Methods for sensing physiological change and related devices

Abstract

A method may comprise obtaining a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level, obtaining a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time, comparing the dot product value to a threshold, and, based on the comparison of the dot product value to a threshold value, removing the two signal values from the tow signals, respectively.

Description

METHODS FOR SENSING PHYSIOLOGICAL CHANGE AND RELATED DEVICESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This international application claims priority to U.S. Provisional Application No. 63 / 761,821, entitled, “METHODS FOR SENSING PHYSIOLOGICAL CHANGE AND RELATED DEVICES”, filed February 21, 2025, which is hereby incorporated herein by reference as if set forth in full.TECHNICAL FIELD

[0002] This invention generally relates to methods for sensing a physiological change and related devices such as devices to be placed inter-orally, and related methods for making and using.BACKGROUND

[0003] Dental devices such as orthodontic devices and mandibular advancement devices (MAD) have a long residence time 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.DESCRIPTION OF DRAWINGS

[0004] 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.

[0005] FIG. 1A illustrates an example soft and hard tissues in an oral cavity in some embodiments.

[0006] FIG. IB illustrates an example pulse oximeter diagram in some embodiments.

[0007] FIG. 2 illustrates a sensor device with three different bend points in some embodiments.

[0008] 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.

[0009] FIG. 4 illustrates a protruding portion protruding with respect to a surface of a sensor device in some embodiments.

[0010] FIG. 5 illustrates an orthodontic device with a sensor pocket and a circuit channel design in some embodiments.

[0011] FIGs. 6A and 6B illustrate an dental device as an orthodontic device with a PPG sensor coupled to a surface of the orthodontic device in some embodiments.

[0012] FIG. 7 illustrates example PPG light signals measured by a sensor in some embodiments.

[0013] FIG. 8 illustrates the relationship between Signal Alignment Index (SAI) and a threshold over time in some embodiments.

[0014] FIG. 9 illustrates a pulse rate (PR) measurements over time based on a PPG sensor in some embodiments.

[0015] FIG. 10 illustrates distribution of airflow event- and 02 event-triggered sleep apnea-specific hypoxic burden in some embodiments.

[0016] FIG. 11 illustrates an 02 event-triggered method of calculating sleep apneaspecific hypoxic burden that uses a moving window to determine oxygen saturation baseline correlates highly with the airflow event-triggered SASHB in some embodiments.

[0017] FIG. 12 illustrates Bland-Altman analysis in some embodiments.DETAILED DESCRIPTION

[0018] In some aspects, the techniques described herein relate to measuring, estimating or calculating oxygen level in a subject body such as a blood oxygen level.

[0019] For example, SpCh is the functional oxygen saturation measured by pulse oximetry. Functional oxygen saturation, which also can be referred to as functional oxygen saturation of arterial hemoglobin, is the fraction of effective hemoglobin, calculated based on or using a mathematical relationship such as the equation HbO2 / [Hb+HbO2]. Functional oxygen saturation is a measure of oxy- and deoxy -hemoglobin and can exclude hemoglobin species such as carboxyhemoglobin or methemoglobin.

[0020] In some aspects, the techniques described herein relate to an application or an algorithm for computing SpCh. In some aspects, the techniques described herein relate to an application or an algorithm for Signal Alignment Index (SAI). In some aspects, the techniques described herein relate to an application or an algorithm for Pulse Rate. In some aspects, the techniques described herein relate to measuring, estimating or calculating oxygen level in a subject body such as a blood oxygen level.

[0021] In some embodiments, a pulse oximeter is a medical device used to measure the oxygen saturation level in the blood, as well as the pulse rate (PR).

[0022] In some aspects, the techniques described herein relate to an application or an algorithm for computing SpCh based on an pulse oximeter. In some aspects, the techniques described herein relate to an application or an algorithm for Signal Alignment Index (SAI) based on an pulse oximeter. In some aspects, the techniques described herein relate to an application or an algorithm for Pulse Rate based on an pulse oximeter.

[0023] In some aspects, the techniques described herein relate to an application or an algorithm for computing SpCh using a pulse oximeter. In some aspects, the techniques described herein relate to an application or an algorithm for Signal Alignment Index (SAI) using a pulse oximeter. In some aspects, the techniques described herein relate to an application or an algorithm for Pulse Rate using a pulse oximeter.

[0024] In some embodiments, an intraoral oximeter device consists of a reflectance pulse oximeter sensor embedded in the maxillary arch, which is patient-specific and manufactured to the prescriber’s prescription

[0025] In some aspects, the techniques described herein relate to an application or an algorithm for computing SpCh . In some aspects, the techniques described herein relate to an application or an algorithm for computing SpCh based on an intraoral oximeter. In some aspects, the techniques described herein relate to an application or an algorithm for Signal Alignment Index (SAI) based on an intraoral oximeter. In some aspects, the techniques described herein relate to an application or an algorithm for Pulse Rate based on an intraoral oximeter.

[0026] In some aspects, the techniques described herein relate to an application or an algorithm for computing SpCh using an intraoral oximeter. In some aspects, the techniques described herein relate to an application or an algorithm for Signal Alignment Index (SAI) using an intraoral oximeter. In some aspects, the techniques described herein relate to an application or an algorithm for Pulse Rate using an intraoral oximeter.

[0027] In some aspects, the techniques described herein relate to a method including: obtaining a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level; obtaining a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time; comparing the dot product value to a threshold; and, based on the comparison of the dot product value to a threshold value, removing the two signal values from the tow signals, respectively.

[0028] In some aspects, the techniques described herein relate to a method, wherein the plurality of light waves are waves reflected from a skin surface.

[0029] In some aspects, the techniques described herein relate to a method, wherein the plurality of signals is obtained based on data generated by a device including: a device body configured to couple to dentition; and a sensor device configured to couple to the device body.

[0030] In some aspects, the techniques described herein relate to a method, wherein the sensor device includes 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.

[0031] In some aspects, the techniques described herein relate to a method, wherein the protruding portion is to press the tissue when the device body couples to the dentition.

[0032] In some aspects, the techniques described herein relate to a method, 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 method, wherein the protruding portion includes the sensor. In some aspects, the techniques described herein relate to a method, wherein the tissue includes buccal mucosa. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a region of buccal mucosa closer to a maxillary arch than to a lip. In some aspects, the techniques described hereinrelate to a method, wherein the tissue includes gingiva. In some aspects, the techniques described herein relate to a method, wherein the tissue includes palate. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a lip. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a tongue. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a tooth. In some aspects, the techniques described herein relate to a method, wherein the tissue includes retromolar trigone. In some aspects, the techniques described herein relate to a method, wherein the tissue includes tonsil. In some aspects, the techniques described herein relate to a method, wherein the tissue includes uvla. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a floor of mouth. In some aspects, the techniques described herein relate to a method, wherein the tissue includes buccal mucosa around a lip. In some aspects, the techniques described herein relate to a method, wherein the tissue includes buccal mucosa around a cheek. In some aspects, the techniques described herein relate to a method, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition.

[0033] In some aspects, the techniques described herein relate to a method, 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 method, wherein the receiving device is disposed outside the oral cavity. In some aspects, the techniques described herein relate to a method, wherein the sensor is configured to be coupled to the device to sense through an outer surface of the device.

[0034] In some aspects, the techniques described herein relate to a method, wherein the sensor device is configured to contact the tissue. In some aspects, the techniques described herein relate to a method, wherein the sensor is configured to be positioned to be close to the tissue.

[0035] In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a flexible portion. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes an inflexible portion. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a pivot. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a plurality of flexible portions. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes at least three flexible portions. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a plurality of inflexible portions.

[0036] In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a plurality of pivots. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes at least three pivots. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a bend point. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a plurality of bend points. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes at least three bend points.

[0037] In some aspects, the techniques described herein relate to a method, wherein the sensor device is bendable to be inserted into the device. In some aspects, the techniquesdescribed herein relate to a method, 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 method, wherein the protruding portion is protruding in a second direction substantially parallel to a surface of the sensor device.

