Intra-oral devices and methods for making and using them

Abstract

A device is disclosed that includes a device body configured to couple to dentition. The device may include a sensor configured to couple to the device body to be positioned to be adjacent to tissue when the device body couples to the dentition.

Description

INTRA-ORAL DEVICES AND METHODS FOR MAKING AND USING THEMCROSS-REFERENCE TO RELATED APPLICATIONSThis application claims benefit of priority from United States Provisional Patent Application 63 / 666,065, filed on June 28, 2024, the disclosure of which is incorporated herein by reference.TECHNICAL FIELD

[0001] This invention generally relates to devices to be placed inter-orally and related methods for making and using.BACKGROUND

[0002] Dental devices such as orthodontic devices and mandibular advancement devices (MAD) have a long residence inside a patient’s mouth. For example, for a MAD, the intra-oral dwell time is throughout the time the patient is asleep. During this time, many physiological and physical changes occur in the patient’s body that affect the efficacy of the MAD and the patient’s health.SUMMARY

[0003] This Summary is provided to introduce a selection of concepts in simplified form that can be further described below in the Detailed Description. This Summary is not intended to identify key aspects or essential aspects of the claimed subject matter. All features of exemplary embodiments which can be described in this disclosure and can be not mutually exclusive can be combined with one another. Elements of one embodiment can be utilized in the other embodiments without further mention. Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments in conjunction with any accompanying Figures.

[0004] In some aspects, the techniques described herein relate to a device including: a device body configured to couple to dentition; and a sensor device configured to couple to the device body, the sensor device including a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.

[0005] In some aspects, the techniques described herein relate to a device, wherein the protruding portion is to press the tissue when the device body couples to the dentition.

[0006] In some aspects, the techniques described herein relate to a device, wherein the protruding portion includes the sensor.

[0007] In some aspects, the techniques described herein relate to a device, wherein the tissue includes buccal mucosa. In some aspects, the techniques described herein relate to a device, wherein the tissue includes a region of oral mucosa closer to a maxillary arch than to a lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes oral mucosa around a lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes buccal mucosa around a cheek.

[0008] In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, further including a receiving device configured to be operably linked to or connected to the sensor to receive the obtained information. In some aspects, the techniques described herein relate to a device, wherein the receiving device is disposed outside the oral cavity.

[0009] In some aspects, the techniques described herein relate to a device, wherein the sensor device is configured to contact the tissue. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a plurality of pivots. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a plurality of bend points.

[0010] In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding in a first direction substantially away from a surface of the sensor device.

[0011] In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding from a surface of the sensor by about 0.1 mm to about 10 mm.

[0012] The details of one or more exemplary embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.

[0013] All publications, patents, patent applications, cited herein are hereby expressly incorporated by reference in their entireties for all purposes.DESCRIPTION OF DRAWINGS

[0014] It is to be expressly understood that the drawings set forth herein are illustrative of exemplary embodiments provided herein and are not meant to limit the scope of the invention as encompassed by the claims.

[0015] FIG. 1 illustrates an example soft and hard tissues in an oral cavity in some embodiments.

[0016] FIG. 2 illustrates a sensor device with three different bend points in some embodiments.

[0017] FIG. 3 illustrates a flexible circuit board configurations for an arch form with changed radiuses to allow insertion of a flexible sensor circuit board as a sensor device in some embodiments.

[0018] FIG. 4 illustrates a protruding portion protruding with respect to a surface of a sensor device in some embodiments.

[0019] FIG. 5 illustrates an orthodontic device with a sensor pocket and a circuit channel design in some embodiments.DETAILED DESCRIPTION

[0020] Intra-oral devices such as dental devices, orthodontic devices and mandibular advancement devices (MAD) have a long residence inside a patient’s mouth. For example, for a MAD, the intra-oral dwell time is throughout the time the patient is asleep. During this time, many physiological and physical changes occur in the patient’s body that affect the efficacy of the MAD and the patient’s health.

[0021] In some aspects, the techniques described herein relate to an oral device including: a device body configured to couple to dentition; and a sensor device configured to couple to the device body, the sensor device including a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.

[0022] In some aspects, the techniques described herein relate to a device including: a device body configured to couple to dentition; and a sensor device configured to couple to the device body, the sensor device including a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.

[0023] In some aspects, the techniques described herein relate to a device including: a device body configured to couple to dentition; and a sensor device configured to couple to the device body, the sensor device including a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be protruded in an oral cavity when the device body couples to the dentition.

[0024] In some aspects, the techniques described herein relate to a device, wherein the protruding portion is to contact the tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is to press the tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is to push the tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is to press the tissue within the oral cavity when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is to push the tissue within the oral cavity when the device body couples to the dentition.

[0025] In some aspects, the techniques described herein relate to a device, wherein the protruding portion includes the sensor.

[0026] In some aspects, the techniques described herein relate to a device, wherein the tissue includes soft tissue. In some aspects, the techniques described herein relate to a device, wherein the tissue includes oral mucosa. In some aspects, the techniques described herein relate to a device, wherein the tissue includes buccal mucosa. In some aspects, the techniques described herein relate to a device, wherein the tissue includes a region of buccal mucosa closer to a maxillary arch than to a lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes a region of buccal mucosa closer to a mandibular arch than to a lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes gingiva. In some aspects, the techniques described herein relate to a device, whereinthe tissue includes palate. In some aspects, the techniques described herein relate to a device, wherein the tissue includes a lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes an oral mucosa around a upper lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes an oral mucosa around a lower lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes an oral mucosa above a upper lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes an oral mucosa below a lower lip.

[0027] In some aspects, the techniques described herein relate to a device, wherein the tissue includes a region of oral mucosa closer to a maxillary arch than to a lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes a region of oral mucosa closer to a mandibular arch than to a lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes a tongue. In some aspects, the techniques described herein relate to a device, wherein the tissue includes a tooth. In some aspects, the techniques described herein relate to a device, wherein the tissue includes retromolar trigone. In some aspects, the techniques described herein relate to a device, wherein the tissue includes tonsil. In some aspects, the techniques described herein relate to a device, wherein the tissue includes uvla. In some aspects, the techniques described herein relate to a device, wherein the tissue includes a floor of mouth. In some aspects, the techniques described herein relate to a device, wherein the tissue includes buccal mucosa around a lip. In some aspects, the techniques described herein relate to a device, wherein the tissue includes buccal mucosa around a cheek.

[0028] In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, further including a receiving device configured to be operably linked to or connected to the sensor to receive the obtained information. In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to detect a signal from the adjacent tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, further including a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the signal. In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to sense a parameter from the adjacent tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, further including a receiving deviceconfigured to be operably linked to or connected to the sensor to receive information associated with the parameter. In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to sense a condition of the adjacent tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, further including a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the condition. In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to sense a condition of the adjacent tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, further including a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the condition. In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to sense a physiological condition of the adjacent tissue when the device body couples to the dentition. In some aspects, the techniques described herein relate to a device, further including a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the physiological condition.

[0029] In some aspects, the techniques described herein relate to a device, 35, 37, 39, 41, 43, wherein the receiving device is disposed outside the oral cavity. In some aspects, the techniques described herein relate to a device, 35, 37, 39, 41, 43, wherein the receiving device is disposed outside the oral cavity. In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to be coupled to the device to sense through an outer surface of the device. In some aspects, the techniques described herein relate to a device, wherein the sensor device is configured to contact the tissue. In some aspects, the techniques described herein relate to a device, wherein the sensor is configured to be positioned to be close to the tissue. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a flexible portion. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a flexible portion to be deformed.

[0030] In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a flexible portion to be deformed when the device couples to the dentition. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a flexible portion to be deformed when the sensor device contacts the dentition. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes an inflexible portion. In some aspects, the techniques described hereinrelate to a device, wherein the sensor device includes a pivot. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a plurality of flexible portions. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes at least three flexible portions. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a plurality of inflexible portions. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a plurality of pivots. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes at least three pivots. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a bend point. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes a plurality of bend points. In some aspects, the techniques described herein relate to a device, wherein the sensor device includes at least three bend points.

[0031] In some aspects, the techniques described herein relate to a device, wherein the sensor device is bendable to be inserted into the device. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding in a first direction substantially away from a surface of the sensor device. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding in a second direction substantially parallel to a surface of the sensor device. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding in a second direction different from the first direction. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding in a second direction substantially parallel to the surface of the sensor device.

[0032] In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding from a surface of the sensor by about 0.1 mm to about 10 mm. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 7 mm. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 5 mm. In some aspects, the techniques described herein relate to a device, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 4 mm.

[0033] In some aspects, the techniques described herein relate to a device, wherein the device includes a recess or a protrusion on a surface of the device, and wherein the sensor device is configured to be coupled to the recess or the protrusion.

[0034] In some aspects, the techniques described herein relate to a device, wherein the recess include the protrusion to push the sensor device against the tissue. In some aspects, the techniques described herein relate to a device, wherein the recess or the protrusion includes a slot, a groove, or an insert, and wherein the sensor device is configured to be coupled to the slot, the groove, or the insert. In some aspects, the techniques described herein relate to a device, wherein the device includes a curved surface. In some aspects, the techniques described herein relate to a device, wherein the curved surface of the device corresponds to a curve of a dental arch in the oral cavity.

[0035] In some aspects, the techniques described herein relate to a device, wherein the sensor device includes data storage operably linked to or connected to the sensor.

[0036] In some aspects, the techniques described herein relate to a device, wherein the data storage is built into a Radio Frequency Identity (RFID) chip or Near-Field Communication (NFC) chip.

[0037] In some aspects, the techniques described herein relate to a device, wherein a maximum distance between a surface of the sensor facing toward the tissue and an outer surface of the device is from about 0.01 mm to about 5 mm.

[0038] In some aspects, the techniques described herein relate to a device, wherein the sensor is a photoplethysmography (PPG) sensor, a physiological sensor, a physical sensor, a chemical sensor, a proximity sensor, a vibration sensor, or a positional sensor. In some aspects, the techniques described herein relate to a device, wherein the sensor includes a silicone, plastic, a liquid crystal polymer (LCP) substrate, an LCP base material adhered to a cladding, a fiber or a yarn, paper (optionally including cellulose nanofibers (CNFs), a polyaniline nanofiber / graphite nanofiber (PANI / GNF) nanocomposite, or a polyaniline (PANI) supportive matrix, or a combination thereof.

[0039] In some aspects, the techniques described herein relate to a device, wherein the device is a mandibular advancement device (MAD), or an orthodontic device, or a device that repositions a mandible or a maxilla.

[0040] In some aspects, the techniques described herein relate to a method including coupling an oral device to dentition, wherein the device includes: a device body configured to couple to the dentition; and a sensor device configured to couple to the device body, the sensor device including a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.

