrations at or above 3 mM.

[0028] The present disclosure describes tools and techniques for measuring lactate concentrations in a range of about 1 to about 20 mM.

[0029] As used herein,“about” means ±10% of a stated value. For example, about 10 means 9 to 11. [0030] As used herein,“bacteria” refer to bacteria that ferment sugars into acids, e.g., lactic acid.

[0031] As used herein,“caries activity” means lactic acid is detectable with the biosensors and instruments described herein. Further,

[0032] As used herein,“a degree of caries activity” means the severity of caries activity based on the concentration of lactic acid measured. The degree of caries activity may be quantitative, e.g., a percentage above a caries activity threshold. Alternatively, the degree of caries activity may indicate whether a site-specific locale is at or above a caries activity threshold. A user may determine appropriate further action based on the degree of caries activity measured, e.g., monitoring; treating (e.g., remineralization); restoring, or the like.

[0033] As used herein,“caries activity threshold” refers to a value of a lactic acid concentration detected at 3mM or above. Current scientific and clinical tests indicate that lactic acid concentrations above 3mM may initiate tooth demineralization; however, this diagnostic threshold is subject to change. The current tools and techniques of the present disclosure may sense lactic acid concentrations as low as 1 mM.

[0034] As used herein, the phrase“inclined position” refers to a portion being out of a plane defined by a longitudinal axis A at an angle Q (e.g., see FIG. IB).

[0035] As used herein, a“subject” refers to a human or animal having teeth.

[0036] As used herein, “lactic acid,” “lactate,” and “lactate/lactic acid” are used interchangeably and are meant to define the bacterial byproduct of sugar fermentation.

[0037] As used herein,“liquid sample” refers to a mixture resulting from contacting a sugar composition with a site-specific locale tooth surface. The liquid sample may include fermentation byproducts from bacterial sugar consumption, e.g., lactic acid.

[0038] As used herein, “sugar composition” refers to a sugar or combination of sugars dissolved, suspended, or dispersed within a medium.

[0039] As used herein,“site-specific locale” refers to an area of about 0.5 mm² to about 1 mm². For example, the area may be in mm² of about 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0, or a value in a range between any of the preceding values, for example, between about 0.5 mm² and about 0.7 mm², between about 0.8 mm² and about 1.0 mm², or the like.

[0040] FIG. 1 A illustrates one embodiment of a lactate biosensor 100 of the present disclosure .

Lactate biosensor 100 is defined by first end 102 and a second end 104 and an elongated shaft 106 extending between first end 102 and second end 104.

[0041] Lactate biosensor 100 includes an intra-oral tip 108 at first end 102 and an electrical interface 110 at second end 104. [0042] Intra-oral tip 108 includes a counter electrode 112, a working electrode 114, and a reference electrode 116. Each electrode is contact with an electrically conductive track 118a, 118b, or 118c, respectively, that extend along shaft 106. Each electrically conductive track terminates at electrical interface 110. Electrical interface 110 includes a first electrical contact pad 120, a second electrical contact pad 122, and a third electrical contact pad 124. Electrical interface 110 is configured to be or become in electrical communication with an evaluation meter (not shown).

[0043] Intra-oral tip 108 includes a nozzle inlet 126, which in includes an inlet opening 128 for receiving a liquid sample (or saliva). Intra-oral tip 108 may further include a chamber 130 in fluid communication with inlet opening 128 via an inlet channel 129. Chamber 130 spans counter electrode 112, working electrode 114, and reference electrode 116. Chamber 130 is configured to absorb a liquid sample (or saliva) from inlet opening 128 through capillary action within inlet channel 129. An enzymatic matrix (not shown) is housed within an enzymatic reservoir 131 that is in fluid communication with chamber 130 via inlet channel 129 such that the liquid sample may interact with the enzymatic matrix.

[0044] Lactate biosensor 100 further includes a venting channel 133. Venting channel 133 extends along at least a portion of elongated shaft 106 and is in communication with chamber 130 and/or enzymatic reservoir 131. Venting channel 133 includes a vent opening 135 near second 104 and is configured to connect to a vacuum source (not shown).

[0045] Intra-oral tip 108 further includes notches 132a and 132b to facilitate bending of intra oral tip 108 into an inclined position relative to longitudinal axis A (see FIG. IB).