[0038] In some aspects, the techniques described herein relate to a method, 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 method, wherein the protruding portion is protruding in a second direction substantially parallel to the surface of the sensor device.

[0039] In some aspects, the techniques described herein relate to a method, 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 method, 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 method, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 5 mm.

[0040] In some aspects, the techniques described herein relate to a method, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 4 mm.

[0041] In some aspects, the techniques described herein relate to a method, 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.

[0042] In some aspects, the techniques described herein relate to a method, wherein the recess include the protrusion to push the sensor device against the tissue.

[0043] In some aspects, the techniques described herein relate to a method, 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.

[0044] In some aspects, the techniques described herein relate to a method, wherein the device includes a curved surface.

[0045] In some aspects, the techniques described herein relate to a method, wherein the curved surface of the device corresponds to a curve of a dental arch in the oral cavity.

[0046] In some aspects, the techniques described herein relate to a method, wherein the sensor device includes data storage operably linked to or connected to the sensor.

[0047] In some aspects, the techniques described herein relate to a method, wherein the data storage is built into a Radio Frequency Identity (RFID) chip or Near-Field Communication (NFC) chip.

[0048] In some aspects, the techniques described herein relate to a method, 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.

[0049] In some aspects, the techniques described herein relate to a method, 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.

[0050] In some aspects, the techniques described herein relate to a method, 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 yam, paper (optionally including cellulose nanofibers (CNFs), a polyaniline nanofiber / graphite nanofiber (PANI / GNF) nanocomposite, or a polyaniline (PANI) supportive matrix, or a combination thereof.

[0051] In some aspects, the techniques described herein relate to a method, wherein the device is a mandibular advancement device (MAD), or an orthodontic device, or a device that repositions a mandible or a maxilla.

[0052] For example, in some aspects, the techniques described herein relate to a method for obtaining a hypoxic burden including: identifying an occurrence of a ventilatory disturbance; and calculating the hypoxic burden based on a moving window to determine an oxygen saturation baseline.

[0053] In some aspects, the techniques described herein relate to a method, wherein the hypoxic burden is calculated based on data generated by a device including: a device body configured to couple to dentition; and a sensor device configured to couple to the device body.

[0054] In some aspects, the techniques described herein relate to a method, wherein the sensor device includes 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.

[0055] In some aspects, the techniques described herein relate to a method, 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 method, 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 method, wherein the protruding portion includes the sensor.

[0056] In some aspects, the techniques described herein relate to a method, wherein the tissue includes buccal mucosa. In some aspects, the techniques described herein relate to a method, 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 method, wherein the tissue includes gingiva. In some aspects, the techniques described herein relate to a method, wherein the tissue includes palate. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a lip. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a tongue. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a tooth. In some aspects, the techniques described herein relate to a method, wherein the tissue includes retromolar trigone. In some aspects, the techniques described herein relate to a method, wherein the tissue includes tonsil. In some aspects, the techniques described herein relate to a method, wherein the tissue includes uvla. In some aspects, the techniques described herein relate to a method, wherein the tissue includes a floor of mouth. In someaspects, the techniques described herein relate to a method, wherein the tissue includes buccal mucosa around a lip. In some aspects, the techniques described herein relate to a method, wherein the tissue includes buccal mucosa around a cheek.

[0057] In some aspects, the techniques described herein relate to a method, 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 method, 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 method, wherein the receiving device is disposed outside the oral cavity.

[0058] In some aspects, the techniques described herein relate to a method, 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 method, wherein the sensor device is configured to contact the tissue. In some aspects, the techniques described herein relate to a method, wherein the sensor is configured to be positioned to be close to the tissue. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a flexible portion. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes an inflexible portion. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a pivot. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a plurality of flexible portions. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes at least three flexible portions. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a plurality of inflexible portions.

[0059] In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a plurality of pivots. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes at least three pivots. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a bend point. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes a plurality of bend points. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes at least three bend points.

[0060] In some aspects, the techniques described herein relate to a method, wherein the sensor device is bendable to be inserted into the device. In some aspects, the techniques described herein relate to a method, 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 method, wherein the protruding portion is protruding in a second direction substantially parallel to a surface of the sensor device.

[0061] In some aspects, the techniques described herein relate to a method, 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 method, wherein the protruding portion is protruding in a second direction substantially parallel to the surface of the sensor device.

[0062] In some aspects, the techniques described herein relate to a method, wherein the protruding portion is protruding from a surface of the sensor by about 0.1 mm to about 10mm. In some aspects, the techniques described herein relate to a method, 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 method, 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 method, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 4 mm.

[0063] In some aspects, the techniques described herein relate to a method, 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. In some aspects, the techniques described herein relate to a method, wherein the recess include the protrusion to push the sensor device against the tissue. In some aspects, the techniques described herein relate to a method, 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 method, wherein the device includes a curved surface.

[0064] In some aspects, the techniques described herein relate to a method, wherein the curved surface of the device corresponds to a curve of a dental arch in the oral cavity. In some aspects, the techniques described herein relate to a method, wherein the sensor device includes data storage operably linked to or connected to the sensor. In some aspects, the techniques described herein relate to a method, wherein the data storage is built into a Radio Frequency Identity (RFID) chip orNear-Field Communication (NFC) chip.

[0065] In some aspects, the techniques described herein relate to a method, 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.

[0066] In some aspects, the techniques described herein relate to a method, 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 method, 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.

[0067] In some aspects, the techniques described herein relate to a method, wherein the device is a mandibular advancement device (MAD), or an orthodontic device, or a device that repositions a mandible or a maxilla.

[0068] Intra-oral device s such as dental devices, orthodontic devices and mandibular advancement devices (MAD) have a long residence time 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.

[0069] The present disclosure relates 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 sensordevice to position the sensor to be adjacent to tissue in an oral cavity when the device body couples to the dentition.

[0070] The present disclosure relates to a device, wherein the protruding portion is to press the tissue when the device body couples to the dentition. The present disclosure relates to a device, wherein the protruding portion is to push the tissue when the device body couples to the dentition.

[0071] The present disclosure relates to a device, wherein the protruding portion includes the sensor. The present disclosure relates to a device, wherein the tissue includes buccal mucosa. The present disclosure relates to a device, wherein the tissue includes a region of buccal mucosa closer to a maxillary arch than to a lip.

[0072] The present disclosure relates to a device, wherein the tissue includes gingiva. The present disclosure relates to a device, wherein the tissue includes palate. The present disclosure relates to a device, wherein the tissue includes a lip. The present disclosure relates to a device, wherein the tissue includes a tongue. The present disclosure relates to a device, wherein the tissue includes a tooth. The present disclosure relates to a device, wherein the tissue includes retromolar trigone. The present disclosure relates to a device, wherein the tissue includes tonsil. The present disclosure relates to a device, wherein the tissue includes uvla. The present disclosure relates to a device, wherein the tissue includes a floor of mouth. The present disclosure relates to a device, wherein the tissue includes a buccal mucosa around a lip. The present disclosure relates to a device, wherein the tissue includes a buccal mucosa around a cheek.

[0073] The present disclosure relates to a device, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition. The present disclosure relates to a device, further including a receiving device configured to be operably linked to or connected to the sensor to receive the obtained information. The present disclosure relates to a device, wherein the receiving device is disposed outside the oral cavity. The present disclosure relates to a device, wherein the sensor is configured to be coupled to the device to sense through an outer surface of the device. The present disclosure relates to a device, wherein the sensor device is configured to contact the tissue. The present disclosure relates to a device, wherein the sensor is configured to be positioned to be close to the tissue.

[0074] 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 disclosure relates 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.

[0075] 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. The present disclosure relates to a device, wherein the sensordevice 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.

[0076] 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.

[0077] 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.

[0078] The present disclosure relates 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. The present disclosure relates to a device, wherein the recess include the protrusion to push the sensor device against the tissue.

[0079] The present disclosure relates 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.

[0080] The present disclosure relates to a device, wherein the device includes a curved surface. The present disclosure relates to a device, wherein the curved surface of the device corresponds to a curve of a dental arch in the oral cavity.