[0041] In some aspects, the techniques described herein relate to a method including coupling a device to dentition, wherein the device includes: a device body configured to couple to the dentition; and a sensor device configured to couple to the device body, the sensor device including a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.

[0042] In some aspects, the techniques described herein relate to a method including coupling a device to dentition, wherein the device includes: a device body configured to couple to the dentition; and a sensor device configured to couple to the device body, the sensor device including a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be protruded in an oral cavity when the device body couples to the dentition.

[0043] The present disclosure relates to a device, wherein the data storage is built into a Radio Frequency Identity (RFID) chip or Near-Field Communication (NFC) chip.

[0044] The present disclosure relates to a device, wherein a maximum distance between a surface of the sensor facing toward the tissue and an outer surface of the device is from about 0.01 mm to about 5 mm.

[0045] The present disclosure relates to a device, wherein the sensor is a photoplethysmography (PPG) sensor, a physiological sensor, a physical sensor, a chemical sensor, a proximity sensor, a vibration sensor, or a positional sensor.

[0046] The present disclosure relates to a device, wherein the sensor includes a silicone, plastic, a liquid crystal polymer (LCP) substrate, an LCP base material adhered to a cladding, a fiber or a yarn, paper (optionally including cellulose nanofibers (CNFs), a polyanilinenanofiber / graphite nanofiber (PANI / GNF) nanocomposite, or a polyaniline (PANI) supportive matrix, or a combination thereof.

[0047] The present disclosure relates to a device, wherein the device is a mandibular advancement device (MAD), or an orthodontic device, or a device that repositions a mandible or a maxilla.

[0048] In some embodiments, it can be useful to allow the MAD to respond in real time to the changes in the patient in order to provide the most effective mandibular position adjustment for the patient at the particular time. In addition, physicians may benefit from knowing both real time changes in the patient’s body and the history of these changes while the dental device, for example, a MAD, is being used in order to provide a better treatment regimen or react to a real time medical issue. Accordingly, means to accurately measure body physiological and physical changes by the dental devices are provided.

[0049] Mandibular advancement devices (MAD) have a long residence inside a patient's mouth, namely throughout the time the patient is asleep. During this time, many physiological and physical changes occur in the patient's body that affect the efficacy of the MAD and the patient's health. It is useful to allow the MAD to respond in real time to the changes in the patient in order to provide the most effective mandibular position adjustment for the patient at the particular time. In addition, physicians would like to know the history of the changes in the patient's body while the MAD is being used in order to provide a better treatment regimen.

[0050] In some embodiments, during the design of the MAD having at least one sensor, the sensor and the pocket into which it is placed are design library elements in computer aided design (CAD) program. The designer chooses the relevant library element and the location where the sensor should be placed on the MAD and the CAD program provides a design accordingly. For a discussion of designing MADs using library elements, see the aboveincorporated publication 2018 / 0024530.

[0051] The sensors can be in wireless communication with a base, transmitting the data they obtained. Various modes of wireless communication are well-known in the art. Currently, the most popular mode appears to be Bluetooth® communication. Other modes such as radio, infrared, magnetic, or the like can also be used. All modes of wireless communication now known or developed in the future are contemplated for use with the presently disclosed sensors.

[0052] In some embodiments, the base is software contained in a physical cradle. The cradle is configured for wireless communication with the sensor embedded in the MAD. In some embodiments, following the use, the patient places the MAD in the cradle, which can optionally recharge the batteries of the sensor. In some embodiments, the cradle is configured to clean the MAD, for example, by providing a bath into which the MAD can be placed, or by having a well-contained chamber for the MAD to be cleaned using cleansers or steam or the like. In other embodiments, the base is a software (including an app) on a smart phone (e.g., iPhone®, Galaxy®), smart tablet (e.g., iPad®, Surface®), or a laptop or desktop computer (collectively “a device”).

[0053] In some of the embodiments, the base logs the position of the mandible in time. The HCP can then correlate the physiological response at a certain time point with the mandibular position at that time point and make treatment decisions accordingly.

[0054] In some embodiments, the base and the MAD operate in a feedback system. When the data obtained by the sensor is communicated with the base, the base analyzes the data and, based on a pre-scripted routine, relays a command to the MAD to take an action in response. In some embodiments, the pre-scripted routine is based on a prescription by the HCP.

[0055] In some embodiments, the response is a mechanical response. In these embodiments, the MAD comprises a stepper motor, for example embedded as dorsal style, which can cause the mandible to advance or retract either symmetrically or asymmetrically, by 0.1 mm, or any other multiple thereof.

[0056] In some embodiments, the base will sound an alarm audible enough to wake the patient up, if the physiological data, such as the blood oxygen level or air flow disturbance, indicate an unhealthy state for the patient to continue to be sleeping. In other embodiments, the base relays a command to the MAD to release a repugnant chemical substance in the mouth, such as one with a bitter taste, to wake the patient up.

[0057] In some embodiments, the base is programmed to alert the emergency medical services if the physiological data is worsening and the patient shows no sign of waking up, for example, by turning the alarm off.

[0058] In some embodiments, the presently disclosed combination of MAD and sensors is used to deliver medications to the patient in a controlled fashion. In some of theseembodiments, the MAD comprises built-in refillable cavities that can be filled with prescribed medication. In other embodiments, the MAD comprises a location for a prefilled container of medication to be placed. In any case, the design of the MAD with the medication-dispensing components is such that the patient does not feel the bulk of the medication-dispensing components and the MAD is as comfortable to wear as if it did not have the medicationdispensing components.

[0059] In response to a time cue or input from an embedded sensor, the base relays a command to the MAD and the medication-dispensing components to release a preset amount of the medication either between the cheek and the gum for a buccal administration or into the patient's mouth for the medication to be inhaled. Examples include stress reducing agents, calming agents, glucose, insulin, nitroglycerin or other heart medications for atrial fibrillation or unstable angina, and the like.

[0060] In some embodiments, such as those where the MAD is as described in the aboveincorporated International Patent Application No. PCT / US2019 / 029471, the MAD comprises an internal mechanism to advance the mandible forward, for example by turning a screw. In some of these embodiments, a small stepper motor is connected with the advancement mechanism. In some embodiments, in response to data obtained from the sensors, for example with respect to snoring, whether the flow of air through the mouth is laminar or turbulent, heart rate variability, blood oxygen saturation levels, and the like, the base sends a command to the MAD stepper motors to advance or retract the mandible by a small increment until the situation is rectified, for example the air flow becomes laminar, or snoring subsides, or blood oxygen levels rise. The biofeedback provided by the sensors allow the base to control the treatment in real time.

[0061] In some embodiments, the base is also in wireless communication with software on a device operated by a health care provider (HCP). In these embodiments, the base communicates the collected data directly to the HCP device, where the HCP can monitor the progress of the patient without the need for the patient to make office visits. This feature is quite useful for individuals who travel constantly, such as salespersons, long distance drivers, airline pilots, and the like. By taking advantage of this feature, the HCP can continually monitor the patient and intervene with a recommendation if that is in the best interest of the patient. This way, problems are detected and corrected as they happen.

[0062] In some embodiments, the base communicates with the HCP software through the internet, phone lines, satellite, radio, microwave, or other forms of long distance communication now known or later developed.

[0063] In some embodiments, the base can analyze the data and, in accordance with a prescripted routine, cause the MAD to change the position of the mandible with respect to maxilla to maximize the efficacious result during the use of the MAD.

[0064] In some embodiments, multiple sensors are connected to the same sensing block, whereas in other embodiments, each sensor has its own sensing block.

[0065] To adjust the MAD to advance the mandible when such advancement is required, MADs currently on the market require the patient to turn a screw a number of times for the proper adjustment. When the screw is turned, a mobile unit of the MAD moves with respect to a stationary unit thereof. In many instances, each adjustment requires the screw to be turned more than twice. Patient compliance with this directive is not always 100% as some patients become distracted and forget how many times they turned the screw, or the screw is not turned all the way, and other similar problems.

[0066] In some embodiments, the MAD comprises barcodes that can be read by a barcode reader, such as a smart phone. QR codes, standard barcodes, and other similar readable figures can be used for the present purpose. A portion of the barcode is printed on the mobile unit and the rest of the barcode is printed on the stationary unit. At each unit increments, such as 0.1 mm, the two halves of the barcode align to create a code that corresponds to the position of the mobile unit with respect to the stationary unit. When the device has not been properly adjusted, the resulting barcode is a garble and does not result in any information being received. When the device is properly adjusted, the alignment of two halves of the barcode correspond to the code for the position of the device.

[0067] In some embodiments, provided are products of manufacture, also referred to herein as intra-oral or dental devices, that have flexible sensors that are configured to follow the contours of a patient’s hard or soft tissue. For example, FIG. 1 illustrates example soft and hard tissues in an oral cavity in some embodiments. In some embodiments, vital sign monitoring in intraoral space can be performed in the oral cavity, e.g., for less melanin difference in intraoral space, improving any skin reflectant vital sign monitoring system including PPG.

[0068] In some embodiments, an intra-oral device is provided, which may include a device body including an engagement member to engage a dentition of a patient, a sensor coupled to the device body to be positioned to be adjacent to soft tissue or hard tissue in an oral cavity of the patient when the intra-oral device is positioned or placed in the oral cavity of the patient, and a control device operably linked to or connected to the sensor.

[0069] In some embodiments, provided are manufactured products, intra-oral or dental devices, which can feature an inflexible, flat, or non-curved sensor situated on a curved surface of the intra-oral device or within a slot, groove, or inset on its surface. Optionally, the curvature of the intra-oral device 's surface closely mirrors that of a dental arch.

[0070] In some embodiments, manufactured products, intra-oral or dental devices, such as orthodontic devices and mandibular advancement devices (MADs), incorporate flexible sensors positioned on the device's surface to closely conform to the curved contour of a patient’s hard or soft tissues. This close contact enables the flexible sensor to provide more accurate readings of the patient’s physiological state.

[0071] In some embodiments, photoplethysmography (PPG) sensors may be employed in manufactured products, intra-oral or dental devices, as described herein, to measure volumetric variations in blood circulation. Since PPG sensors utilize optical measurements to monitor blood circulation and heart rate, having the PPG sensor conform to the contour of a patient’s soft tissues enhances the accuracy of the measurements.

[0072] In some embodiments, utilizing a PPG mounted on a flexible sensor can enable the precise measurement of physiological data.

[0073] Disclosed herein are sensors that, when combined with a mandibular advancement device (MAD), can measure certain biological or biophysical aspects about a patient.