[0046] FIG. IB illustrates lactate biosensor 100 of the present disclosure with intra-oral tip 108 in an inclined position with respect to a longitudinal axis A that is parallel to elongated shaft 106.

[0047] FIG. 1C illustrates lactate biosensor 100 further including a break strip 134 connected to electrical interface 110. Lactate biosensor 100 further includes a break zone 136 between electrical interface 110 and break strip 134. A user may use break strip 134 as a handle. Lactate biosensor 100 having break strip 134 may be considered a dental instrument.

[0048] FIG. ID illustrates lactate biosensor 100 in use with a tooth surface 138. As shown, intra-oral tip 108 is in an inclined position. Lactate biosensor 100 is further shown having a nozzle jacket 140. Nozzle jacket 140 includes a nozzle 142. Nozzle jacket 140 may be configured to deliver a composition to tooth surface 138 and/or extract a liquid sample from tooth surface 138.

[0049] FIG. 2 illustrates a lactate biosensor 200 further including a channel housing 244 for housing a channel (not shown) and a reservoir 246. Lactate biosensor 200 includes all features described in FIGs. 1A-1D, including those numbered accordingly. Reservoir 246 is filled with a gas, e.g., air. Pressing and releasing reservoir 246 affords a suctioning effect (vacuum) that allows for liquids with higher viscosities to be withdrawn into the inlet channel 229. [0050] FIG. 3 illustrates a lactate biosensor 300 further including a pipette 348 and reservoir 350. Lactate biosensor 300 includes all features described in FIGs. 1A-1D, including those numbered accordingly. Reservoir 350 has one or more compartments. Each compartment may independently be fdled with gas, e.g., air, a sugar composition, or a cleaning composition. Each compartment in reservoir 350 may be connected to a channel within pipette 348.

[0051] FIG. 4A illustrates a dental instrument 401 having a lactate biosensor 400. Lactate biosensor 400 may include all the features described in FIGs. 1A, IB, and ID, including those numbered accordingly. Dental instrument 401 includes a handle 452. Handle 452 includes a receiving slot 454 configured to electrically accept lactate biosensor 400. Receiving slot 454 further includes a retention spring 456 for securing lactate biosensor 400 within receiving slot 454.

[0052] FIG. 4B illustrates an expanded view of receiving slot 454 and retention spring 456 in dental instrument 401.

[0053] FIG. 5 illustrates a dental instrument 501 having a lactate biosensor 500. Lactate biosensor 500 may include all the features described in FIGs. 1A, IB, ID, 2, and 3, including those numbered accordingly. Dental instrument 501 may include handle 552. Handle 552 houses an evaluation meter (not shown). Handle 552 includes status indicators 558a and 558b which may indicate the presence or absence of caries. Handle 552 includes an activation button 560. Compressing activation button 560 may turn on the device. Compressing activation button 560 may expel air, expel a sugar composition, expel a cleaning composition, or a combination thereof, from a reservoir such as those illustrated in FIGs. 2-3. Handle 552 includes status indicators 558a and 558b which may indicate the presence or absence of caries. For example, status indicator 561a may light up if the lactate concentration is measured above a caries activity threshold, and status indicator 561b may light up if the lactate concentration is below the caries activity threshold. Dental instrument 501 further includes a battery (not shown).

[0054] FIG. 6 illustrates a dental instrument 601 having lactate biosensor 600. Lactate biosensor 600 may include all the features described in FIGs. 1A, IB, ID, 2, 3, and 5, including those numbered accordingly. Dental instrument 601 further includes a display window 662. Display window 662 is configured to indicate a color or alpha-numeric value representing the level of caries activity.

[0055] FIG. 7 illustrates a flow diagram illustrating a method 703 of the present disclosure. Method 703 includes 764 providing a dental instrument of the present disclosure, 766 applying a sugar composition to a site-specific locale on a tooth surface of a subject, 768 allowing the sugar composition to interact with bacteria on the tooth surface at the site-specific locale to form a liquid sample, 770 withdrawing at least a portion of the liquid sample from the tooth surface with at least a portion of dental instrument, 772 subjecting the liquid sample to a lactate measurement, and 774 determining a degree of caries activity according to the lactate measurement value.