[0081] The present disclosure relates to a device, wherein the sensor device includes data storage operably linked to or connected to the sensor. 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.

[0082] 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.

[0083] 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.

[0084] 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), apolyaniline nanofiber / graphite nanofiber (PANI / GNF) nanocomposite, or a polyaniline (PANI) supportive matrix, or a combination thereof.

[0085] 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.

[0086] In some embodiments, it can be useful to allow the MAD 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.

[0087] 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 A 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.

[0088] 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.

[0089] 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.

[0090] 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.

[0091] 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. In some embodiments, PPG sensors may utilize optical measurements to monitor blood circulation and heart rate. In some embodiments, a pulse oximeter may be provided, which is a device used to measure the oxygen saturation level in the blood, as well as the pulse rate (PR).

[0092] 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. For example, in some embodiments, intraoralreflectance pulse oximeter can be provided. 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. In some embodiments, an intraoral oximeter device may comprise a reflectance pulse oximeter sensor coupled to the intra-oral or dental device, e.g., embedded in the maxillary arch, which is patient-specific and manufactured to the prescriber’s prescription.

[0093] For example, FIG. IB illustrates an example pulse oximeter diagram in some embodiments.

[0094] As show in FIG. IB, a Sy stem-On- A-Chip (SoC) Microelectronic Unit (MCU) may be used to turn on photoplethysmography (PPG) sensor when the proximity capacitor sensor detects the objects in contact. Reflective PPG signals can be detected by photo diodes and processed through Analog Front-End (AFE) along with computing algorithm for oxygen saturation and pulse rate values per second. The data are then stored in the flash memory. In some embodiments, low power Bluetooth technology (BLE) is employed to communicate between the sensor and a receiving device, such as a controller, e.g., an application on a smartphone for the sensor control and data transfer.

[0095] In some embodiments, utilizing a PPG mounted on a flexible sensor can enable the precise measurement of physiological data.

[0096] 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.

[0097] 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 orNear-Field Communication (NFC) chip.

[0098] 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 noncurved 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.

[0099] 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.

[0100] 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 deviceincludes 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 disclosure relates 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.

[0101] FIG. 3 illustrates a 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.

[0102] 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.

[0103] Some embodiments may involve manufactured products or intra-oral device functioning as mandibular advancement devices (MADs), orthodontic devices, or intra-oral device s repositioning the mandible or maxilla.

[0104] 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 or soft 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.

[0105] 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 thePPG follow the contour of a patient’s soft tissues results in relatively more accurate measurements.

[0106] In some embodiments, using a PPG mounted or placed on a flexible sensor allows measurement of physiologic data with greater precision.

[0107] 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 noncurved 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.

[0108] 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.

[0109] 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, about 7 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.

[0110] 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.[OHl] 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 acladding (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.

[0112] 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.

[0113] 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.

[0114] All publications, patents, patent applications cited herein are hereby expressly incorporated by reference in their entireties for all purposes.

[0115] 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.

[0116] 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 includevarious 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 up to 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.

[0117] 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.

[0118] 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 physiologic data with greater precision.

[0119] 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).

[0120] 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 curveof 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 non-curved sensor, light source, light meter), has a stronger signal (as compared to a curved or non-flat 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.

[0121] 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.

[0122] 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 data transfer 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. The wireless communication can be in the form of a radio, an infrared, or a magnetic communication.

[0123] 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, efc.) 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, efc.).

[0124] 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.

[0125] 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 device comprises 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.

[0126] 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.

[0127] In some embodiments, product 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.

[0128] 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 Near-Field 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.

[0129] 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 the electromagnetic field generated by coupling coils, which induces a current in the coil / antenna. Through inductive coupling, the induced current can be used to powerthe 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.

[0130] 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.

[0131] 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 5V, 2 A power source, for example.

[0132] 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.

[0133] 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 intra-oral 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.

[0134] 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.

[0135] 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 the computer-executable instructions. The computers or devices may be general purpose computers, or 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 central processing 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 the computer-readable memory such that the computer or device may be directed to perform one or more of the calculations, steps, processes and operations.

[0136] 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 client-server 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 the 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.

[0137] In some embodiments, a system as provided herein also comprises a graphical user interface (GUI) which may be used in conjunction with a 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 userinterface 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.

[0138] 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 be a photoplethysmography (PPG) sensor, a physiological sensor, a physical sensor, a chemical sensor, a proximity sensor, vibration sensor, or a positional sensor.

[0139] 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.

[0140] 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).

[0141] 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.

[0142] 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.

[0143] 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,

[0144] 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 vibration patterns 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.

[0145] 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.

[0146] In some embodiments, motion sensors comprise or are designed as accelerometers, gyroscopes, piezoelectric film vibration sensors, gravity sensors, and 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, efc.).

[0147] 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.

[0148] 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.

[0149] 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.

[0150] In some embodiments, data such as physiological parameters, physical parameters, physiological data, physical data, and other various types of data can be further processed, for example, various types of algorithms to various other forms of data, e.g., transformed data, and data indicating other physiological or physical parameters.

[0151] In some embodiments, Sleep apnea-specific hypoxic burden (SASHB) is a metric predictive of the risk of morbidity and mortality associated with obstructive sleep apnea (OSA). In some embodiments, SASHB can be calculated using the area defined by the desaturation following a ventilatory event. In some embodiments, the metric can also be calculated using only an oximetry signal. In some embodiments, this O2 event-triggered SASHB has been assessed previously using a method that approximates baseline oxygen saturation from the maximum oxygen saturation value that occurs in a period of time, such as 100 seconds prior to the end of a desaturation event. In some embodiments, a valid SASHB can be calculated using a different method for approximating the baseline oxygen saturation.

[0152] In some embodiments, various sources of data can be analyzed. The present disclosure relates to a method for obtaining a hypoxic burden which is the area subtended by the oxygen saturation signal following a ventilatory disturbance. In some embodiments, an algorithm involved for method for obtaining a hypoxic burden can include identifying an occurrence of a ventilatory disturbance and providing a baseline that allows calculation of the area below the ventilatory disturbance curve as the hypoxic burden or the area subtended by the oxygen saturation signal following a ventilatory disturbance. In some embodiments, In some embodiments, the peak value preceding the event can be used. In some embodiments, a method may include calculating a moving baseline that represents the values that would have occurred had the ventilatory disturbance not occurred. In some embodiments, The method obtain a 2 minute moving average of the top 25 percentile of oxygen saturation values. This is a centered moving average; the 2 minute window is centered over the ventilatory disturbance. Ins some embodiments, the method may result in a baseline that constitutes the upper margin of the subtended area that equals the hypoxic burden.

[0153] For example, in some embodiments, data based on home sleep test can be used. In some embodiments, data measured from an oral appliance therapy device, such as devices disclosed in the present disclosure can be used. In some embodiments, sleep apneaspecific hypoxic burden was calculated based on devices disclosed in the present disclosure, which may include airflow triggered events or using a new O2 event-triggered method that approximates baseline oxygen saturation from a moving average window. In some embodiments, sleep apnea-specific hypoxic burden can be calculated relatively accurately using an oximetry signal and a method of approximating baseline oxygen saturation that uses a moving window, e.g., instead of a single peak that precedes a desaturation event. In some embodiments, the ability to calculate sleep apnea-specific hypoxic burden - ametric predictive of OSA-associated risk - accurately using an oximetry signal provides clinicians with the ability to assess the riskiness of a patient’s OSA, either at baseline or following treatment, with minimal instrumentation. Additionally, the ability to estimate a patient’s OSA-associated risk using an oximeter could allow for nightly data monitoring instead of single-night sleep tests, which, for example, can produce an inaccurate assessment of OSA severity due to night-to-night variability and require instrumentation that can be cumbersome for patients.

[0154] 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.

[0155] 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.

[0156] 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.

[0157] 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 modifiedpolyethylene terephthalate (PETg), and a physiologically compatible, water insoluble, non-malleable polymer, wood, and metal.

[0158] 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.

[0159] 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.

[0160] 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.