[0074] One MAD contemplated to be used in combination with the presently disclosed sensors has been previously described. See, for example, U.S. Pat. Nos. 9,820,882, 9,808,327, US Patent Application Publications, 2018 / 0024530 and 2019 / 0105191, International Publication WO 2019 / 018309 Al, and International Patent Application No. PCT / US2019 / 029471. The disclosure of all the publications enumerated in this paragraph (“the above-incorporated publications”) are hereby incorporated by reference herein, including anydrawings, in particular such aspects of the disclosure that disclose an MAD, a method of design thereof, a method of manufacture thereof, or an accessory therefor.

[0075] Advantages of the MAD-sensor combinations disclosed herein are many. The device in its totality is 100% self-contained and resides completely secure inside the patient's mouth, enabling complete lip seal. The device is custom manufactured — by combining the patient's anatomical data input and a health care provider's (HCP) prescription with a manufacturing library of elements — to seamlessly integrate the sensors and device mechanisms with the patient's comfort in mind.

[0076] In some embodiments, the HCP's prescription includes the starting bite position, and optionally one or more of custom treatment features, such as anterior discluder, splint options, titration mechanism, and other features enumerated in the above-incorporated publications.

[0077] In some embodiments, if the MAD comprises more than one sensor, then the MAD is designed and manufactured such that the sensors are on one splint, either the upper or the lower splint, of the MAD. In other embodiments, the sensors are on different splints. Throughout the present disclosure, the splint bearing the sensor(s) is called the “technical splint,” while the splint without any sensors is called the “free splint.”

[0078] In some embodiments, the splints are designed such that the most critical components, e.g., the sensors, are protected. If there is to be a device failure due to, for example, the patient bruxing, chewing, or biting against the device, the free splint is designed to fail first before the technical splint. This is achieved by either making the free splint thinner than the technical splint, or by making the two splints from different materials. The free splint is easily remade at a lower cost and more expedient than the technical splint.

[0079] A variety of sensors are contemplated to be used with the disclosed MADs. In general, the sensors can be divided into the following categories: physiological sensors, physical sensors, chemical sensors, and positional sensors.

[0080] In some embodiments, physiological sensors measure and relay such physiological data as body temperature, respiration rate, heart rate, or other relevant physiological data, and / or any variability in the above values.

[0081] In some embodiments, physical sensors are those that detect the mode of breathing, e.g., vibration in the breathing, airflow rate, oxygen concentration of inhaled air, etc., and correlate that to airflow restriction. In some embodiments, the sensor is selected from an oxygen sensor measuring the oxygen concentration of the inhaled air, a carbon dioxide sensor measuring the carbon dioxide concentration of the exhaled air, a pressure sensor measuring the atmospheric pressure or the air pressure inside the oral cavity, an airflow sensor, a noise detector, or an actigraphy sensor. The sensors can also detect snoring, and / or perform airway flow signature analysis. In some embodiments, the sensor measures the pressure exerted on the MAD by the patient's teeth in order to measure the extent of clenching and / or grinding of dentition surfaces.

[0082] In some embodiments, chemical sensors are used to measure the body's physiological response to breathing. For example, the saliva pH, saliva sugar concentration, saliva conductivity, levels of stress markers, such as salivary cortisol, blood oxygen saturation level, blood pH, blood glucose levels, blood insulin levels, inflammatory markers, and the like, can be measured in real time and reported to the HCP via the base. Bacterial biosensors can provide information to the HCP on the level of bacterial activity in the mouth during sleep.

[0083] In some embodiments, positional sensors are used to record the position of the MAD in the mouth with respect to a predetermined reference location. The sensors can optionally track the movement of the mandible in the anterior-posterior, vertical, and / or lateral directions.

[0084] In some embodiments, the sensor is a component of a sensing block, which includes other components besides the sensor. In certain embodiments, the sensing block components include one or more of a battery (rechargeable or replaceable), a battery recharging circuit compatible with industry standards, if applicable, on-board memory, communication module, analog / digital converter to convert sensor voltage inputs to digital signal, a control module for activating stepper motors, and an I / O bus to connect to external sensors and motors.

[0085] In some embodiments, the sensor includes a light-based optical sensor configured to measure blood glucose levels using near-infrared (NIR), mid-infrared (MIR), or Raman spectroscopy principles. In such embodiments, the sensor is positioned to be in optical communication with highly vascularized oral tissue, such as the buccal mucosa or sublingual area, to enable non-invasive detection of blood glucose concentrations.

[0086] In some embodiments, sensing may involve mechanical sensing. For example, piezoresistive sensors may involve detecting changes in pressure or strain by measuring variations in electrical resistance, often used for monitoring pulse or respiration. For example, capacitive sensors may involve measure changes in capacitance due to mechanical deformation, which is useful for monitoring pulse rate, muscle movement, or arterial stiffness. For example, piezoelectric sensors may involve converting mechanical stress (like pressure or vibration) into electrical signals, commonly used for pulse and arterial stiffness measurements. For example, mechanoreceptors (biological) may involve natural receptors such as meissner’s and pacinian corpuscles in the skin detect touch, pressure, and vibration, sending signals to the nervous system.

[0087] In some embodiments, sensing may involve thermal sensing. For example, thermoresistive sensors may involve detecting temperature changes by measuring resistance changes in materials like metals or conductive polymers. For example, thermocouples may involve generating voltage in response to temperature gradients, used for body temperature monitoring. For example, thermoreceptors (biological) may involve free nerve endings and specialized structures (Krause’s end bulbs) in the skin sense temperature changes.

[0088] In some embodiments, sensing may involve electrical sensing. For example, electrodes may involve measuring electrical potentials from muscles (EMG), heart (ECG), or brain (EEG) through the skin, using conductive materials like carbon, silver, or goldl2. For example, neural electrical sensors may involve detecting voltage signals from nerve or muscle activity for monitoring or prosthetic control 1.

[0089] In some embodiments, sensing may involve optical sensing. For example, photoelectric sensors may involve use light (e.g., LEDs and photodetectors) to measure blood flow (photoplethysmography, ppg) or oxygen saturation (SPO2) through the skinl. For example, optoelectronic sensors may involve organic or flexible optoelectronic devices to detect pulse or oxygen levels by shining light into the skin and measuring reflected or transmitted light.

[0090] In some embodiments, sensing may involve electrochemical sensing. For example, electrochemical sensors may involve detecting chemical concentrations (e.g., glucose, lactate, electrolytes) in sweat or interstitial fluid through the skinl . For example, wearable patches mayinvolve using enzymatic or non-enzymatic reactions to convert chemical signals into electrical signals for monitoring.

[0091] In some embodiments, sensing may involve mucosa-based physiological sensing. For example, in some embodiments, sensing may involve chemical sensing. For example, chemosensors may detect chemical stimuli such as acids, co2, bile acids, and nutrients in mucosal tissues (e.g., duodenal mucosa)4. For example, g-protein-coupled receptors (GPCRS) may involve respond to specific molecules (e.g., glutamate, calcium, fatty acids) and trigger physiological responses such as secretion, digestion, or mucosal defense4. For example, acid sensors and ion transporters may involve detecting pH changes and regulating mucosal defense mechanisms. In some embodiments, sensing may involve mechanical sensing. For example, mechanoreceptors may involve present in mucosal tissues (though less studied than in skin), detect pressure, stretch, or movement, contributing to reflexes and feedback for digestion and absorptions. For example, In some embodiments, sensing may involve other technologies. For example, wireless miniature sensors may be delivered to mucosal surfaces (e.g., in the gastrointestinal tract) to sense properties like mucus viscosity or chemical composition, often using magnetic actuation or soft robotics for minimally invasive placement.

[0092] In some embodiments, Prototype of a sensor-integrated intraoral mouthguard with an embedded flexible circuit board for salivary biomarker monitoring, where such devices incorporate multiple sensors into a mandibular advancement appliance to collect physiological, chemical, and mechanical data from the user in real time.

[0093] In some embodiments, the intra-oral device integrates light-based sensors to monitor physiological parameters and detect disease indicators. In some embodiments, a photoplethysmography (PPG) sensor is mounted on a flexible printed circuit board (PCB) embedded in the appliance and positioned against the oral mucosa. In some embodiments, the PPG sensor includes a light emitter and a photodiode detector configured to measure heart rate, blood oxygen saturation (SpO2), and pulse waveform. In some embodiments, the PPG sensor includes a light emitter and a photodiode detector.

[0094] In some embodiments, the sensor output is routed through the PCB to an onboard microcontroller for signal processing.

[0095] In some embodiments, a spectroscopic sensor or fluorescence detector is integrated to detect tissue reflectance or fluorescence changes indicative of oral disease. In someembodiments, the optical sensor includes a near-infrared or Raman spectroscopy element to estimate blood glucose levels non-invasively via absorption or scattering patterns in saliva or tissue. In some embodiments, the appliance includes groove-mounted modules with transparent optical windows that allow light transmission while shielding the sensor from saliva and mechanical forces. In some embodiments, the appliance includes groove-mounted modules with transparent optical windows that allow light transmission while shielding

[0096] In some embodiments, the intra-oral device incorporates motion and biomechanical sensors to track jaw position and movement during use. In some embodiments, an inertial measurement unit (IMU) comprising an accelerometer and a gyroscope is embedded to detect jaw shifts, clenching, and snoring-related motion. In some embodiments, a magnetic jaw tracking system includes a magnet affixed to one tray and a corresponding magnetometer on the opposite tray to monitor mandibular position. In some embodiments, a magnetic jaw tracking system includes a magnet affixed to one tray and a corresponding magnetometer on the opposite

[0097] In some embodiments, the magnetometer calculates real-time advancement, lateral motion, or vertical drop of the mandible during sleep.

[0098] In some embodiments, pressure or force sensors are embedded in the bite surfaces to detect grinding and clenching events. In some embodiments, pressure or force sensors are embedded in the bite surface. In some embodiments, the pressure sensors are positioned at key contact areas such as the molars or canines. In some embodiments, sensors are mounted to a flexible PCB routed through molded grooves or recessed channels in the appliance. In some embodiments, the sensor modules are sealed and protected from saliva while maintaining tissue contact and positional integrity.

[0099] In some embodiments, the device includes salivary biochemical sensors for detecting analytes such as hormones, cytokines, and metabolites. In some embodiments, the sensors are mounted in regions of the appliance with reliable saliva access, such as the sublingual area or molar region. In some embodiments, the sensors are mounted in regions of the appliance with reliable saliva access, such as the sublingual area. In some embodiments, a cortisol sensor includes an electrochemical biosensor with cortisol-specific antibodies or aptamers generating an electrical response based on hormone concentration. In some embodiments, the sensor measures circadian fluctuations in cortisol to assess stress levels. Insome embodiments, additional sensors target hormones such as estrogen, testosterone, or fertility markers using immunoassay or optical detection. In some embodiments, cytokine sensors detect inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), or C-reactive protein (CRP). In some embodiments, cytokine sensors detect inflammatory markers. In some embodiments, microfluidic channels are formed within the appliance to direct saliva to the sensing surfaces. In some embodiments, semi-permeable membranes are used to protect sensor electrodes while allowing selective analyte diffusion.