[0056] FIG. 8 illustrates a kit 805 of the present disclosure. Kit 805 includes a lactate biosensor

800 described herein, a sugar composition 876, and a set of instructions 878 directing a user to apply sugar composition 876 to a site-specific tooth surface locale to form a liquid sample and withdraw at least a portion of the liquid sample with the lactate biosensor 800.

[0057] FIG. 9 illustrates a kit 905 of the present disclosure. Kit 905 includes a dental instrument 901 described herein, a sugar composition 976, and a set of instructions 978 directing a user to perform a method described herein.

Lactate Biosensor

[0058] In one embodiment, a lactate biosensor for use in detecting caries activity at a site- specific locale of a tooth surface is described. The lactate biosensor may include an elongated shaft having a first end and a second end opposite the first end; an intra-oral tip at the first end and having an inlet channel for receiving a liquid sample from the tooth surface; a chamber; an enzymatic matrix; a working electrode; a counter electrode; an electrical interface at the second end and electrically connected to the working electrode and the counter electrode; and a venting channel extending along at least a portion of the elongated shaft and terminating at the second end at a vent opening. The inlet channel, the enzymatic matrix, the working electrode, the counter electrode, and the venting channel may be in fluid communication with the chamber. The lactate biosensor may generate an electrical output based on an interaction between the liquid sample and the enzymatic matrix.

[0059] In many embodiments, the lactate biosensor may include an intra-oral tip housing a nozzle inlet. In many embodiments, the nozzle inlet may lead to an inlet channel. The inlet channel may include an inlet opening for receiving a liquid sample (or saliva). In some embodiments, the chamber may be in fluid communication with inlet opening via the inlet channel. The chamber may be configured to absorb a liquid sample (or saliva) from the inlet opening through capillary action within the inlet channel.

[0060] In some embodiments, the chamber may further include a sugar composition such that a saliva and/or liquid sample withdrawn from a tooth surface may be mixed or further mixed with the sugar composition within the chamber.

[0061] In several embodiments, the inlet channel may have a cylinder shape.

[0062] In many embodiments, the inlet channel may have an inner diameter of about 0.1 mm to about 0.5 mm. For example, the inlet channel may have an inner diameter in mm of about 0.1, 0.2, 0.3, 0.4, or 0.5, or a value within a range between any of the preceding values, for example, between about 0.2 and about 0.3, between about 0.1 and about 0.3, or the like.

[0063] In many embodiments, the inlet channel may have a length of about 2 mm to about 20 mm. For example, the inlet channel may have a length in mm of about 2, 4, 6, 8, 10, 12, 14, 16, 18, or 20, or a value within a range between any of the preceding values, for example, between about 4 and about 14, between about 5 and about 10, or the like. In some embodiments, the inlet channel is about 5 mm to about 7 mm in length.

[0064] In many embodiments, the amount of liquid sample to be extracted from a site-specific tooth surface locale may be between about 0.2 pL and about 5 pL. For example, the amount of liquid sample to be extracted may be in pL of about 0.2, 0.5, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.2., 2.4, 2.6, 2.8, 3.0, 3.5, 4.0, 4.5, and 5.0, or a values within a range between any of the preceding values, for example, between about 2.0 pL and about 2.6 pL, between about 1.2 pL and about 3.0 pL, or the like. In some embodiments, the amount of liquid sample to be extracted is about 1 pL to about 2 pL.

[0065] In some embodiments, the inlet channel may include a wicking material. The wicking material may be an absorbent filament, nonwoven, or porous material. In some embodiments, the wicking material may be coated with a wick-enhancing coating. The wicking material may aid in the absorption of the liquid sample into the lactate biosensor.

[0066] In some embodiments, the intra-oral tip may include a counter electrode and a working electrode. In other embodiments, the intra-oral tip may also further include a reference electrode. Each of the counter, working, and/or reference electrode may be in contact with an electrically conductive track. In some embodiments, each of the conductive tracks may extend along the shaft. Each conductive track may terminate at the electrical interface. The electrical interface may include a first electrical contact pad and a second electrical contact pad. If a lactate biosensor has a reference electrode, it may further include a third electrical contact pad. The electrical interface may be configured to be in electrical communication with an evaluation meter. In some embodiments, the electrical interface is in electrical communication with an evaluation meter.