[0161] FIGs. 6A and 6B illustrate an dental device as an orthodontic device with a PPG sensor coupled to a surface of the orthodontic device in some embodiments. In some embodiments, referring to FIGs. 6A and 6B, the oximeter arch can be worn on the maxillary teeth by the user while sleeping or awake. In some embodiments, the arch can be made from different materials such as medically acceptable materials (e.g., a Medical GradeClear Tritan MX710 copolyester and related material) and can be created using different technologies, such as CAD / CAM technology, which allows for a relatively more precise design and manufacturing of a single piece, ensuring accuracy and consistency in its form and function. In some embodiments, the Oximeter Arch may have a centroid hollow channel for embedding the PCBA with the PPG unit.

[0162] In some embodiments, the sensor may have various structural and other physical mechanism to result in intimate, close, or direct contact between the sensor and a surface in the oral cavity. In some embodiments, the sensor can have a protrusion to press against a surface to the oral cavity. In some embodiments, the protruding feature at the location of the PPG unit is to provide a pressing structure to create, maintain, or ensure intimate contact between the PPG and the buccal mucosa for signals. In some embodiments, the sensor can have an extended bump-out feature at the location of the PPG unit to ensure intimate contact between the PPG and the buccal mucosa for strong signals. In some embodiments, the PPG unit also protrudes in the gingival direction to ensure good contact with the buccal mucosa, minimize ambient light interference, and maintain the low profile for the rest of the arch for patient comfort. In some embodiments, the PPG unit can be located near teeth 6 (cuspid) and 7 (lateral incisor). In some embodiments, the oximeter arch can be arranged as shown in FIGs. 6 A and 6B. In some embodiments, the SpCh and PR values can be obtained using a multi -wavelength Photoplethysmography technique. In some embodiments, the device can emit a plurality of light waves having different spectrums or frequency. In some embodiments, the device can emit light waves of two different wavelengths (e.g., two selected from red, infrared, and green), e.g., through the anterior portion of the buccal mucosa overlying the maxillary arch. In some embodiments, the device can emit light waves of three different wavelengths (red, infrared, and green) through the anterior portion of the buccal mucosa overlying the maxillary arch. In some embodiments, some light will be absorbed by the arterial blood, and some reflected back. In some embodiments, oxygenated hemoglobin absorbs more infrared light and less red light while deoxygenated hemoglobin does the opposite. In some embodiments, when more light can be absorbed, it will reflect less as detected by the photodiode in the PPG unit. In some embodiments, the differences in light absorption and reflection can allow the device to calculate the percentage of oxygen in the blood by comparing the reflection levels detected by the photodiode of lights waves with a plurality of wavelengths, such as the three wavelengths.

[0163] FIG. 7 illustrates example PPG light signals measured by a sensor in some embodiments. Referring to FIG. 7, the PPG light signals measured by the sensor can range from about 1,000,000 to about 2,000,000. In some embodiments, each light signal can contain an alternating component (AC) and a strong offset component like direct current (DC).Algorithm of Calculating SpOi

[0164] In some embodiments, relative displacement between PPG sensor and mucosa skin contact such as patient snoring can produce modulated erroneous signals and result in questionable or inaccurate SpCh values calculated from those signals for the RPMO2 device.

[0165] Accordingly, in some embodiments, the present disclosure is directed to an approach of using dot-product of green and red signals with minimum computationalmemory and power is developed to exclude or flag the questionable data from display or further calculations of physiological parameters.

[0166] In some embodiments, prior to computing a dot product or other alignment metric, each of the plurality of light signals may be preprocessed to isolate a pulsatile component. The preprocessing may include removal of a direct current (DC) component by subtracting a moving average, high-pass filtering, band-pass filtering, detrending, normalization, scaling, smoothing, interpolation, or combinations thereof. In some embodiments, an alternating current (AC) component corresponding to pulsatile blood flow may be extracted prior to computing the alignment metric.

[0167] In some embodiments, the dot product may be computed over a sliding window comprising a plurality of samples rather than a single instantaneous sample. The sliding window may include from about 3 to about 1000 samples, from about 5 to about 500 samples, or from about 10 to about 250 samples. The window may correspond to a duration between about 0.05 seconds and about 5 seconds, about 0.05 seconds and about 1 seconds about 0.5 seconds and about 3 seconds about 0.05 seconds and about 7 seconds about 0.05 seconds and about 10, 20, 30, 40, or 60 seconds depending on sampling rate. The window may be centered on a time point, trailing the time point, or leading the time point.

[0168]

[0169] In some embodiments, the dot product may be computed between normalized signal vectors. Normalization may include dividing each signal vector by its magnitude, its root-mean-square value, its peak-to-peak amplitude, or its standard deviation. In some embodiments, L2 normalization may be applied such that the dot product may represent cosine similarity between the vectors.

[0170] In some embodiments, the dot product may be computed in the time domain. In other embodiments, the dot product or equivalent similarity measure may be computed in the frequency domain, including after application of a Fourier transform, short-time Fourier transform, wavelet transform, or other spectral decomposition method.

[0171] Although certain embodiments describe a dot product-based alignment metric, other similarity metrics may be used in addition to or in place of the dot product. Such metrics may include cosine similarity, Pearson correlation coefficient, normalized crosscorrelation, covariance, projection magnitude, mutual information, phase synchronization index, spectral coherence, magnitude-squared coherence, principal component projection, or combinations thereof.

[0172] In some embodiments, a reference vector may be constructed from one wavelength signal, from a weighted combination of multiple wavelength signals, from a principal component derived from multiple signals, or from a template pulsatile waveform. The alignment metric may be computed between the reference vector and one or more other wavelength signals.

[0173] In some embodiments, the alignment metric may be computed at zero lag or across a range of time lags to account for phase shifts between wavelength signals. The maximum similarity across a range of lags may be selected as the alignment value.

[0174] In some embodiments, the threshold used to determine whether signal values are aligned may be a fixed threshold determined empirically. In other embodiments, the threshold may be adaptive and may be adjusted based on signal amplitude, signal variance, perfusion index, patient-specific calibration data, or historical signal quality data.

[0175] In some embodiments, the threshold may be dynamically updated using a moving average of alignment values, a percentile-based approach, or a machine-learning model trained to distinguish physiologically valid pulsatile signals from motion artifacts.

[0176] In some embodiments, multiple thresholds may be defined, including a first threshold indicating acceptable signal quality and a second threshold indicating high-confidence signal quality. Different downstream processing actions may be performed depending on which threshold may be satisfied.

[0177] In some embodiments, when the alignment metric may fail to satisfy the threshold, the corresponding signal values may be excluded from further calculation of physiological parameters. In other embodiments, rather than removing the signal values, the values may be weighted, attenuated, replaced with interpolated values, flagged for later review, or stored with an associated quality score.

[0178] In some embodiments, the alignment metric may be used to scale the contribution of a given wavelength to a ratio-of-ratios SpCh computation. For example, signal components with low alignment may be multiplied by a factor between 0 and 1 prior to calculating a physiological parameter.

[0179] In some embodiments, a Signal Alignment Index (SAI) may be stored alongside computed physiological values, enabling retrospective filtering or quality-based selection of data.

[0180] In some embodiments, computation of the alignment metric may be selectively performed based on activation of a proximity sensor, detection of tissue contact, or detection of adequate signal amplitude. In some embodiments, light emission duty cycle, LED intensity, or sampling frequency may be modulated based on alignment quality to conserve battery power.

[0181] In some embodiments, if the alignment metric may indicate poor signal quality, computation of SpCh or pulse rate may be temporarily suspended to reduce unnecessary processor usage. In some embodiments, only alignment-qualified samples may be used for physiological calculations, thereby reducing computational load.

[0182] In some embodiments, physiological parameters derived from alignment-qualified signals may be used in a feedback control system to adjust the position of a mandibular advancement device (MAD). For example, if a hypoxic burden or oxygen desaturation metric may exceed a predetermined threshold, a control signal may be transmitted to a motor to incrementally advance or retract a mandibular splint.