[0100] In some embodiments, metabolite sensors such as glucose or uric acid sensors are integrated into grooves of the appliance and coupled to on-board electronics for real-time analysis. In some embodiments, metabolite sensors such as glucose or uric acid sensors are integrated into grooves of the device. In some embodiments, the biochemical sensor insert is removable or replaceable to maintain sensor accuracy and hygiene.

[0101] In some embodiments, the intra-oral device includes a microcontroller or control circuit that processes sensor data using embedded algorithms or communicates wirelessly with external devices. In some embodiments, machine learning models are used to analyze data from optical, mechanical, and chemical sensors to detect health-related events. In some embodiments, on-device algorithms classify events such as apneic episodes, bruxism, irregular heart rate, or biomarker fluctuations. In some embodiments, on-device algorithms classify events such as apneic episodes and bruxism. In some embodiments, adaptive sampling routines are implemented, increasing sampling frequency in response to detected physiological anomalies. In some embodiments, the control module adjusts sensor timing or prioritizes power consumption based on Al-detected conditions. In some embodiments, sensor data trends are used to optimize mandibular advancement settings or generate alerts if therapeutic efficacy declines. In some embodiments, sensor data trends are used to optimize mandibular advancement settings or generate alerts.

[0102] In some embodiments, the appliance includes a mechanical adjustment mechanism or alert interface to prompt user- or clinician-directed treatment changes. In some embodiments, a wireless transceiver transmits data to a paired smartphone or hub device, which forwards the data to a cloud-based analytics platform.

[0103] In some embodiments, the cloud system applies more complex Al models to evaluate user health trends, detect risks, or generate personalized reports. In someembodiments, the cloud system applies more complex Al models to evaluate user health trends. In some embodiments, a physician-facing dashboard allows remote monitoring of sleep quality, stress, inflammation, or therapy compliance metrics. In some embodiments, the Al system can push software updates to the device or smartphone to improve performance and personalization over time.

[0104] In some embodiments, the sensor comprises a pulse oximetry module that includes a light emitter and photodetector for measuring oxygen saturation levels (SpO2) based on red and infrared light absorption. The sensor may be configured to contact, or be in close proximity to, thin mucosal tissue with minimal melanin interference, such as the inner lip or sublingual area, to enhance signal fidelity.

[0105] In some embodiments, a plurality of PPG sensors or a combination of PPG and electrocardiogram (ECG) sensors are placed in different locations within the oral cavity. These sensors can be used to calculate pulse transit time (PTT) or pulse wave velocity (PWV), which may correlate with blood pressure or arterial stiffness.

[0106] In some embodiments, the device includes a temperature sensor configured to measure core body temperature via oral mucosa or sublingual tissues. The sensor may use thermistors, infrared sensors, or thermal resistive elements in continuous or sampled modes.

[0107] In some embodiments, the sensor comprises a bio-impedance sensor or capacitive element to assess hydration status or electrolyte balance based on dielectric properties of oral mucosa or saliva.

[0108] In some embodiments, a galvanic skin response (GSR) sensor or skin conductance sensor is integrated into the intra-oral device to detect stress markers or sympathetic nervous system activity via oral mucosa.

[0109] In some embodiments, the device includes a multi -wavelength sensor array (e.g., 3-10 distinct LEDs and matching detectors) that performs spectral analysis of tissue chromophores, enabling simultaneous estimation of parameters such as oxygenation, hydration, and metabolic state.

[0110] In some embodiments, the sensor data is analyzed using an onboard or cloud-based machine learning algorithm to adaptively adjust sampling rates, sensor sensitivity, or alert thresholds based on the user’s physiological patterns and history.[OHl] In some embodiments, manufactured products provided in certain embodiments include intra-oral or dental devices. These products may feature a flexible sensor positioned on, adhered to, or implanted in the outer surface of the intra-oral device , ensuring close contact with a patient’s soft or hard tissues (e.g., tooth structure) when the device is placed in the patient's mouth or oral cavity. The flexible sensor, though flexible, may have fixed dimensions and may be located within a slot, groove, or inset on the device's surface. Additionally, the device's surface curvature may align with that of a dental arch.

[0112] Some embodiments may incorporate a data storage capability or unit linked to the flexible sensor, with options including a data storage feature integrated into a Radio Frequency Identity (RFID) chip or Near-Field Communication (NFC) chip.

[0113] In some embodiments, the slot, groove, or insert included in the device may have a depth ranging from about 0.5 to about 15 mm, for example, about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, or about 10 mm. Additionally, in some embodiments, in manufactured products, the maximum distance from the sensor (such as a flexible sensor or an inflexible, flat, or non-curved sensor) to the outer surface or soft or hard tissue of the patient can be between about 0.5 mm to about 5 mm, e.g., less than about 1 mm, resulting in more precise physiological measurements.

[0114] In some embodiments, the sensor, whether flexible or inflexible, may encompass various types, functions, and measurement capabilities, including photoplethysmography (PPG) sensors, physiological sensors, physical sensors, chemical sensors, proximity sensors, vibration sensors, positional sensors, or combinations thereof.

[0115] The present disclosure relates to a device, wherein the sensor device includes a flexible portion. The present disclosure relates to a device, wherein the sensor device includes an inflexible portion. The present disclosure relates to a device, wherein the sensor device includes a pivot. The present disclosure relates to a device, wherein the sensor device includes a plurality of flexible portions. The present disclosure relates to a device, wherein the sensor device includes at least three flexible portions. The present disclosure relates to a device, wherein the sensor device includes a plurality of inflexible portions. The present disclosurerelates to a device, wherein the sensor device includes a plurality of pivots. The present disclosure relates to a device, wherein the sensor device includes at least three pivots. The present disclosure relates to a device, wherein the sensor device includes at least three bend points. The present disclosure relates to a device, wherein the sensor device is bendable to be inserted into the device. The present disclosure relates to a device, wherein the sensor device includes a bend point. The present disclosure relates to a device, wherein the sensor device includes a plurality of bend points. For example, FIG. 2 illustrates a sensor device with three different bend points in some embodiments. In some embodiments, bend points can be flexible or pivotable. In some embodiments, using flexible circuit board that has more than 1 bend point, e.g., can allow a circuit to be inserted based on a patient specific oral structure.

[0116] FIG. 3 illustrates flexible circuit board configurations as a sensor device for an arch form with changed radiuses to allow insertion of a flexible sensor circuit board as a sensor device in some embodiments. In some embodiments, the flexible circuit board configuration is also designed and manufactured to follow the patient’s dental arch (mandibular and / or maxillary), for example, by varying radius of circuit board slot cut, for example, as illustrated in FIG. 3.

[0117] In some embodiments, materials for manufacturing the sensor, whether flexible or inflexible, may include silicone, plastic (possibly acetate), liquid crystal polymer (LCP) substrate, LCP base material with cladding (possibly thin copper cladding), fiber or yam, paper (potentially containing cellulose nanofibers (CNFs), polyaniline nanofiber / graphite nanofiber (PANI / GNF) nanocomposite, polyaniline (PANI) supportive matrix deposited on an optical fiber core acting as an active cladding), vinylidene fluoride-trifluoroethylene- hexafluoroacetone copolymer, or combinations thereof.

[0118] Some embodiments may involve manufactured products or intra-oral devices functioning as mandibular advancement devices (MADs), orthodontic devices, or intra-oral devices repositioning the mandible or maxilla.

[0119] In some embodiments, provided are products of manufacture, or intra-oral or dental devices, for example, orthodontic devices and mandibular advancement devices (MADs), having flexible sensors positioned on surface of the dental device such that the flexible sensor follows or is in close contact with the curved (or non-straight) contour of a patient’s hard orsoft tissues; and by being able to follow the contours of the patient’s hard or soft tissue the flexible sensor is able to take more accurate readings of the patient’s physiologic state.

[0120] For example, in some embodiments, photoplethysmography (PPG) sensors can be used in products of manufacture, or intra-oral or dental devices, for example, as provided herein to measure volumetric variations of blood circulation, and because PPG sensors use optical measurements using a light source and a photodetector at the surface of skin to measure and monitor volumetric variations of blood circulation and heart rate, having the PPG follow the contour of a patient’s soft tissues results in relatively more accurate measurements.

[0121] In some embodiments, using a PPG mounted or placed on a flexible sensor allows measurement of physiological data with greater precision.

[0122] In some embodiments, provided are products of manufacture manufactured as an intra-oral or dental device. In some embodiments, the product of manufacture may comprise a flexible sensor positioned on or adhered to or implanted in an outer surface of the intra-oral device configured such that the flexible sensor in is substantially complete, close contact with a patient’s soft tissue or hard tissue (e.g., a tooth structure) when the intra-oral device is positioned or placed in the mouth or the oral cavity of the patient. In some embodiments, the sensor, while flexible, may not be expandable or stretchable (i.e., the sensor while flexible otherwise has a fixed dimension). In some embodiments, the product of manufacture may comprise and the flexible sensor is positioned in or substantially within a slot, groove or inset, on a surface of the intra-oral device . In some embodiments, the product of manufacture may comprise an inflexible, or flat, or non-curved sensor positioned on a curved surface of the intra- oral device . In some embodiments, the product of manufacture may comprise a sensor positioned in or substantially within a slot, groove or inset, on a surface of the intra-oral device , and optionally the curve of the surface of the intra-oral device substantially follows the curve of a dental arch.

[0123] In some embodiments, the product of manufacture may comprise a data storage capability or data storage unit operably linked to or connected to the flexible sensor, optionally a data storage capability built into a Radio Frequency Identity (RFID) chip or Near-Field Communication (NFC) chip.

[0124] In some embodiments, the slot, groove or inset is between about 0.5 to 15 mm deep, e.g., about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm deep, about 6 mm, about7 mm, about 8 mm, about 9 mm or about 10 mm deep. In some embodiments, in the products of manufacture, a maximum length from the sensor, such as a flexible sensor, or an inflexible, or flat, or non-curved sensor, to the outer surface of the product of manufacture, or soft or hard tissue of the patient, is less than about 1 mm, for example, between about 0.5 mm to about 5 mm, e.g., about 0.5 mm, about 1 mm, about 2 mm, about 3 mm, or about 4 mm, resulting in measurements by the sensor, such as a flexible sensor, or an inflexible, or flat, or non-curved sensor, of physiologic data with relatively greater precision than if the flexible sensor, or the inflexible, or flat, or non-curved sensor, were not in substantially close contact with the soft or hard tissue of the patient.

[0125] In some embodiments, the sensor, such as a flexible sensor, or an inflexible, or flat, or non-curved sensor may include a variety of types of sensors, with various functions and various measurement capabilities. For example, in some embodiments, the sensor may be a photoplethysmography (PPG) sensor, a physiological sensor, a physical sensor, a chemical sensor, a proximity sensor, vibration sensor, a positional sensor, or a combination thereof.