[0067] In some embodiments, the working electrode may include any material known to detect hydrogen peroxide. For example, the working electrode may include platinum, a metal organic framework (MOF), e.g., nickel based on adipic acid and piperazine; polyethyleneimine-Au nanoparticles zinc protoporphyrin;

[0068] In many embodiments, the intra-oral tip may include a nozzle jacket. The nozzle jacket may include a nozzle. The nozzle may be configured to deliver and/or extract a liquid sample from a site-specific location on a tooth surface. In several embodiments, the nozzle may protrude from the intra-oral tip at a distance of about 2 mm to about 20 mm. For example, the nozzle may protrude from the intra-oral tip at a distance in mm of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, or a value within a range between any of the preceding values, for example, between about 8 and about 12, between about 5 and about 15, or the like. In some embodiments, the nozzle may protrude about 10 mm. The protrusion would not only provide comfort to the subject but would also allow for better control in site-specific delivery of sugar compositions and/or withdraw of liquid samples described herein.

[0069] In some embodiments, the nozzle may have an outer diameter of less than about 2 mm.

[0070] In some embodiments, the nozzle may have an inner diameter of less than about 1 mm.

[0071] In many embodiments, the nozzle may be configured to deliver an amount of a sugar composition to a site-specific tooth surface location.

[0072] In some embodiments, the intra-oral tip may include notches to facilitate bending of the intra-oral tip into an inclined position. The intra-oral tip may be bent, with respect to a longitudinal axis A parallel to a planar elongated shaft, at an angle Q of about 1 to about 90 degrees. For example, the angle may be in degrees of about 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90, or a value between a range of any of the preceding values, for example, between about 10 and about 80, between about 20 and about 60, or the like. In other embodiments, the intra-oral tip aligns with a plane defined by longitudinal axis A and the elongated shaft, i.e., 0 = 0 degrees.

[0073] In some embodiments, an enzymatic matrix may be housed within the chamber such that the liquid sample may interact with the enzymatic matrix.

[0074] In many embodiments, the intra-oral tip may include a counter electrode and a working electrode in fluid communication with the chamber. The counter electrode and working electrode may be in communication with electrical interface via electrically conductive tracks and, respectively, that extend along the shaft.

[0075] In some embodiments, the intra-oral tip may further include a reference electrode. The reference electrode may be in communication with an electrical contact pad in the electrical interface via an electrically conductive track.

[0076] In many embodiments, the venting channel may overlay one or more of electrically conductive tracks and be in communication with the chamber. The venting channel may be configured to connect to a vacuum source near the second end. In some embodiments, the vacuum source is a vacuum. In other embodiments, the vacuum source is a reservoir filled with air. Upon pressing and releasing the air-filled reservoir, the expansion of the reservoir may afford a suctioning effect that allows for liquids, especially liquids with higher viscosities, to be withdrawn into the nozzle.

[0077] In many embodiments, the venting channel keeps the pressure during uptake in balance within the sensor. [0078] In some embodiments, the venting channel terminates at a vent opening outside of the oral cavity in order to avoid the closure of the venting opening by saliva, e.g., near the second end. In some embodiments, the venting channel terminates at a vent opening opposite the intra-oral tip along the elongated shaft.

[0079] In some embodiments, the vent opening may be near the electrical interface. In some embodiments, the venting channel does not contain a vent opening near the first end. In some embodiments, the venting channel does not contain vent opening along the sides of the venting channel.

[0080] In other embodiments, the lactate biosensor may include a reservoir filled with a sugar composition. The reservoir may be fitted to a delivery pipette to in order to administer the sugar composition via the nozzle. In some embodiments, the pipette may be adhered to the lactate biosensor.

[0081] In some embodiments, the lactate biosensor may include a reservoir having one or more compartments. Each compartment may independently be filled with air, a sugar composition, or a cleaning composition. Each compartment in the reservoir may be connected to a channel within a pipette extending to the nozzle. The reservoir may be fitted to one or more of a pipette and a venting channel.