[0183] In some embodiments, the adjustment may be gradual, constrained within predefined limits, and performed only after a specified duration of sustained physiological disturbance. In some embodiments, the control system may incorporate trend analysis, rate-of-change detection, or predictive modeling to determine appropriate adjustments.

[0184] In some embodiments, the baseline oxygen saturation used to calculate hypoxic burden may be determined using a moving window ranging from about 30 seconds to about 300 seconds, including from about 60 seconds to about 180 seconds. The window may be centered over a ventilatory disturbance or may precede or follow the disturbance.

[0185] In some embodiments, the baseline may be calculated as a moving average of the top percentile of oxygen saturation values within the window, including the top 10%, 15%, 20%, 25%, or 40% of values. In some embodiments, the baseline may be derived from a polynomial fit, spline fit, weighted regression, or adaptive filtering technique.

[0186] In some embodiments, ventilatory disturbances may be identified using airflow signals, oxygen desaturation characteristics, derivative thresholds, slope criteria, or combinations thereof. In some embodiments, hypoxic burden may be calculated solely from oximetry data without airflow data.

[0187] In some embodiments, any one of the plurality of wavelength signals may serve as a reference signal for alignment purposes. In some embodiments, a composite reference signal may be formed by combining two or more wavelength signals using weighted summation, principal component analysis, or other dimensionality reduction techniques.

[0188] In some embodiments, alignment may be evaluated pairwise between all combinations of wavelength signals, and a composite alignment score may be derived from multiple pairwise metrics.

[0189] In some embodiments, the alignment metric and threshold determination may be supplemented or replaced by a machine-learning classifier trained to distinguish artifact-contaminated signals from physiologically valid signals. The classifier may use features derived from time-domain, frequency-domain, and alignment-based metrics.

[0190] In some embodiments, the alignment metric may serve as one feature among multiple features in a signal quality model, and the output of the model may determine whether to include, exclude, weight, or flag signal segments.

[0191] In some embodiments, the use of vector-based alignment metrics in an intraoral reflectance photoplethysmography configuration may improve signal fidelity in a constrained anatomical environment where motion artifacts, tissue compression, and variable contact pressure may differ from conventional fingertip pulse oximetry. By selectively processing alignment-qualified signal components, the system may improve accuracy of physiological measurements while operating under limited computational memory and power constraints.

[0192] In some embodiments, SpCh calculation is based on the ratio R of the AC to DC component of the red (r) and infrared (ir) PPG reflected signals. In some embodiments, to enhance accuracy, a multi -wavelength approach can be used by incorporating green (g) light into the calculation. In some embodiments, the ratio R is computed using the following equation:> ACrACg . avg(DCtr)ACirACg avg(DCr')where ACr• A Cgis the dot product of signals ACrand Agand avg(DCr) is the mean value of (r), and ACtr• ACgis the dot product of signals Atrand ACgand avg(DCir) is the mean value of (ir).

[0193] If we view ACrand ACgas two vectors. The dot product becomesACrACg= |ACr| |ACa|cos0 (2)Where \ACr| is the magnitude of ACr,is the magnitude of ACgand 0 is the angle between the two vectors.

[0194] If we express the vectors in component form as ACr= (acrii1,' acr1 2^,' acrio3,' s and AC y„ = ( vaco, ac„ , ac &„g ,' ....) JACr• ACa= (acriac„ + acrrtac„ + ac. -.ac., + ....) (3)1yv*1 *2 &2 &3y v y

[0195] When the two vectors of (r) and (ir) light signals are aligned, cos0 = 1. cos0 < 1 when the two light signals are not aligned. It is well-known that (g) light is strongly absorbed by oxyhemoglobin and deoxyhemoglobin in the blood. It has been unexpectedly found that the implementation of a dot product-based algorithm makes the signal and / or analysis process relatively more significantly sensitive to the cardiac cycle and effective to capture the pulsatile component of the blood flow compared to the other light signals.

[0196] For example, many oximeters use green light to compute the pulse rate. In contrast, it has been unexpectedly found that leveraging this phenomenon based on the dot product-based algorithm provide a significant technical solution to the signal processing. For example, As shown in Equations 1 and 2, we are only utilizing red (r) and infrared (ir) signal components aligned to the green light signal for calculation of R , which enables practically ignoring at least some, most, or all of the non-aligned components.In some embodiments, SpOi can be calculated through a predetermined piecewise linear function if the ratio R is measur (ed. The piecewise linear function can be written as m±R + b±for R e [xfl1(R2)m2fl + b2for R e [fl2, fl3) (4)m3R + b3for R e [fl3,R4)

[0197] The piecewise linear function has 3 linear sections with different slopes and constants. The slopes and constants can be obtained by regression of measured SpCh values of a reference pulse oximeter with the measured R values from the sensor.Signal Alignment Index (SAI)

[0198] In some embodiments, a pulse oximeter can face measurement challenges such as motion artifacts, unstable contact between skin and a sensor, etc., which can generate noise or measurement errors or can adversely affect the accuracy of the measured results. In some embodiments, a Signal Alignment Index (SAI) to quantify the signal quality can be provided. In some embodiments, the green light can be based or leveraged for its close correlation with pulse in photoplethysmography. In some embodiments, it has been unexpectedly found that, at least in some cases, e.g., most cases, if the red light alignedwith the green light, the PPG signal quality is good. Otherwise, the PPG signal quality is poor.

[0199] In some embodiments, Eq. 2 can be rewritten asACr• ACgCOS0 = SAI (5)where 1 > cos0 > — 1.

[0200] When SAI = cos0 = 0 , the green and red light signals are relatively substantially aligned, e.g., perfectly aligned, which indicates that the PPG signals are relatively sufficient, reliable, or good.

[0201] FIG. 8 illustrates the relationship between Signal Alignment Index (SAI) and a threshold over time in some embodiments. FIG. 8 The shows that SpO2 in blue is of good data (65% of all data) having SAI>0.85 as the threshold. SpO2 with SAI<0.85 is shown in magenta color. In some embodiments, the threshold values can be determined empirically. In some embodiments, it has been unexpectedly found that a threshold value of from about 0.5 to about 1 related well. In some embodiments, it has been unexpectedly found that a threshold value of from about 0.6 to about 1 related well. In some embodiments, it has been unexpectedly found that a threshold value of from about 0.7 to about 1 related well. In some embodiments, it has been unexpectedly found that a threshold value of from about 0.75 to about 0.95 related well for the current applications.

[0202] In some embodiments, a similar approach can be used to calculate SAI between the green and infrared light signals or red and infrared light signals.

[0203] In some embodiments, PR is calculated from the AC component of the green PPG signal that corresponds to pulsatile changes in blood volume. In some embodiments, The device detects the peaks in the green light signal, each peak representing a pulse. In some embodiments, The time intervals between these peaks, known as Inter-Beat Intervals (IBIs), are averaged over a set period of time.

[0204] In some embodiments, In some embodiments, a 2-step process to estimate PR can be implemented. In some embodiments, The first process step uses a small-time step. In some embodiments, The first process step uses a small-time step such as from about 0.01 second to about 1 second, 0.01, from about 0.02 second to about 0.7 second, from about 0.05 second to about 0.5 second, from about 0.1 second to about 0.3 second, such as about 0.01, about 0.02, about 0.03, about 0.05, about 0.07, about 0.1, about 0.15, about 0.2, about 0.25, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, as the minimum time between 2 adjacent peaks to filter out the high frequency noisy pulses in the signal. In some embodiments, for example, the first process step uses a small-time step such as 0.2 second as the minimum time between 2 adjacent peaks to filter out the high frequency noisy pulses in the signal. The estimated initial inter-beat interval (IBIavgl) is computed as the average of IBIs within the preset time interval. A larger time step such as 0.8* IBIavgl is then used in the second process step to find the second averaged IBIavg2. In some embodiments, the second time step is usually larger than the first time step. In some embodiments, the second process step will filter out more high frequency noise than the first process step to arrive ata truer IBI. In some embodiments, the second time step may not be too large that filters out the good signals or totally miss out the searching of peaks. In some embodiments, this iterative progress can be more than 2 steps, and it may produce even better results. In some embodiments, it may require more computing time.