[0126] In some embodiments, the sensor, such as a flexible sensor, or an inflexible, or flat, or non-curved sensor may be manufactured using a silicone, plastic (optionally, an acetate), a liquid crystal polymer (LCP) substrate, an LCP base material adhered to a cladding (optionally a thin copper cladding), a fiber or a yam, paper (optionally comprising cellulose nanofibers (CNFs), a polyaniline nanofiber / graphite nanofiber (PANI / GNF) nanocomposite, a polyaniline (PANI) supportive matrix (optionally deposited on a core of optical fiber which acts as an active cladding), a vinylidene fluoride-trifluoroethylene-hexafluoroacetone copolymer, or a combination thereof.

[0127] In some embodiments, the product of manufacture or the intra-oral device may be a mandibular advancement device (MAD) or an orthodontic device, or an intra-oral device that repositions the mandible or the maxilla.

[0128] The details of one or more exemplary embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.

[0129] All publications, patents, patent applications cited herein are hereby expressly incorporated by reference in their entireties for all purposes.

[0130] The present disclosure relates to a device, wherein the protruding portion is protruding in a first direction substantially away from a surface of the sensor device. The present disclosure relates to a device, wherein the protruding portion is protruding in a second direction substantially parallel to a surface of the sensor device. The present disclosure relates to a device, wherein the protruding portion is protruding in a second direction different from the first direction. The present disclosure relates to a device, wherein the protruding portion is protruding in a second direction substantially parallel to the surface of the sensor device. The present disclosure relates to a device, wherein the protruding portion is protruding from a surface of the sensor by about 0.1 mm to about 10 mm. The present disclosure relates to a device, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 7 mm. The present disclosure relates to a device, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 5 mm. The present disclosure relates to a device, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 4 mm. For example, FIG. 4 illustrates a protruding portion protruding with respect to a surface of a sensor device in some embodiments. Referring to FIG. 4, the protruding portion protrudes in a first direction (z direction shown) by about 3.5 mm. The protruding portion protrudes in a second direction (with respect to y axis) by about 2 mm. In some embodiments, adding offset values in XYZ to maximize skin contact to improve signal strength.

[0131] In some embodiments, a sensor such as a Photoplethysmography (PPG) sensor can be mounted in or on a flexible circuit board such as a Printed Circuit Board Assembly (PCBA), For example, FIG. 5 illustrates a Photoplethysmography (PPG) sensor as a sensor that is mounted in or on a Printed Circuit Board Assembly (PCBA) for an intra-oral device as an intra-oral device in some embodiments. In some embodiments, products of manufacture, or intra-oral or dental devices, as provided herein, are configured as illustrated in FIG. 5, where a PPG sensor is mounted in or on a flexible circuit board. Referring to FIG. 5, the products of manufacture, or intra-oral or dental devices, as an intra-oral device , can be labeled as a brace. Both the outer surface and the inner surface of the product of manufacture, or brace, can be curved or contoured to substantially follow the curvature or variations of the patient’s soft tissue. In some embodiments, the soft tissue may include various types of soft tissue inside of the mouth or the oral cavity, including any soft tissue adjacent or between the teeth, including but not limited to the papilla, tissue of the upper and lower dental arches, marginal gingiva, gingival sulcus, inter-dental gingiva, gingival gum structure on lingual and buccal surfaces upto and including the muco-gingival junction and / or the palate and / or the floor of the mouth. In some embodiments, the soft tissue area may include the muco-buccal folds, hard and soft palates, lining mucosa, the tongue and / or attached gingival tissue. In some embodiments, the inner surface of the brace as the intra-oral device may be pressed close to the tooth. In some embodiments, the other surface of the brace as the intra-oral device can face toward the upper lip. In some embodiments, the upper lip covers the outer surface of the intra-oral device , substantially providing no space in between the upper lip and the outer surface of the intra-oral device . In some embodiments, the maximum length from the sensor to the outer surface of the intra-oral device as the brace can be less than 1mm. In some embodiments, a groove as a recess is comprised in the intra-oral device . In some embodiments, the width of the groove can be about 2 mm, e.g., 2.1 mm.

[0132] In some embodiments, the flexible circuit board with the sensor or sensors (such as a PPG or any other sensor) can be placed in a groove or inset cut or otherwise designed into either / or the outer surface of the product of manufacture. In some embodiments, the width of the groove or insert can be from about 0.5 mm to about 10 mm, such as about 2.1 mm, about 3 mm, etc. In some embodiments the depth of the inset, slot or groove is between about 0.5 to 15 mm deep, or is about 1 mm, 2 mm, 3 mm, 4 mm, 5 mm deep, 6 mm, 7 mm, 8 mm, 9 mm or 10 mm deep. For example, FIG. 5 illustrates a flexible circuit board with the sensor or sensors placed in a groove or inset cut or slot, or otherwise designed into either / or the outer surface of an intra-oral device as a product of manufacture in some embodiments. An exemplary product of manufacture having an inset, slot or groove is illustrated in FIG. 5.

[0133] In some embodiments, the patient’s soft tissue, for example, the mucosa of the inside of the lips, or soft tissue of the cheek, rest against the outer surface of the product of manufacture. In some embodiments, the product of manufacture can be designed such that there is no space, or minimal space, or substantially no space (for example, between about 0.5 mm and about 5 mm), between the outer surface of the product of manufacture and the patient’s soft tissue. In some embodiments, this is accomplished by designing the outer surface of the product of manufacture to have a curvature that is substantially the same as the curvature of the patient’s soft tissue. In some embodiments, because of the curved design of the product of manufacture and the flexible sensor, the maximum length from the sensor (a PPG in this example) to the outer surface of the product of manufacture (or brace) is less than about 1 mm(or is between about 0.25 and 1.5 mm), resulting in measurements of physiological data with greater precision.

[0134] In some embodiments, the sensor is an optical device or member (for example, can be a light source or light meter or light detecting element, such as for example a LED light source or LED detecting element).

[0135] In some embodiments, the sensor or the flexible circuit board configuration may not follow the curvature of the product of manufacture (for example, the exemplary intra-oral dental device does not follow the arch curvature, i.e., the sensor or the flexible circuit board is flat as compared to the intra-oral dental device that substantially follows the curve of the dental arch), for example, as illustrated by the exemplary intra-oral device as a product of manufacture shown in FIG. 4, which shows a flat LED light source. In some embodiments, by not following the curvature of the product of manufacture, for example, not following the arch curvature, the sensor (for example, a PPG sensor area), or a LED light source (for example, the flat or noncurved sensor, light source, light meter), has a stronger signal (as compared to a curved or nonflat equivalent); and this configuration may deter light and / or signal from spreading out and helps returned light signal to be stronger; this will increase device signal precision.

[0136] In some embodiments, the flexible sensor can be between about 1 and 40 mm or 2 and 20 mm in length, and the flexible sensor is in close contact with, or actually contacts, a patient’s hard or soft tissue substantially most of the length of the flexible sensor. In some embodiments, the flexible sensor is between about 1 and 10 mm or 2 and 20 mm in width, and the flexible sensor is in close contact with, or actually contacts, a patient’s hard or soft tissue substantially most of the length and width of the flexible sensor.

[0137] In some embodiments, the product of manufacture, or intra-oral or dental device, as provided herein, can have data storage capability (or data storage unit). In some embodiments, the sensor (for example, a PPG sensor) can be operatively linked or connected to data storage capability (or a data storage unit), and the sensor sends measurements to the data storage unit, which retains this data, and optionally the data storage unit transfers the data in real time, or at a later designated time, for example, in the morning when the data is accrued during the night to a remote source, for example, by wireless communication, for example, using near-field communication (NFC) and / or Bluetooth (BLE) technologies, including for example, a NFC communication module and an NFC antenna. In some embodiments, this exemplary datatransfer method can allow a minimized battery size, one benefit of which is improved patient comfort by having a smaller sized battery and thus a smaller sized intra-oral product of manufacture. Wireless communication can be in the form of a radio, an infrared, or magnetic communication.

[0138] In some embodiments, monitoring of data from the sensors can be continuous (or always on) or can be sampled at a regular frequency (for example, between 0.001 Hz and 1 KHz, between 1 and 120 times / hour, between 1 and 24 time / day, etc.) or can be sampled for a discrete time after inserting the apparatus. In some embodiments, monitoring may comprise monitoring over a time period of greater than one day (for example, more than: 24 hours, 36 hours, 48 hours, 3 days, 4 days, 5 days, etc.). In some embodiments, monitoring may be continuous (for example, at periodic intervals, e.g. 100 Hz, 10 Hz, 1 Hz, 1 / min, every 2 min, every 3 min, every 5 min, every 10 min, every 30 min, every hour, etc.) or at discrete intervals (for example, when requested by a user, etc.).

[0139] In some embodiments, the wireless communication can be in various forms, such as in the form of a radio, an infrared, a magnetic communication and / or near field communication (NFC), including NFC-to-NFC communication, for example, Wi-Fi, radio (RF, UHF, etc.), infrared (IR), microwave, Bluetooth (including Bluetooth low energy or BLE), magnetic field induction (including for example NFC), Worldwide Interoperability for Microwave Access (WiMAX), zigbee (a standards-based wireless technology that enables low- cost, low-power wireless machine-to-machine (M2M) and internet of things (loT) networks) and / or ultrasound.

[0140] In some embodiments, systems as provided herein may comprise a monitoring apparatus with a first antenna within a housing of a near field communication (NFC) to Bluetooth communication (e.g., BLE) signal coupler device, transmitting the monitoring data from the monitoring apparatus to the NFC to BLE signal coupler device by NFC, and retransmitting the monitoring data from the NFC to BLE signal coupler device via a Bluetooth signal to a handheld electronic device. In some embodiments, systems as provided herein may comprise inserting the monitoring apparatus into the NFC to BLE signal coupler device, wherein the NFC to BLE signal coupler device is configured as a case configured to hold the monitoring apparatus (or MA and a dental appliance to which the monitoring apparatus is coupled). In some embodiments, systems as provided herein may comprise receiving the Bluetooth signal in the handheld electronic device, wherein the handheld electronic devicecomprises a smartphone. In some embodiments, systems as provided herein may comprise modifying the monitoring data before retransmitting the data, and transmitting the monitoring data may comprise receiving the NFC signal comprising the monitoring data on a first antenna of the NFC to BLE signal coupler device. In some embodiments, retransmitting the monitoring data may comprise transmitting the monitoring data as the Bluetooth data via a second antenna of the NFC to BLE signal coupler device configured for Bluetooth communication.