[0082] In some embodiments, the lactate biosensor may further include a break strip. The break strip may serve as a removable handle. In some embodiments, the break strip is made from the same material as the lactate biosensor. In other embodiments, the break strip is made from a different material as the lactate biosensor. In some embodiments, the break strip is connected to the electrical interface. In some embodiments, lactate biosensor with a break strip may be considered a dental instrument.

[0083] In many embodiments, the lactate biosensor may be housed by a cover layer and a support layer.

[0084] In various embodiment, any lactate biosensor described herein may be used within any dental instrument described herein.

[0085] In various embodiments, any lactate biosensor described herein may be used in any method described herein.

[0086] In various embodiments, any lactate biosensor described herein may be used within any dental instrument described herein for use in any method described herein.

Enzymatic Matrix

[0087] In many embodiments, the enzymatic matrix may be housed within an enzymatic reservoir in fluid communication with the chamber. [0088] In some embodiments, the enzymatic matrix may include lactate oxidase. Lactate oxidase converts lactate and/or lactic acid into pyruvate and hydrogen peroxide in the presence of oxygen.

[0089] In many embodiments, hydrogen peroxide is measured by an evaluation meter via cyclic voltammetry. In some embodiments, a voltage (e.g., -0.5V to +1.0V) may be applied across the chamber and the reference electrode resulting in a current flow (e.g., ±5mA). The current peak values (oxidation and reduction) resulting from cyclic changes in voltage (e.g., -0.5V to -1 0V) may be used to calculate lactate/lactic acid concentration within a liquid sample.

[0090] In other embodiments, the enzymatic matrix may include any enzyme known to convert lactate/lactic acid to products detectable via electrochemical means.

[0091] In some embodiments, the enzymatic matrix may include lactate dehydrogenase.

Sugar composition

[0092] In many embodiments, the sugar composition may include a pentose or hexose sugar.

[0093] In some embodiments, the sugar composition may include a monosaccharide or a disaccharide.

[0094] In some embodiments, the sugar composition may include a sugar selected from glucose, galactose, fructose, sucrose, lactose, and maltose. In other embodiments, the sugar is sucrose.

[0095] In some embodiments, the sugar composition may include honey.

[0096] In some embodiments, the sugar composition may be an aqueous dispersion or suspension.

[0097] In some embodiments, the sugar composition may include thickeners. Sugar compositions including thickeners may include thickeners typically found in toothpastes. For example, the sugar composition may include hydroxylethyl cellulose, sodium polyphosphate, xanthum gum, or the like.

[0098] In several embodiments, the sugar composition has a viscosity that allows for application of the sugar composition to a tooth surface such that the surface tension is high enough to keep the sugar composition in the area applied. For example, the sugar composition may have a viscosity of about 500 cP to about 10,000 cP at a temperature of about 20 °C to about 25 °C. For example, the sugar composition has a viscosity in cP at a temperature of about 20 °C to about 25 °C of about 500; 1,000; 2,000; 3,000; 4,000; 5,000; 6,000; 7,000; 8,000; 9,000; or 10,000, or a value in a range between any of the preceding values, for example, between about 3,000 cP and about 8,000 cP, between about 5,000 cP and about 9,000 cP, or the like. [0099] In some embodiments, the sugar solution may include a dye. The dye may adhere to caries-causing areas or simply allow a user to visualize the area under testing.

Dental Instruments

[0100] In various embodiments, a dental instrument for use in detecting caries activity at a site- specific locale of a tooth surface is described. The dental instrument may include any lactate biosensor described herein and an evaluation meter. The lactate biosensor may include an elongated shaft having a first end and a second end opposite the first end; an intra-oral tip at the first end and having an inlet channel for receiving a liquid sample from the tooth surface; a chamber; an enzymatic matrix; a working electrode; a counter electrode; an electrical interface at the second end and electrically connected to the working electrode and the counter electrode; and a venting channel extending along at least a portion of the elongated shaft and terminating at the second end at a vent opening. The inlet channel, the enzymatic matrix, the working electrode, the counter electrode, and the venting channel may be in fluid communication with the chamber. The lactate biosensor may generate an electrical output based on an interaction between the liquid sample and the enzymatic matrix. The evaluation meter may be electrically connected to the lactate biosensor and may detect and transform the electrical output to provide a signal indicating a degree of caries activity.