[0205] In some embodiments, PR in the units of beat per minute (BPM) is then computed using the formula:60 secondsPR ='r>'avp2(5)

[0206] In some embodiments, The pulse rate is calculated from the PPG signals shown in at least one of the previous figures and displayed in FIG. 9. FIG. 9 illustrates a pulse rate (PR) measurements over time based on a PPG sensor in some embodiments.Kits

[0207] 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.

[0208] 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.

[0209] As used in this specification and the claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.

[0210] Unless specifically stated or obvious from context, as used herein, the term “or” is understood to be inclusive and covers both “or” and “and”.

[0211] 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.”

[0212] 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 EMBODIMENTS1. A method comprising:obtaining a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level;obtaining a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time;comparing the dot product value to a threshold; andbased on the comparison of the dot product value to a threshold value, removing the two signal values from the two signals, respectively.2. A method for processing physiological optical signals, comprising:obtaining, from a sensor positioned to receive light reflected from tissue of a subject, a plurality of signals corresponding to light waves of different wavelengths over a period of time;determining, based on at least two of the plurality of signals, an alignment metric representing similarity between the at least two signals within a time window; comparing the alignment metric to a threshold; andbased on the comparison, modifying a contribution of at least one of the at least two signals in a calculation of a physiological parameter,wherein the physiological parameter comprises a blood oxygen level or pulse rate.3. A method for estimating a physiological parameter, comprising:obtaining a plurality of optical signals corresponding to light of different wavelengths reflected from biological tissue;computing, using at least two of the plurality of optical signals, a vector-based similarity metric representing alignment between the at least two signals over a plurality of samples; comparing the similarity metric to a signal-quality threshold; andbased on the comparison, selectively controlling processing of at least one of the plurality of optical signals in calculating the physiological parameter,wherein the physiological parameter comprises a blood oxygen level or a pulse rate. 4. A method comprising:obtaining multi -wavelength photoplethysmographic signals;computing a similarity metric between at least two wavelength signals over a plurality of samples;determining a signal quality value based on the similarity metric; andusing the signal quality value to weight, exclude, or adjust at least one wavelength signal in determining a blood oxygen saturation value.5. A method comprising:obtaining multi -wavelength optical signals reflected from tissue;computing a vector-based similarity metric between at least two of the signals, the vectorbased similarity metric comprising a dot product or a normalized projection value; comparing the similarity metric to a threshold; andbased on the comparison, selectively including or excluding signal components in calculating a physiological parameter.6. A method comprising:obtaining a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level;obtaining a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time;comparing the dot product value to a threshold; andbased on the comparison of the dot product value to a threshold value, selectively including or excluding signal components in calculating a physiological parameter. 7. The method of embodiment 1-5, wherein the plurality of light waves are waves reflected from a skin surface.8. The method of embodiment 1-7, wherein the plurality of signals is obtained based on data generated by a device comprising:a device body configured to couple to dentition; anda sensor device configured to couple to the device body.9. The method of embodiment 1-8, wherein the sensor device comprises 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. 10. The method of embodiment 9, wherein the protruding portion is to press the tissue when the device body couples to the dentition.11. The method of embodiment 9, wherein the protruding portion is to push the tissue when the device body couples to the dentition.12. The method of embodiment 9-11, wherein the protruding portion comprises the sensor.13. The method of embodiment 8-12, wherein the tissue comprises buccal mucosa.14. The method of embodiment 8-12, wherein the tissue comprises a region of buccal mucosa closer to a maxillary arch than to a lip.15. The method of embodiment 8-12, wherein the tissue comprises gingiva.16. The method of embodiment 8-12, wherein the tissue comprises palate.17. The method of embodiment 8-12, wherein the tissue comprises a lip.18. The method of embodiment 8-12, wherein the tissue comprises a tongue.19. The method of embodiment 8-12, wherein the tissue comprises a tooth.20. The method of embodiment 8-12, wherein the tissue comprises retromolar trigone.21. The method of embodiment 8-12, wherein the tissue comprises tonsil.22. The method of embodiment 8-12, wherein the tissue comprises uvla.23. The method of embodiment 8-12, wherein the tissue comprises a floor of mouth. 24. The method of embodiment 8-12, wherein the tissue comprises buccal mucosa around a lip.25. The method of embodiment 8-12, wherein the tissue comprises buccal mucosa around a cheek.26. The method of embodiment 8-25, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition. 27. The method of embodiment 26, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive the obtained information. 28. The method of embodiment 27, wherein the receiving device is disposed outside the oral cavity.29. The method of embodiment 8-28, wherein the sensor is configured to be coupled to the device to sense through an outer surface of the device.30. The method of embodiment 8-29, wherein the sensor device is configured to contact the tissue.31. The method of embodiment 8-30, wherein the sensor is configured to be positioned to be close to the tissue.32. The method of embodiment 8-31, wherein the sensor device comprises a flexible portion.33. The method of embodiment 8-32, wherein the sensor device comprises an inflexible portion.34. The method of embodiment 8-33, wherein the sensor device comprises a pivot.35. The method of embodiment 8-34, wherein the sensor device comprises a plurality of flexible portions.36. The method of embodiment 8-35, wherein the sensor device comprises at least three flexible portions.37. The method of embodiment 8-36, wherein the sensor device comprises a plurality of inflexible portions.38. The method of embodiment 8-37, wherein the sensor device comprises a plurality of pivots.39. The method of embodiment 8-38, wherein the sensor device comprises at least three pivots.40. The method of embodiment 8-39, wherein the sensor device comprises a bend point.41. The method of embodiment 8-40, wherein the sensor device comprises a plurality of bend points.42. The method of embodiment 8-41, wherein the sensor device comprises at least three bend points.43. The method of embodiment 8-42, wherein the sensor device is bendable to be inserted into the device.44. The method of embodiment 9-43, wherein the protruding portion is protruding in a first direction substantially away from a surface of the sensor device.45. The method of embodiment 9-43, wherein the protruding portion is protruding in a second direction substantially parallel to a surface of the sensor device.46. The method of embodiment 44, wherein the protruding portion is protruding in a second direction different from the first direction.47. The method of embodiment 44, wherein the protruding portion is protruding in a second direction substantially parallel to the surface of the sensor device.48. The method of embodiment 9-47, wherein the protruding portion is protruding from a surface of the sensor by about 0.1 mm to about 10 mm.49. The method of embodiment 9-47, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 7 mm.50. The method of embodiment 9-47, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 5 mm.51. The method of embodiment 9-47, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 4 mm.52. The method of embodiment 8-51, 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.53. The method of embodiment 52, wherein the recess include the protrusion to push the sensor device against the tissue.54. The method of embodiment 52, 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.55. The method of embodiment 8-54, wherein the device includes a curved surface. 56. The method of embodiment 55, wherein the curved surface of the device corresponds to a curve of a dental arch in the oral cavity.57. The method of embodiment 8-56, wherein the sensor device includes data storage operably linked to or connected to the sensor.58. The method of embodiment 57, wherein the data storage is built into a Radio Frequency Identity (RFID) chip orNear-Field Communication (NFC) chip.59. The method of embodiment 8-58, 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.60. The method of embodiment 8-59, 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.61. The method of embodiment 8-60, 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.62. The method of embodiment 8-61, wherein the device is a mandibular advancement device (MAD), or an orthodontic device, or a device that repositions a mandible or a maxilla.63. A physiological monitoring device comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor operatively coupled to the photodetector and configured to:obtain a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level;obtain a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time;compare the dot product value to a threshold; andbased on the comparison of the dot product value to a threshold value, remove the two signal values from the two signals, respectively.64. A physiological monitoring device comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor operatively coupled to the photodetector and configured to:obtain, from a sensor positioned to receive light reflected from tissue of a subject, a plurality of signals corresponding to light waves of different wavelengths over a period of time;obtain, based on at least two of the plurality of signals, an alignment metric representing similarity between the at least two signals within a time window;compare the alignment metric to a threshold; andbased on the comparison, modify a contribution of at least one of the at least two signals in a calculation of a physiological parameter,wherein the physiological parameter comprises a blood oxygen level or pulse rate.65. A physiological monitoring device comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor operatively coupled to the photodetector and configured to:obtain a plurality of optical signals corresponding to light of different wavelengths reflected from biological tissue;compute, using at least two of the plurality of optical signals, a vector-based similarity metric representing alignment between the at least two signals over a plurality of samples; compare the similarity metric to a signal-quality threshold; andbased on the comparison, selectively control processing of at least one of the plurality of optical signals in calculating the physiological parameter,wherein the physiological parameter comprises a blood oxygen level or a pulse rate. 