[0141] In some embodiments, the sensor and the data storage capability are operatively linked or connected to a power source, such as a battery, such as a lithium-ion battery or a lithium-thionyl chloride battery. In some embodiments, the battery is a rechargeable or replaceable battery, and can also comprise a battery recharging circuit compatible with industry standards.

[0142] In some embodiments, products of manufacture, or intra-oral or dental device, as provided herein, comprise in addition to a power source: an on-board memory, a communication module, an analog / digital converter, a control module for activating stepper motors, and / or an I / O bus to connect to external components.

[0143] In some embodiments, the data storage capability (or data storage unit), for example, a data storage capability built into a Radio Frequency Identity (RFID) chip or NearField Communication (NFC) chip, comprises for memory an Electronic Product Code (EPC) memory, which is a writeable memory to store an EPC code having a minimum potential of 96 bits. In some embodiments, the data storage capability is a reserved memory designed to lock the reading and writing activities of a radio frequency identity (RFID) chip, for example, an ultra-high-frequency (UHF) RFID. In some embodiments, the data storage capability can also comprise tag identifier (TID) memory, a read-only memory (ROM), to differentiate one tag from another. In some embodiments, the data storage capability can comprise a second writable memory bank that allows users to read already entered data, and write more data through an RFID or NFC reader.

[0144] In some embodiments, the product of manufacture, or intra-oral or dental device, as provided herein, may comprise a rechargeable or removable power source and one or more coupling coils arranged in a power / communication circuit such that the power source can provide electrical power for exciting coupling coils. Exciting coils can create a magnetic field that can reach one or more sensors; and, a coil and / or an antenna can be excited by theelectromagnetic field generated by coupling coils, which induces a current in the coil / antenna. Through inductive coupling, the induced current can be used to power the sensor for an extended period of time. For example, a rechargeable battery can provide as much as eight hours of power to a sensor through this inductive coupling configuration.

[0145] In some embodiments, the product of manufacture, or intra-oral or dental device, as provided herein, comprises an external recharging device that incorporates wireless charging functionality by way of a wireless charging / coupling pad or coil incorporated into housing of an external recharging cradle to re-charge the product of manufacture, or intra-oral or dental device. Current from an internal or external power source can flow through the coil / pad inside recharging device creating an electromagnetic field, and the electromagnetic field can induce current in a coupling coil (for example, an inductive coupling) of the product of manufacture, or intra-oral or dental device, that is in electrical communication with the battery. Such current can recharge the battery of the intra-oral appliance. As such, the external recharging device can provide wireless recharging of the remote controller of the product of manufacture, or intra- oral or dental device.

[0146] In some embodiments, the external recharging device can also provide gentle ultrasonic or chemical cleaning of the teeth covering of the product of manufacture, or intra- oral or dental device. The cleaning can be similar to other ultrasonic or chemical -based cleaning system. The external recharging device can include a display that indicates that the charging and cleaning function is either “off,” “in progress” or “complete” by way of a multi-color indicator, for example. The wireless recharging function can provide a complete charge in 120 minutes using a 5 V, 2A power source, for example.

[0147] In some embodiments, a miniaturized radio transponder and radio receiver and transmitter assembly, such as a radio frequency identity (RFID or NFC) chip, operatively connected or linked to a miniature antenna to wirelessly transmit, and optionally also receive, data (such as instructions) to and from a remote device (or base) such as a computer (such as a laptop computer or a desktop computer), a smart tablet, or a phone, such as a smart phone, which can have software, optionally software on an app; where optionally the data is read and instructions are given back to the product of manufacture by a medical professional, for example, a dentist.

[0148] In some embodiments, the base analyzes the wirelessly received data and, based on a pre-scripted routine or program, relays a command to the product of manufacture, or intraoral device , such as a MAD, to take an action in response. In some embodiments, wherein the product of manufacture, or intra-oral device , such as a MAD, further comprises a motor, and the action comprises a communication to the motor from the base to activate a change in the positional relationship of an upper (maxillary) splint positioned on the upper dentition to the lower (mandibular) splint positioned on the lower dentition. In some embodiments, the at least one sensor comprises a communication component configured for wireless communication with a base, and the base and the intra-oral device operate in a feedback system, and when data obtained by the at least one sensor is communicated with the base, the base analyzes the data and, based on a pre-scripted routine, relays a command to the intra-oral device to take an action in response, and the action comprises a communication to the motor from the base to activate a change in the positional relationship of the upper splint positioned on the upper dentition to the lower splint positioned on the lower dentition.

[0149] In some embodiments, the product of manufacture, or intra-oral device , such as a MAD, as provided herein, comprises elements to record data, and transmit recorded data to storage for review and analysis, where the transferred data may be subjected to downloading, validation, storage, analysis, measuring, database fusion, data output, and data recording. Output may be further transferred to a computer, processor, phone, tablet computer, or other hardware for review by a user or technical, research, medical, or other oversight personnel; data also can be transmitted to the product of manufacture, including firmware or other onboard operating instructions.

[0150] In some embodiments, provided are systems (or multiplex systems) comprising a product of manufacture, or intra-oral device , such as a MAD, as provided herein, and one or more computers or devices loaded with a set of computer-executable instructions. The computers or devices may be general purpose computers, special-purpose computers, or other programmable data processing apparatus to produce a particular machine, such that the one or more computers or devices are instructed and configured to carry out required calculations, processes, steps, operations, algorithms, statistical methods, formulas, or computational routines to practice methods as provided herein. The computer or device performing the specified calculations, processes, steps, operations, algorithms, statistical methods, formulas, or computational routines may comprise at least one processing element such as a centralprocessing unit (or processor) and a form of computer-readable memory which may include random-access memory (RAM) or read-only memory (ROM). The computer-executable instructions can be embedded in computer hardware or stored in computer-readable memory such that the computer or device may be directed to perform one or more of the calculations, steps, processes and operations.

[0151] In some embodiments, the system as provided herein that comprises a computer (for example, a desktop computer, a portable computer, such as a tablet, laptop, PDA, or smartphone, or a set of computers) is also operably connected to a network including a clientserver configuration and one or more database servers. The network may use any suitable network protocol, including IP, UDP, or ICMP, and may be any suitable wired or wireless network including any local area network, wide area network, Internet network, telecommunications network, Wi-Fi enabled network, or Bluetooth enabled network. In one embodiment, the computer system comprises a central computer connected to the internet that has computer-executable instructions stored in memory that is operably connected to an internal electronic database. The central computer may perform the computer-implemented method based on input and commands received from remote computers through the internet. The central computer may effectively serve as a server and the remote computers may serve as client computers such that the server-client relationship is established, and the client computers issue queries or receive output from the server over a network.

[0152] In some embodiments, a system as provided herein also comprises a graphical user interface (GUI) which may be used in conjunction with computer-executable code and electronic databases. The graphical user interface may allow a user to perform these tasks through the use of text fields, check boxes, pull-downs, command buttons, and the like; and graphical features may be implemented for performing methods as provided herein. The user interface may optionally be accessible through a computer connected to the internet. In one embodiment, the user interface is accessible by typing in an internet address through an industry standard web browser and logging into a web page. The user interface may then be operated through a remote computer (for example, a computer operated by a dentist) accessing the web page and transmitting queries or receiving output from a server through a network connection.

[0153] In some embodiments, the product of manufacture, or intra-oral device , such as a MAD, as provided herein, comprises one or more flexible sensors, wherein the sensor can bea photoplethysmography (PPG) sensor, a physiological sensor, a physical sensor, a chemical sensor, a proximity sensor, vibration sensor, or a positional sensor.

[0154] In some embodiments, the physiological sensor detects and measures patient physiological parameters (data) comprising for example: blood sugar, blood oxygen levels, body temperature, respiration rate and / or heart rate.

[0155] In some embodiments, the physical sensor is able to detect and measure: vibration in the breathing, airflow rate, oxygen concentration of inhaled air, carbon dioxide concentration of exhaled air, atmospheric pressure, air pressure inside the patient’s oral cavity, noise, pressure exerted on the MAD by the patient’s teeth, and / or actigraphic data (actigraphic measurements comprise sleep parameters and average motor activity using a noninvasive accelerometer).

[0156] In some embodiments, the chemical sensor detects and measures: saliva pH, saliva glucose concentration, saliva conductivity, stress markers, salivary cortisol, blood oxygen saturation level, blood pH, blood glucose levels, blood insulin levels, and / or inflammatory markers.

[0157] In some embodiments, the positional sensor detects and records a position of the product of manufacture, or intra-oral device , such as a MAD, in a mouth with respect to a predetermined reference location.

[0158] In some embodiments, a proximity sensor can comprise one or more of a capacitive sensor, an eddy-current sensor, a magnetic sensor, an optical sensor, a photoelectric sensor, an ultrasonic sensor, a Hall Effect sensor, an infrared touch sensor, or a surface acoustic wave (SAW) touch sensor, and the one or more proximity sensors may be configured to generate sensing data when in proximity to one or more of the patient’s enamel, gingiva, oral mucosa, cheeks, lips, or tongue; and the one or more proximity sensors may be integrated with an intra- oral device or appliance as provided herein, coupled to a soft tissue or a tooth, or a combination thereof. In some embodiments,

[0159] In some embodiments, a vibration sensor comprises one or more of: a MEMS microphone, an accelerometer, or a piezoelectric sensor; and intra-oral vibration patterns may be associated with one or more of: vibrations transferred to the patient’s teeth via the patient’s jaw bone, teeth grinding, speech, mastication, breathing, or snoring; and the processor may determine whether the intra-oral appliance is being worn by comparing the intra-oral vibrationpatterns to patient-specific intra-oral vibration patterns; and the one or more vibration sensors may be integrated with the intra-oral appliance, coupled to a tooth, or a combination thereof; and the processor can be integrated with the intra-oral device or appliance as provided herein or coupled to soft tissue or a tooth.

[0160] In some embodiments, the flexible sensor comprises: a touch or tactile sensor such as a capacitive or resistive sensor, a proximity sensor, an audio sensor (for example, a microelectromechanical system (MEMS) microphone), a color sensor (for example, a RGB color sensor), an electromagnetic sensor (for example, a magnetic reed sensor, a magnetometer), a light sensor, a force sensor (for example, a force-dependent resistive materials), a pressure sensor, a temperature sensor, a motion sensor (for example, an accelerometer and / or a gyroscope), a vibration sensor, a piezoelectric sensor, a strain gauge, a pH sensor, a conductivity sensor, a gas flow sensor, a gas detection sensor, a humidity or moisture sensor, a physiological sensor (for example, an electrocardiography sensor, a bioimpedance sensor, a photo-plethysmography sensor, a galvanic skin response sensor), or combinations thereof.