[0101] In some embodiments, enzymatic activity within the lactate biosensor may produce an electrical output detected by the evaluation meter. The evaluation meter may convert the electrical output to a signal providing information about the degree of caries activity. For example, an electrical output determined to indicate a lactate concentration of greater than 3 mM may suggest the presence of caries activity at the tooth surface.

[0102] In some embodiments, the dental instrument may include a reservoir. The reservoir may include a sugar composition. The dental instrument may further include a means for dispensing the sugar composition to the tooth surface. For example, the means may include a dispensary channel such as a pipette, or a pipette equipped with a micro-brush.

[0103] The dental instruments of the present disclosure allow for a user to measure caries activity at a site-specific location on a tooth surface. Other methods for measuring caries-causing bacteria do not appear to be site -specific and can generally only provide information on the overall bacteria prevalence in the mouth.

[0104] In some embodiments, the dental instrument further includes a handle configured to accept the lactate biosensor in electrical connection. In some embodiments, the handle may house the evaluation meter. In some embodiments, the handle may be configured to allow for connecting of a venting channel to a vacuum. In some embodiments, the handle may include a vacuum. [0105] In many embodiments, the dental instrument may include a battery. The battery may be housed with the handle.

[0106] In some embodiments, the handle may include a receiving slot configured to electrically accept the lactate biosensor. The receiving slot may include a retention spring for securing the lactate biosensor within the receiving slot.

[0107] In some embodiments, the handle may include one or more status indicators. The status indicators may indicate the presence or absence of caries activity at or above a caries activity threshold. The status indicators may, for example, be LED lights. For example, a red light may indicate absence of caries activity or absence of caries activity above a caries activity threshold. For example, a green light may indicate presence of caries activity or presence of caries activity above a caries activity threshold.

[0108] In some embodiments, the handle may include an activation button. Compressing the activation button may one or more of turn on the device, expel gas (engage internal vacuum), expel a sugar composition, expel a cleaning composition, or a combination thereof.

[0109] In many embodiments, the dental instrument may include a display window. The dental instrument may include a display window on a handle. In some embodiments, the display window may be configured to indicate a color or alpha-numeric value representing the level of caries activity. The value indicating caries activity may be, for example, a numeric electrochemical value in millivolts (mV), to which a caries activity level is associated. When the evaluation meter transforms an electrical output from the lactate biosensor, a numeric value indicating caries activity in the form of an integer or percentage value may be displayed at the display window. The electrical output from an electrochemical signal (afforded by the interaction of the lactic acid and the enzymatic matrix) may undergo a mathematical transformation, wherein the transformation provides the value representing the caries activity level. For example, in some embodiments a numeric value between 1 and 10 may provide a simple representation of the caries activity level, wherein“1” may represent low or no caries activity and higher numbers up to 10 may represent a relatively higher level of caries activity. Alternatively, a percentage between 0% and 100% may provide a simple representation of the caries activity level, where, for example, “0% or lower percent values represents low or no caries activity and higher percentages, greater than 80%, greater than 90%, numbers up to 100%, represent a relatively higher level of caries activity. In other embodiments, the display window may display a color, for example, red, yellow, or green, indicating relative level of caries activity as high, mid-range, low, respectively. In other embodiments, the display window may display one or more words or alpha character abbreviations indicating relative level of caries activity, for example“Fow” or“Mid” or“High.” In some embodiments, for all the display value examples described above for the representation of the caries activity level a threshold value may be assigned, above which or below which certain treatment activities may be recommended.

Methods

[0110] In various embodiments, a method of detecting caries activity at a site-specific locale on a tooth surface is described. The method may include providing a dental instrument described herein. The method may include applying a sugar composition to the site-specific locale and allowing the sugar composition to interact with bacteria at the site-specific locale to form a liquid sample. The method may include withdrawing at least a portion of the liquid sample with at least a portion of the dental instrument and subjecting the liquid sample to a lactate measurement. The method may include determining a degree of caries activity according to a lactate measurement value.