66. A physiological monitoring device comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor operatively coupled to the photodetector and configured to:obtain multi -wavelength photoplethysmographic signals;compute a similarity metric between at least two wavelength signals over a plurality of samples;determine a signal quality value based on the similarity metric; andprocess the signal quality value to weight, exclude, or adjust at least one wavelength signal in determining a blood oxygen saturation value.67. A physiological monitoring device comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor operatively coupled to the photodetector and configured to:obtain multi -wavelength optical signals reflected from tissue;compute a vector-based similarity metric between at least two of the signals, the vectorbased similarity metric comprising a dot product or a normalized projection value; compare the similarity metric to a threshold; andbased on the comparison, selectively include or exclude signal components in calculating a physiological parameter.68. A physiological monitoring device comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor operatively coupled to the photodetector and configured to:obtain a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level;obtain a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time;compare the dot product value to a threshold; andbased on the comparison of the dot product value to a threshold value, selectively include or exclude signal components in calculating a physiological parameter.69. A physiological monitoring system comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor configured to:obtain a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level;obtain a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time;compare the dot product value to a threshold; andbased on the comparison of the dot product value to a threshold value, remove the two signal values from the two signals, respectively.70. A physiological monitoring system comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor configured to:obtain, from a sensor positioned to receive light reflected from tissue of a subject, a plurality of signals corresponding to light waves of different wavelengths over a period of time;obtain, based on at least two of the plurality of signals, an alignment metric representing similarity between the at least two signals within a time window;compare the alignment metric to a threshold; andbased on the comparison, modify a contribution of at least one of the at least two signals in a calculation of a physiological parameter,wherein the physiological parameter comprises a blood oxygen level or pulse rate.71. A physiological monitoring system comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor configured to:obtain a plurality of optical signals corresponding to light of different wavelengths reflected from biological tissue;compute, using at least two of the plurality of optical signals, a vector-based similarity metric representing alignment between the at least two signals over a plurality of samples; compare the similarity metric to a signal-quality threshold; andbased on the comparison, selectively control processing of at least one of the plurality of optical signals in calculating the physiological parameter,wherein the physiological parameter comprises a blood oxygen level or a pulse rate. 72. A physiological monitoring system comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor configured to:obtain multi -wavelength photoplethysmographic signals;compute a similarity metric between at least two wavelength signals over a plurality of samples;determine a signal quality value based on the similarity metric; andprocess the signal quality value to weight, exclude, or adjust at least one wavelength signal in determining a blood oxygen saturation value.73. A physiological monitoring system comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor configured to:obtain multi -wavelength optical signals reflected from tissue;compute a vector-based similarity metric between at least two of the signals, the vectorbased similarity metric comprising a dot product or a normalized projection value; compare the similarity metric to a threshold; andbased on the comparison, selectively include or exclude signal components in calculating a physiological parameter.74. A physiological monitoring system comprising:a light emitter configured to emit light of a plurality of wavelengths toward biological tissue;a photodetector or sensor configured to detect light reflected from the biological tissue and generate a plurality of corresponding optical signals; anda processor configured to:obtain a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level;obtain a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time;compare the dot product value to a threshold; andbased on the comparison of the dot product value to a threshold value, selectively include or exclude signal components in calculating a physiological parameter.75. The device or system of embodiment 63-74, wherein the plurality of light waves are waves reflected from a skin surface.76. The device or system of embodiment 63-75, wherein the plurality of signals is obtained based on data generated by a device comprising:a device body configured to couple to dentition; anda sensor device configured to couple to the device body.77. The device or system of embodiment 63-76, wherein the sensor device comprises 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.78. The device or system of embodiment 77, wherein the protruding portion is to press the tissue when the device body couples to the dentition.79. The device or system of embodiment 77, wherein the protruding portion is to push the tissue when the device body couples to the dentition.80. The device or system of embodiment 77-79, wherein the protruding portion comprises the sensor.81. The device or system of embodiment 76-80, wherein the tissue comprises buccal mucosa.82. The device or system of embodiment 76-80, wherein the tissue comprises a region of buccal mucosa closer to a maxillary arch than to a lip.83. The device or system of embodiment 76-80, wherein the tissue comprises gingiva. 84. The device or system of embodiment 76-80, wherein the tissue comprises palate. 85. The device or system of embodiment 76-80, wherein the tissue comprises a lip.86. The device or system of embodiment 76-80, wherein the tissue comprises a tongue.87. The device or system of embodiment 76-80, wherein the tissue comprises a tooth. 88. The device or system of embodiment 76-80, wherein the tissue comprises retromolar trigone.89. The device or system of embodiment 76-80, wherein the tissue comprises tonsil.90. The device or system of embodiment 76-80, wherein the tissue comprises uvla.91. The device or system of embodiment 76-80, wherein the tissue comprises a floor of mouth.92. The device or system of embodiment 76-80, wherein the tissue comprises buccal mucosa around a lip.93. The device or system of embodiment 76-80, wherein the tissue comprises buccal mucosa around a cheek.94. The device or system of embodiment 76-93, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition.95. The device or system of embodiment 94, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive the obtained information.96. The device or system of embodiment 95, wherein the receiving device is disposed outside the oral cavity.97. The device or system of embodiment 76-96, wherein the sensor is configured to be coupled to the device to sense through an outer surface of the device.98. The device or system of embodiment 76-97, wherein the sensor device is configured to contact the tissue.99. The device or system of embodiment 76-98, wherein the sensor is configured to be positioned to be close to the tissue.100. The device or system of embodiment 76-99, wherein the sensor device comprises a flexible portion.101. The device or system of embodiment 76-100, wherein the sensor device comprises an inflexible portion.102. The device or system of embodiment 75-100, wherein the sensor device comprises a pivot.103. The device or system of embodiment 75-101, wherein the sensor device comprises a plurality of flexible portions.104. The device or system of embodiment 75-102, wherein the sensor device comprises at least three flexible portions.105. The device or system of embodiment 75-103, wherein the sensor device comprises a plurality of inflexible portions.106. The device or system of embodiment 75-104, wherein the sensor device comprises a plurality of pivots.107. The device or system of embodiment 75-105, wherein the sensor device comprises at least three pivots.108. The device or system of embodiment 75-106, wherein the sensor device comprises a bend point.109. The device or system of embodiment 75-107, wherein the sensor device comprises a plurality of bend points.110. The device or system of embodiment 75-108, wherein the sensor device comprises at least three bend points.111. The device or system of embodiment 75-109, wherein the sensor device is bendable to be inserted into the device.112. The device or system of embodiment 76-110, wherein the protruding portion is protruding in a first direction substantially away from a surface of the sensor device. 113. The device or system of embodiment 76-110, wherein the protruding portion is protruding in a second direction substantially parallel to a surface of the sensor device. 114. The device or system of embodiment 111, wherein the protruding portion is protruding in a second direction different from the first direction.115. The device or system of embodiment 111, wherein the protruding portion is protruding in a second direction substantially parallel to the surface of the sensor device.116. The device or system of embodiment 76-114, wherein the protruding portion is protruding from a surface of the sensor by about 0.1 mm to about 10 mm.117. The device or system of embodiment 76-114, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 7 mm.118. The device or system of embodiment 76-114, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 5 mm.119. The device or system of embodiment 76-114, wherein the protruding portion is protruding from a surface of the sensor by about 1 mm to about 4 mm.120. The device or system of embodiment 75-118, 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.121. The device or system of embodiment 119, wherein the recess include the protrusion to push the sensor device against the tissue.122. The device or system of embodiment 119, 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.123. The device or system of embodiment 75-121, wherein the device includes a curved surface.124. The device or system of embodiment 122, wherein the curved surface of the device corresponds to a curve of a dental arch in the oral cavity.125. The device or system of embodiment 75-123, wherein the sensor device includes data storage operably linked to or connected to the sensor.126. The device or system of embodiment 124, wherein the data storage is built into a Radio Frequency Identity (RFID) chip or Near-Field Communication (NFC) chip.127. The device or system of embodiment 75-125, 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.128. The device or system of embodiment 75-126, 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.129. The device or system of embodiment 75-127, 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.130. The device or system of embodiment 75-128, wherein the device is a mandibular advancement device (MAD), or an orthodontic device, or a device that repositions a mandible or a maxilla.NON-LIMITING EXAMPLE(S)