[0161] In some embodiments, motion sensors comprise or are designed as accelerometers, gyroscopes, piezoelectric film vibration sensors, gravity sensors, microwave emitters and / or receivers. The motion sensors can be integrated into a product of manufacture (such as an intra- oral appliance) as provided herein worn on a patient’s upper or lower jaw, or can be distributed across an appliance worn on the upper jaw and an appliance worn on the lower jaw. In some embodiments, the motion sensors are configured to generate data representative of the patient’s jaw movement patterns, and the monitoring device processes and analyzes the movement patterns (for example, using power spectrum and / or kinematic analysis) to determine whether the patterns indicate that the appliance(s) are being worn. In some embodiments, the monitoring sensor can distinguish jaw movement patterns associated with different oral activities (for example, mastication, grinding, speech, etc.).

[0162] In some embodiments, flexible sensors as used in products of manufacture as provided herein are operatively connected to or configured as a switch that is activated and / or deactivated in response to a particular type of signal or stimulus such as an optical, electrical, magnetic and / or mechanical signal or stimulus.

[0163] In some embodiments, the flexible sensor is manufactured using a silicone, plastic (for example, an acetate) or liquid crystal polymer (LCP) substrate (see for example, Wang et al Polymers (Basel) (2018) Jul; 10(7): 694) base material adhered to a cladding such as a thin copper cladding, a fiber or a yam (see for example, Li et al nano micro Small vol. 18(7) (2022)), paper (such as cellulose nanofibers (CNFs) or paper, see for example, Liu et al, J. Materials Chem. 10(10)), a polyaniline nanofiber / graphite nanofiber (PANI / GNF) nanocomposite (for example, see Mohammed et al IEEE Access, vol. 9, pg 145282 (2021), or a polyaniline (PANI) supportive matrix which can be deposited on a core of optical fiber which acts as an active cladding (see for example, Pahurkar et al, Measurement, Vol. 61, February 2015, Pg 9-15). In some embodiments, the flexible sensor is manufactured using a cladding material comprising a vinylidene fluoride-trifluoroethylene-hexafluoroacetone copolymer (see for example, EP88308227B1). The disclosures of the foregoing references are incorporated herein by reference in their entireties.

[0164] In some embodiments, the flexible sensor is manufactured using (or comprises) an electroconductive medical polymer such as: acrylic, acrylonitrile butadiene styrene (ABS), polycarbonate / acrylonitrile-butadiene-styrene terpolymer blend (PC / ABS), acetyl, polycarbonate, polyolefins such as polypropylene (PP) and polyethylene (PE) and other resin systems, polymers rendered electrically conductive, such as acetals such as polyoxymethylene (POM), acrylics such as poly(methyl methacrylate) (PMMA), fluoropolymers such as polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF) and perfluoroalkoxy alkanes (PF A), polycarbonate (PC) and PC alloys, polyethereketone (PEEK), polyolefins (PP), (PE), and polymethylpentene (PMP), polysulfone (PSU), polyethersulfone (PES), thermoplastic polyurethane elastomer (TPUR), and styrenics polystyrene (PS) and ABS. In some embodiments, the polymer comprises polypyrrole (PPy), polyaniline (PANI), poly(3,4- ethylenedi oxy thiophene) (PEDT, PEDOT), polythiophene (PTh), polythiophene-vinylene (PTh-V), poly(2,5-thienylenevinylene) (PTV), poly(3 -alkylthiophene) (PAT), poly(p- phenylene) (PPP), poly-p-phenylene-sulphide (PPS), poly(p-phenylenevinylene) (PPV), poly(p-phenylene-terephthalamide) (PPTA), polyacetylene (PAc), poly(isothianaphthene) (PITN), poly(a-naphthylamine) (PNA), polyazulene (PAZ), polyfuran (PFu), polyisoprene (PIP), polybutadiene (PBD), and / or poly(3-octylthiophnene-3- methylthiophene) (POTMT); or, a PERMASTAT PLUS™ polymer, or as described in U.S. Pat. No. 8,685,461.

[0165] In some embodiments, the product of manufacture comprising the flexible sensor as provided herein is any intra-oral device , such as an orthodontic device, or a MAD, and in some embodiments the MAD is manufactured, designed and / or used as has been described in for example: U.S. patent nos. (USPN) 11,617,677; 11,291,580; 11,207,207.

[0166] In some embodiments, the product of manufacture is made using three- dimensional (3D) printing and / or a computer aided design (CAD) computer program, for example comprising a method comprising: a) importing into a computer aided design (CAD) computer program a digitized data set obtained from a three-dimensional scan of a patient’s dentition; b) preparing a three-dimensional electronic model of the patient’s dentition; c) subtracting the three-dimensional electronic model of the patient’s dentition from an image of a solid block to obtain an appliance data set; and d) manufacturing a dental appliance in accordance with the appliance data set. In some embodiments, the volume of the solid block correlates to the volume of the sensor or shaped to be sufficient to encompass the sensor.

[0167] In some embodiments, the product of manufacture is made using three-1dimensional (3D) printing and / or a computer aided design (CAD) computer program, for example comprising a method comprising: a) preparing a three-dimensional electronic model of the flexible printed circuit board; b) importing into a computer aided design (CAD) computer program the three-dimensional electronic model of the flexible printed circuit board; c) subtracting the three-dimensional electronic model of the flexible printed circuit board from the appliance data set to create the custom slot in the device for the physical flexible circuit board, creating a male / female mirroring between the device slot and the physical flexible circuit board to facilitate proper sensor positioning and manufacturing assembly.

[0168] In some embodiments, the product of manufacture is manufactured from a polymer, a composite, a thermoplastic, a thermoset, and the like. In some embodiments, the appliance is subtractively manufactured from a block of, or additively manufactured to form, a material selected from the group consisting of standard polymethylmethacrylate (PMMA), lined PMMA, high-strength polyetheretherketone (PEEK), polymer produced from polyoxymethylene and acetal copolymers (DURACETAL®), glycol modified polyethylene terephthalate (PETg), and a physiologically compatible, water insoluble, non-malleable polymer, wood, and metal.

[0169] In some embodiments, the product of manufacture is manufactured in whole or in part from a polymer, a composite, a thermoplastic, a thermoset, and the like. In some embodiments, the appliance is subtractively manufactured from a block of, or additively manufactured to form, a material comprising: poly(butylene succinate) and copolymers thereof; polymethyl-methacrylate (PMMA); lined PMMA; high-strength polyether ether ketone (PEEK); a (meth)acryloyloxy-substituted benzoic acid ester; urethane di(meth)acrylate (UDMA); triethyleneglycol dimethacrylate (TEGDMA); tetraethylene glycol diacrylate (E4- A); trimethylolpropanetriacrylate (TTA); a polymer matrix comprising diurethanedimethacrylate (DUDMA) and glycerol dimethacrylate (GDMA); a polymer produced from polyoxymethylene and acetal copolymers (DURACETAL®); glycol modified polyethylene terephthalate (PETg); a physiologically compatible, water insoluble, non- malleable polymer; wood; plastic, and / or, a metal.

[0170] In some embodiments, the product of manufacture is manufactured suing an extrusion, and can be designed in CAD, or is designed and then merged together in CAD to make a desired and complete product of manufacture (for example, a MAD or a splint). In some embodiments, the designed feature of the product of manufacture comprises a standard and well-defined geometrical shape, for example a cube, a pyramid, a cone, a cylinder. A well- defined geometrical shape is one in which the cross section of a feature of the product of manufacture is a standard geometrical shape of a circle, a square, a rectangle, a parallelogram, a circle, a triangle, a rhombus, and the like. In other embodiments, a feature of the product of manufacture comprises a customized shape. The customized shape is one in which the cross section is a non-standard, or amorphous, geometrical shape. In some embodiments, a feature is entirely made up of one, or a merger of two or more, standard geometrical shapes. In other embodiments, a feature of the product of manufacture is entirely made up of one, or a merger of two or more, non- standard geometrical shapes. In other embodiments, the feature comprises between 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90% of one or more standard geometrical shape(s), with the remainder being comprised of one or more non-standard shape(s). In other embodiments, a feature of the product of manufacture (for example, a tapered offset) is adjusted in an iterative process of addition and subtraction (for example at least two cycles of addition and subtraction) until an optimized design (e.g., a taper that fits the patient’s dentition very well) is obtained. The artisan of ordinary skill understands that while the above processes are given an example for illustration, the design processes can be used with any feature of the product of manufacture or their accessories.

[0171] FIG. 5 illustrates an orthodontic device with a sensor pocket and a circuit channel design in some embodiments. Referring to FIG. 5, the orthodontic device can include a patient specific circuit design, for example, based on a relative position of a recess or a protrusion such as a sensor pocket and different bend points.Kits

[0172] Provided are kits comprising products of manufacture and systems (for example, multiplexed systems) for practicing methods as provided herein; and optionally, and kits can further comprise instructions for practicing methods as provided herein.

[0173] Any of the above aspects and embodiments can be combined with any other aspect or embodiment as disclosed here in the Summary, Figures and / or Detailed Description sections.

[0174] As used in this specification and the claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.

[0175] Unless specifically stated or obvious from context, as used herein, the term “or” is understood to be inclusive and covers both “or” and “and”.

[0176] Unless specifically stated or obvious from context, as used herein, the term “about” is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean. About (use of the term “about”) can be understood as within 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12% 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from the context, all numerical values provided herein are modified by the term “about.”