[0111] In various embodiments, a method of detecting caries activity at a site-specific locale on a tooth surface is described. The method may include providing a lactate biosensor described herein. The method may include applying a sugar composition to the site-specific locale and allowing the sugar composition to interact with bacteria at the site-specific locale to form a liquid sample. The method may include withdrawing at least a portion of the liquid sample with the lactate biosensor and subjecting the liquid sample to a lactate measurement. The method may include determining a degree of caries activity according to a lactate measurement value.

[0112] In many embodiments, the method may further include removing a break strip from a lactate biosensor prior to subjecting the liquid sample to a lactate measurement.

[0113] In many embodiments, the method may further include inserting the lactate biosensor into an evaluation device for the subjecting of the liquid sample to the lactate measurement.

[0114] In various embodiments, a method of detecting caries activity on a tooth surface is described. The method may include providing a dental instrument or lactate biosensor described herein. The method may include withdrawing saliva from a site-specific tooth surface location and applying a sugar composition to the saliva. The method may include allowing the sugar composition to interact with bacteria in the saliva to form a liquid sample. The method may include subjected the liquid sample to a lactate measurement and determining a degree of caries activity according to a lactate measurement value.

[0115] In various embodiments, a method of detecting caries activity on a tooth surface is described. The method may include providing a dental instrument or lactate biosensor described herein. The method may include withdrawing saliva from a tooth surface and applying a sugar composition to the saliva. The method may include allowing the sugar composition to interact with bacteria in the saliva to form a liquid sample. The method may include subjected the liquid sample to a lactate measurement and determining a degree of caries activity according to a lactate measurement value.

[0116] In some embodiments, the withdrawing of saliva may be done with the dental instrument or lactate biosensor.

[0117] In some embodiments, the applying of the sugar composition to the saliva may occur within the chamber of the lactate biosensor. In other embodiments, the applying of the sugar composition to the saliva occurs in a container.

[0118] In many embodiments, the applying of the sugar composition at a site-specific locale of the methods described herein, may be accomplished with certain lactate biosensors having certain features described herein, e.g., nozzle jacket configured to precisely dispense sugar compositions.

[0119] In many embodiments, the methods described herein may further include allowing the sugar composition to interact with the bacteria for a period of between about 0.01 minutes to about 5 minutes. The sugar composition may be allowed to interact with the bacteria for a period in minutes of about 0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6. 0.7. 0.8, 0.9, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.5, 4.0, 4.5, and 5.0, or a value within a range between any of the preceding values, for example, between about 0.2 and about 0.6, between about 0.5 and about 2.0, or the like. In some embodiments, the sugar composition may be allowed to interact with the bacteria for about 1 minute to about 2 minutes.

[0120] In many embodiments, the methods described herein may further include comparing the lactate measurement value to a reference value, wherein the reference value indicates a lactic acid/lactate concentration at a caries activity threshold.

[0121] In many embodiments, the lactate measurements of the methods described herein may include inserting the lactate biosensor into an evaluation meter.

[0122] In several embodiments, the methods described herein may further include formulating a treatment plan based on the lactate measurement value. In some embodiments, the treatment plan may include placing the tooth surface location having caries activity on clinical treatment plan watch. The tooth surface may be evaluated again after a period, e.g., 3, 6, 9, or 12 months. Further evaluation of a watched tooth surface location may show increased or decreased lactic acid production. Surfaces showing increased lactic acid production may require treatment, e.g., remineralization treatments, dental restorations, or the like.

[0123] In several embodiments, the methods described herein may further include formulating a treatment plan based on the lactate measurement value. In some embodiments, the treatment plan may include remineralization treatments for a tooth surface location having a caries activity value below a predetermined threshold value. The tooth surface location may be evaluated after a period post-treatment, e.g., 3, 6, 9, or 12 months. Further evaluation of a treated tooth surface may show increased or decreased lactic acid production. Surfaces showing increased lactic acid production may require further treatment, e.g., remineralization treatments, dental restorations, or the like.

[0124] In several embodiments, the methods described herein may further include formulating a treatment plan based on the lactate measurement value. In some embodiments, the treatment plan may include dental restoration for a tooth surface location having a caries activity value above a predetermined threshold value. The tooth surface may be evaluated after a period post-treatment, e.g., 3, 6, 9, or 12 months. Further evaluation of a treated tooth surface may show increased or decreased lactic acid production. Surfaces showing increased lactic acid production may require further treatment, e.g., remineralization treatments, dental restorations, or the like.