[0213] The following examples can be provided to illustrate selected embodiments. They should not be considered as limiting the scope of the invention, but merely as being illustrative and representative thereof. Thus, the examples provided below, while illustratedwith a particular medical device or active agent, can be applicable to the range of medical devices and active agents described herein.

[0214] An O2 event-triggered sleep apnea specific hypoxic burden calculator using a novel method for approximating baseline oxygen saturation was validated.

[0215] Purpose:

[0216] Sleep apnea-specific hypoxic burden (SASHB) is a metric predictive of the risk of morbidity and mortality associated with obstructive sleep apnea (OSA). Initially, SASHB was calculated using the area defined by the desaturation following a ventilatory event; however, the metric can also be calculated using only an oximetry signal. This O2 event-triggered SASHB has been assessed previously using a method that approximates baseline oxygen saturation from the maximum oxygen saturation value that occurs in the 100 seconds prior to the end of a desaturation eventl . The purpose of this investigation was to determine if a valid SASHB can be calculated using a different method for approximating the baseline oxygen saturation.

[0217] Methods:

[0218] Data from 152 participants from three prospective clinical studies were analyzed. Study participants completed a two-night level 3 home sleep test at baseline, were treated with an oral appliance therapy device (ProSomnus Sleep Technologies, Pleasanton, CA) that was titrated to achieve an optimal therapeutic effect, then completed another two-night home sleep test. Sleep apnea specific hypoxic burden was calculated on the 605 study nights (baseline and outcome) using a validated calculator that used airflow triggered events and using a new O2 event-triggered method that approximates baseline oxygen saturation from a moving average window3. The two methods of calculating sleep apneaspecific hypoxic burden were compared.

[0219] Results

[0220] FIG. 10 illustrates distribution of airflow event- and O2 event-triggered sleep apnea-specific hypoxic burden in some embodiments.

[0221] FIG. 11 illustrates an O2 event-triggered method of calculating sleep apneaspecific hypoxic burden that uses a moving window to determine oxygen saturation baseline correlates highly with the airflow event-triggered SASHB (r = 0.99) in some embodiments.

[0222] FIG. 12 illustrates Bland- Altman analysis (Bias of 3.0, lower 95% limit of agreement of -16.5, and upper 95% limit of agreement of 22.5) in some embodiments.

[0223] Table 1 illustrates 2x2 table showing the agreement between the two methods using a cutoff of 60%min / h for sleep apnea-specific hypoxic burden in some embodiments.Table 1. Agreement between the two methods using a cutoff of 60%min / h for sleep apneaspecific hypoxic burdenO2triggered < 60 O2triggered > 60 % %min / h min / h Airflow triggered < 60478 6 %min / hAirflow triggered > 605 116%min / h

[0224] Conclusions:

[0225] The results of this investigation indicate that sleep apnea-specific hypoxic burden can be calculated accurately using an oximetry signal and a method of approximating baseline oxygen saturation that uses a moving window instead of a single peak that precedes a desaturation event.

[0226] Clinical Implications:

[0227] The ability to calculate sleep apnea-specific hypoxic burden - a metric predictive of OSA-associated risk - accurately using an oximetry signal provides clinicians with the ability to assess the riskiness of a patient’s OSA, either at baseline or following treatment, with minimal instrumentation. Additionally, the ability to estimate a patient’s OSA-associated risk using just an oximeter could allow for nightly data monitoring instead of single-night sleep tests, which can produce an inaccurate assessment of OSA severitydue to night-to-night variability and require instrumentation that can be cumbersome for patients.INCORPORATION BY REFERENCE

[0228] The contents of each of the following references is incorporated by reference herein in its entirety.1. Esmaeili N, Labarca G, Hu WH, et al. Hypoxic Burden Based on Automatically Identified Desaturations Is Associated with Adverse Health Outcomes. Ann Am Thorac Soc. 2023;20(ll):1633-1641. doi:10.1513 / AnnalsATS.202303-2480C2. Azarbarzin A, Sands SA, Stone KL, et al. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J. 2019;40(14): 1149-1157. doi : 10.1093 / eurheartj / ehy 6243. Topor ZL, Remmers JE, Grosse J, et al. Validation of a new unattended sleep apnea monitor using two methods for the identification of hypopneas. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2020;16(5):695-703. doi:10.5664 / jcsm.83244. Azarbarzin A, Sands SA, Taranto-Montemurro L, Vena D, Sofer T, Kim SW, Stone KL, White DP, Wellman A, Redline S. The Sleep Apnea-Specific Hypoxic Burden Predicts Incident Heart Failure. Chest. 2020 Aug;158(2):739-750. doi: 10.1016 / j.chest.2020.03.053. Epub 2020 Apr 13. PMID: 32298733; PMCID: PMC7417383.5. Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J. 2019 Apr 7;40(14): 1149-1157. doi: 10.1093 / eurheartj / ehy624. Erratum in: Eur Heart J. 2019 Apr 7;40(14):1157. doi: 10.1093 / eurheartj / ehz028. PMID: 30376054; PMCID: PMC6451769.

[0229] 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 ispertinent 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.

[0230] 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.

[0231] 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.

[0232] 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

AMENDED CLAIMSreceived by the International Bureau on 31 July 2026 (31.07.2026)1. A method comprising:obtaining a plurality of signals associated with a plurality of light waves respectively having different wavelengths over a period of time, wherein the plurality of signals are to be processed to estimate a blood oxygen level;obtaining a dot product value of two signal values of two signals among the plurality of signals at or around a time point in the period of time;comparing the dot product value to a threshold; andbased on the comparison of the dot product value to a threshold value, selectively including or excluding signal components in calculating a physiological parameter.

2. The method of claim 1, wherein the plurality of light waves are waves reflected from a skin surface.

3. The method of claim 1, wherein the plurality of signals is obtained based on data generated by a device comprising:a device body configured to couple to dentition; anda sensor device configured to couple to the device body.

4. The method of claim 3, wherein the sensor device comprises 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.

5. The method of claim 4, wherein the protruding portion is to press the tissue when the device body couples to the dentition.

6. The method of claim 4, wherein the protruding portion is to push the tissue when the device body couples to the dentition.

7. The method of claim 4, wherein the protruding portion comprises the sensor.

8. The method of claim 4, wherein the tissue comprises buccal mucosa.

9. The method of claim 4, wherein the tissue comprises a region of buccal mucosa closer to a maxillary arch than to a lip.

10. The method of claim 4, wherein the tissue comprises gingiva, palate, a lip, a tongue, retromolar trigone, tonsil, uvla, a floor of mouth, buccal mucosa around a lip, or a cheek.

11. The method of claim 4, wherein the sensor is configured to obtain information from the adjacent tissue when the device body couples to the dentition.

12. The method of claim 4, further comprising a receiving device configured to be operably linked to or connected to the sensor to receive the obtained information.

13. The method of claim 12, wherein the receiving device is disposed outside the oral cavity.

14. The method of claims 4-13, wherein the sensor is configured to be coupled to the device to sense through an outer surface of the device.

15. The method of claims 4-14, wherein the sensor device is configured to contact the tissue.

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