[0177] Unless specifically stated or obvious from context, as used herein, the terms “substantially all”, “substantially most of’, “substantially all of’ or “majority of’ encompass at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%, or more of a referenced amount of a composition; or in some embodiment, when the curve of the surface of the intra-oral device substantially follows the curve of a dental arch, the curve of the surface of the intra-oral device can have one or some sections of the device that do not exactly or closely follow the curve of a dental arch but 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5% of the intra-oral device does follow the curve of a dental arch.NON-LIMITING EMBODIMENTS

[0178] The following Examples are detailed by way of illustration only and are not to be construed as limiting in spirit or in scope, many modifications both in materials and in methods will be apparent to those skilled in the art.1. An oral device comprising: a device body configured to couple to dentition; and a sensor device configured to couple to the device body, the sensor device comprising a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.2. A device comprising: a device body configured to couple to dentition; and a sensor device configured to couple to the device body, the sensor device comprising a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.3. A device comprising: a device body configured to couple to dentition; and a sensor device configured to couple to the device body, the sensor device comprising a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be protruded in an oral cavity when the device body couples to the dentition.4. The device of embodiment 1-3, wherein the protruding portion is to contact the tissue when the device body couples to the dentition.5. The device of embodiment 1-3, wherein the protruding portion is to press the tissue when the device body couples to the dentition.6. The device of embodiment 1-3, wherein the protruding portion is to push the tissue when the device body couples to the dentition.7. The device of embodiment 1-3, wherein the protruding portion is to press the tissue within the oral cavity when the device body couples to the dentition.8. The device of embodiment 1-3, wherein the protruding portion is to push the tissue within the oral cavity when the device body couples to the dentition.9. The device of embodiment 1-6, wherein the protruding portion comprises the sensor.10. The device of embodiment 1-9, wherein the tissue comprises soft tissue.11. The device of embodiment 1-9, wherein the tissue comprises oral mucosa.12. The device of embodiment 1-9, wherein the tissue comprises buccal mucosa.13. The device of embodiment 1-9, wherein the tissue comprises a region of buccal mucosa closer to a maxillary arch than to a lip.14. The device of embodiment 1-9, wherein the tissue comprises a region of buccal mucosa closer to a mandibular arch than to a lip.15. The device of embodiment 1-9, wherein the tissue comprises gingiva.16. The device of embodiment 1-9, wherein the tissue comprises palate.17. The device of embodiment 1-9, wherein the tissue comprises a lip.18. The device of embodiment 1-9, wherein the tissue comprises an oral mucosa around a upper lip.19. The device of embodiment 1-9, wherein the tissue comprises an oral mucosa around a lower lip.20. The device of embodiment 1-9, wherein the tissue comprises an oral mucosa above a upper lip.21. The device of embodiment 1-9, wherein the tissue comprises an oral mucosa below a lower lip.22. The device of embodiment 1-9, wherein the tissue comprises a region of oral mucosa closer to a maxillary arch than to a lip.23. The device of embodiment 1-9, wherein the tissue comprises a region of oral mucosa closer to a mandibular arch than to a lip.24. The device of embodiment 1-9, wherein the tissue comprises a tongue.25. The device of embodiment 1-9, wherein the tissue comprises a tooth.26. The device of embodiment 1-9, wherein the tissue comprises retromolar trigone.27. The device of embodiment 1-9, wherein the tissue comprises tonsil.28. The device of embodiment 1-9, wherein the tissue comprises uvla.29. The device of embodiment 1-9, wherein the tissue comprises a floor of mouth.30. The device of embodiment 1-9, wherein the tissue comprises buccal mucosa around a lip.31. The device of embodiment 1-9, wherein the tissue comprises buccal mucosa around a cheek.32. The device of embodiment 1-31, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition.33. The device of embodiment 16, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive the obtained information.34. The device of embodiment 1-31, wherein the sensor is configured to detect a signal from the adjacent tissue when the device body couples to the dentition.35. The device of embodiment 34, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the signal.36. The device of embodiment 1-31, wherein the sensor is configured to sense a parameter from the adjacent tissue when the device body couples to the dentition.37. The device of embodiment 36, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the parameter.38. The device of embodiment 1-31, wherein the sensor is configured to sense a condition of the adjacent tissue when the device body couples to the dentition.39. The device of embodiment 38, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the condition.40. The device of embodiment 1-31, wherein the sensor is configured to sense a condition of the adjacent tissue when the device body couples to the dentition.41. The device of embodiment 40, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the condition.42. The device of embodiment 1-31, wherein the sensor is configured to sense a physiological condition of the adjacent tissue when the device body couples to the dentition.43. The device of embodiment 42, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive information associated with the physiological condition.44. The device of embodiment 33, 35, 37, 39, 41, 43, wherein the receiving device is disposed outside the oral cavity.45. The device of embodiment 33, 35, 37, 39, 41, 43, wherein the receiving device is disposed outside the oral cavity.46. The device of embodiment 1-45, wherein the sensor is configured to be coupled to the device to sense through an outer surface of the device.47. The device of embodiment 1-46, wherein the sensor device is configured to contact the tissue.48. The device of embodiment 1-47, wherein the sensor is configured to be positioned to be close to the tissue.49. The device of embodiment 1-48, wherein the sensor device comprises a flexible portion.50. The device of embodiment 1-48, wherein the sensor device comprises a flexible portion to be deformed.51. The device of embodiment 1-48, wherein the sensor device comprises a flexible portion to be deformed when the device couples to the dentition.52. The device of embodiment 1-48, wherein the sensor device comprises a flexible portion to be deformed when the sensor device contacts the dentition.53. The device of embodiment 1-49, wherein the sensor device comprises an inflexible portion.54. The device of embodiment 1-53, wherein the sensor device comprises a pivot.55. The device of embodiment 1-54, wherein the sensor device comprises a plurality of flexible portions.56. The device of embodiment 1-55, wherein the sensor device comprises at least three flexible portions.57. The device of embodiment 1-56, wherein the sensor device comprises a plurality of inflexible portions.58. The device of embodiment 1-57, wherein the sensor device comprises a plurality of pivots.59. The device of embodiment 1-58, wherein the sensor device comprises at least three pivots.60. The device of embodiment 1-59, wherein the sensor device comprises a bend point.61. The device of embodiment 1-60, wherein the sensor device comprises a plurality of bend points.62. The device of embodiment 1-61, wherein the sensor device comprises at least three bend points.63. The device of embodiment 1-62, wherein the sensor device is bendable to be inserted into the device.64. The device of embodiment 1-63, wherein the protruding portion is protruding in a first direction substantially away from a surface of the sensor device.65. The device of embodiment 1-63, wherein the protruding portion is protruding in a second direction substantially parallel to a surface of the sensor device.66. The device of embodiment 64, wherein the protruding portion is protruding in a second direction different from the first direction.67. The device of embodiment 64, wherein the protruding portion is protruding in a second direction substantially parallel to the surface of the sensor device.68. The device of embodiment 1-67, wherein the protruding portion is protruding from a surface of the sensor by about 0.1 mm to about 10 mm.69. The device of embodiment 1-67, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 7 mm.70. The device of embodiment 1-67, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 5 mm.71. The device of embodiment 1-67, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 4 mm.72. The device of embodiment 1-71, wherein the device includes a recess or a protrusion on a surface of the device, and wherein the sensor device is configured to be coupled to the recess or the protrusion.73. The device of embodiment 72, wherein the recess include the protrusion to push the sensor device against the tissue.74. The device of embodiment 72, wherein the recess or the protrusion includes a slot, a groove, or an insert, and wherein the sensor device is configured to be coupled to the slot, the groove, or the insert.75. The device of embodiment 1-74, wherein the device includes a curved surface.76. The device of embodiment 75, wherein the curved surface of the device corresponds to a curve of a dental arch in the oral cavity.77. The device of embodiment 1-76, wherein the sensor device includes data storage operably linked to or connected to the sensor.78. The device of embodiment 77, wherein the data storage is built into a Radio Frequency Identity (RFID) chip or Near-Field Communication (NFC) chip.79. The device of embodiment 1-78, wherein a maximum distance between a surface of the sensor facing toward the tissue and an outer surface of the device is from about 0.01 mm to about 5 mm.80. The device of embodiment 1-79, wherein the sensor is a photoplethysmography (PPG) sensor, a physiological sensor, a physical sensor, a chemical sensor, a proximity sensor, a vibration sensor, or a positional sensor.81. The device of embodiment 1-80, wherein the sensor includes a silicone, plastic, a liquid crystal polymer (LCP) substrate, an LCP base material adhered to a cladding, a fiber or a yarn, paper (optionally comprising cellulose nanofibers (CNFs), a polyaniline nanofiber / graphite nanofiber (PANI / GNF) nanocomposite, or a polyaniline (PANI) supportive matrix, or a combination thereof.82. The device of embodiment 1-81, wherein the device is a mandibular advancement device (MAD), or an orthodontic device, or a device that repositions a mandible or a maxilla.83. A method comprising coupling an oral device to dentition, wherein the device comprises:a device body configured to couple to the dentition; and a sensor device configured to couple to the device body, the sensor device comprising a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.84. A method comprising coupling a device to dentition, wherein the device comprises: a device body configured to couple to the dentition; and a sensor device configured to couple to the device body, the sensor device comprising a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.85. A method comprising coupling a device to dentition, wherein the device comprises: a device body configured to couple to the dentition; and a sensor device configured to couple to the device body, the sensor device comprising a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be protruded in an oral cavity when the device body couples to the dentition.

[0179] The entirety of each patent, patent application, publication and document referenced herein hereby is incorporated by reference. Citation of the above patents, patent applications, publications and documents is not an admission that any of the foregoing is pertinent prior art, nor does it constitute any admission as to the contents or date of these publications or documents. Incorporation by reference of these documents, standing alone, should not be construed as an assertion or admission that any portion of the contents of any document is considered to be essential material for satisfying any national or regional statutory disclosure requirement for patent applications.

[0180] Notwithstanding, the right is reserved for relying upon any of such documents, where appropriate, for providing material deemed essential to the claimed subject matter by an examining authority or court.

[0181] Modifications may be made to the foregoing without departing from the basic aspects of the invention. Although the invention has been described in substantial detail with reference to one or more specific embodiments, those of ordinary skill in the art will recognize that changes may be made to the embodiments specifically disclosed in this application, and yet these modifications and improvements are within the scope and spirit of the invention. The invention illustratively described herein suitably may be practiced in the absence of any element(s) not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising”, “consisting essentially of’, and “consisting of’ may be replaced with either of the other two terms. Thus, the terms and expressions which have been employed are used as terms of description and not of limitation, equivalents of the features shown and described, or portions thereof, are not excluded, and it is recognized that various modifications are possible within the scope of the invention. Embodiments of the invention are set forth in the following claims.

[0182] A number of embodiments of the invention have been described. Nevertheless, it can be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.

Claims

WHAT IS CLAIMED IS:

1. A device comprising: a device body configured to couple to dentition; and a sensor device configured to couple to the device body, the sensor device comprising a sensor and a protruding portion protruding from a surface of the sensor device to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.

2. The device of claim 1, wherein the protruding portion is to press the tissue when the device body couples to the dentition.

3. The device of claim 1-2, wherein the protruding portion comprises the sensor.

4. The device of claim 1-3, wherein the tissue comprises buccal mucosa.

5. The device of claim 1-3, wherein the tissue comprises a region of oral mucosa closer to a maxillary arch than to a lip.

6. The device of claim 1-3, wherein the tissue comprises oral mucosa around a lip.

7. The device of claim 1-3, wherein the tissue comprises buccal mucosa around a cheek.

8. The device of claim 1-7, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition.

9. The device of claim 8, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive the obtained information.

10. The device of claim 9, wherein the receiving device is disposed outside the oral cavity.

11. The device of claim 1-10, wherein the sensor device is configured to contact the tissue.

12. The device of claim 1-11, wherein the sensor device comprises a plurality of pivots.

13. The device of claim 1-11, wherein the sensor device comprises a plurality of bend points.

14. The device of claim 1-13, wherein the protruding portion is protruding in a first direction substantially away from a surface of the sensor device.

15. The device of claim 1-14, wherein the protruding portion is protruding from a surface of the sensor by about 0.1 mm to about 10 mm.

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