Kits

[0125] In various embodiments, a kit is described. The kit may include a dental instrument described herein, a sugar composition described herein, and a set of instructions directing a user to carry out a method described herein.

[0126] In various embodiments, a kit is described. The kit may include a lactate biosensor described herein, a sugar composition described herein, and a set of instructions directing a user to carry out a method described herein.

[0127] In some embodiments, the kit may further include an evaluation meter.

[0128] In some embodiments, the instructions may further direct a user to remove a break strip from the lactate biosensor prior subjecting the liquid sample to a lactate measurement.

[0129] In some embodiments, the kits described herein may further include a cleaning composition.

Claims

CLAIMS What is claimed is:

1. A dental instrument for use in detecting caries activity at a site-specific locale of a tooth surface, the dental instrument comprising:

a lactate biosensor, the lactate biosensor comprising:

an elongated shaft comprising a first end and a second end opposite the first end, an intra-oral tip at the first end and comprising an inlet channel for receiving a liquid sample from the tooth surface,

a chamber,

an enzymatic matrix,

a working electrode,

a counter electrode,

an electrical interface at the second end and electrically connected to the working electrode and the counter electrode,

a venting channel extending along at least a portion of the elongated shaft and terminating at the second end at a vent opening,

wherein the inlet channel, the enzymatic matrix, the working electrode, the counter electrode, and the venting channel are in fluid communication with the chamber, and

wherein the lactate biosensor generates an electrical output based on an interaction between the liquid sample and the enzymatic matrix; and an evaluation meter,

wherein the evaluation meter is electrically connected to the lactate biosensor, and wherein the evaluation meter detects and transforms the electrical output to provide signal indicating a degree of caries activity.

2. The dental instrument of claim 1, wherein the intra-oral tip is inclined at an angle of about 1 to about 90 degrees with respect to a longitudinal axis parallel to the elongated shaft.

3. The dental instrument of any one of the preceding claims, the lactate biosensor further comprising a reference electrode.

4. The dental instrument of any one of the preceding claims, further comprising a vacuum supply.

5. The dental instrument of claim 4, wherein the vacuum supply is configured to connect to the venting channel at the vent opening.

6. The dental instrument of any one of claims 4-5, wherein the vacuum supply is a reservoir filled with gas.

7. The dental instrument of any one of the preceding claims, further comprising a reservoir comprising a sugar composition and a means for dispensing the sugar composition to the tooth surface.

8. The dental instrument of any one of the preceding claims, further comprising a handle configured to accept the lactate biosensor in electrical connection, wherein the handle houses the evaluation meter.

9. The dental instrument of any one of the preceding claims, wherein the evaluation meter transforms the electrical output received and to a signal indicating the degree of caries activity by one or more of a display window or LED indicator.

10. A lactate biosensor for use in detecting caries activity at a site-specific locale of a tooth surface, the lactate biosensor being described in any one of claims 1-7.

11. The lactate biosensor of claim 10, further comprising a break strip.

12. A method of detecting caries activity at a site-specific locale on a tooth surface, the method comprising:

providing a dental instrument of any one of claims 1-9;

applying a sugar composition to the site-specific locale;

allowing the sugar composition to interact with bacteria at the site-specific locale to form a liquid sample;

withdrawing at least a portion of the liquid sample with at least a portion of the dental instrument;

subjecting the liquid sample to a lactate measurement; and

determining a degree of caries activity according to a lactate measurement value.

13. The method of claim 12, further comprising comparing the lactate measurement value to a reference value, wherein the reference value indicates a lactate concentration at a caries activity threshold.

14. A kit comprising a dental instrument of any of one of claims 1-9, a sugar composition, and a set of instructions directing a user perform a method of any one of claims 12-13.

15. A kit comprising a lactate biosensor of any of one of the claims 10-11, a sugar composition, and a set of instructions directing a user to:

apply the sugar composition to a site-specific locale;

allow the sugar composition to interact with bacteria at the site-specific locale to form a liquid sample;

withdraw at least a portion of the liquid sample;

subject the liquid sample to a lactate measurement; and

determine a degree of caries activity according to a lactate measurement value.