Smart Bioelectronic Spittoon for Real-Time Continuous Monitoring of Electrolytes in Saliva

Abstract

Exemplary embodiments of the present disclosure provide an apparatus for monitoring electrolytes in saliva. The apparatus may include a control circuit, a sensor coupled to the control circuit, and a biocompatible body configured to be inserted into a user's mouth. The biocompatible body may be configured to house the control circuit and the sensor, and the sensor may be configured to receive saliva from the user and measure the electrolyte level in the saliva.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the benefit of U.S. Provisional Application No. 63 / 337,328, filed May 2, 2022, which is hereby incorporated herein by reference in its entirety as if fully set forth below.

[0002] (Technical Field) Various embodiments of the present disclosure generally relate to medical diagnostic devices, and more particularly to non - invasive medical diagnostic devices for use in neonates.

Background Art

[0003] In the United States, more than 480,000 sick children, including neonates, receive intensive care every year. Infants admitted to neonatal intensive care units (NICUs) often require long - term hospitalization due to prematurity, low birth weight, or the need for special health management due to their health status. Continuous monitoring of important vital signs such as heart rate (HR), respiratory rate (RR), body temperature, blood oxygen saturation (SpO2), blood pressure, and blood ion levels is extremely important to prevent deterioration of health status and to efficiently allocate resources for patient care. For example, blood sodium levels (135 - 145 mM / L) are known to be related to blood pressure and heart failure, and blood potassium levels (3.6 - 5.2 mM / L) are known to be related to stroke. However, existing systems require a wall - mounted, bulky electronic processing unit that includes multiple wired electrodes and a sensor interface attached to the skin with an adhesive. Even worse, regular blood tests are required. As a result, these monitoring systems can potentially damage the vulnerable skin of patients and induce serious complications such as thrombosis, vascular occlusion, sepsis, rupture, bleeding, and death.

[0004] Electrolyte monitoring is very important for neonates and infants in intensive care units. However, the gold - standard method uses blood sampling, which is painful and does not allow continuous measurement.

[0005] Several studies have demonstrated a positive correlation between blood ion levels and saliva ion levels using optical detectors. However, these devices require rigid and bulky sensing components and additional support devices. For example, integrated circuits combined with either optical or electrochemical field-effect transistor systems have fragile parts made of silicon wafers that can lead to health-harmful results in continuous monitoring. Therefore, saliva-based detection is promising as an alternative, but existing devices are not effective for real-time continuous monitoring of electrolytes due to their rigidity, bulky form factors, and insufficient saliva accumulation. SUMMARY OF THE INVENTION

[0006] The present disclosure relates to a medical diagnostic device. Exemplary embodiments of the present disclosure provide an apparatus for monitoring electrolytes in saliva. The apparatus may include a control circuit, a sensor connected to the control circuit, and a biocompatible body configured to be inserted into a user's mouth. The biocompatible body may be configured to house the control circuit and the sensor, and the sensor may be configured to receive saliva from the user and measure the electrolyte level in the saliva.

[0007] In any of the embodiments disclosed herein, the biocompatible body may include a flow path having an inlet configured to receive saliva from the user, a reservoir in fluid communication with the inlet and configured to contain at least a portion of the saliva, and an outlet in fluid communication with the reservoir and configured to discharge saliva from the reservoir.

[0008] In any of the embodiments disclosed herein, the inlet may include a microfluidic flow path in fluid communication with the reservoir within which the sensor is disposed.

[0009] In any of the embodiments disclosed herein, the biocompatible body may form a mouthpiece, and the microfluidic flow path may be configured to pass saliva in one direction from the user's mouth to the reservoir.

[0010] In any of the embodiments disclosed in this specification, the microfluidic channel may include a base layer on which the microfluidic channel is formed and a top layer adhered to the base layer.

[0011] In any of the embodiments disclosed in this specification, the top layer may be adhered to the base layer by a medical-grade epoxy.

[0012] In any of the embodiments disclosed in this specification, the base layer and the top layer may include a hydrophilic material capable of drawing in the saliva.

[0013] In any of the embodiments disclosed in this specification, the hydrophilic material may include a poly(dimethylsiloxane)-poly(ethylene glycol) (PDMS-PEG) block copolymer (BCP).

[0014] In any of the embodiments disclosed in this specification, the depth of the microfluidic channel may be between about 350 and 650 micrometers.

[0015] In any of the embodiments disclosed in this specification, the sensor may include a first working electrode and a reference electrode.

[0016] In any of the embodiments disclosed in this specification, the sensor may further include a second working electrode.

[0017] In any of the embodiments disclosed in this specification, the first working electrode, the reference electrode, and the second working electrode may each include a wire-type electrode. The reservoir may include a plurality of rising members forming a capillary pattern configured to draw in the saliva that has passed through the first working electrode, the reference electrode, and the second working electrode.

[0018] In any of the embodiments disclosed herein, the first working electrode may be configured to detect sodium ions, and the second working electrode may be configured to detect potassium ions.

[0019] In any of the embodiments disclosed herein, the first working electrode may include a solid electrode, and the second working electrode may include a solid electrode.

[0020] In any of the embodiments disclosed herein, the first working electrode may further include a wire coated with a composite coating and a sodium-selective membrane. The second working electrode may further include a wire coated with a composite coating and a potassium-selective membrane.

[0021] In any of the embodiments disclosed herein, the control circuit may be configured to obtain data regarding sodium ions based on the potential difference between the first working electrode and the reference electrode from the sensor, obtain data regarding potassium ions based on the potential difference between the first working electrode and the reference electrode from the sensor, and transmit the data regarding sodium ions and the data regarding potassium ions to an end-user device.

[0022] Another exemplary embodiment of the present disclosure provides a method for manufacturing a mouthpiece for monitoring electrolytes in saliva. The method may include a step of forming a flow path, a step of fixing a sensor within the flow path, a step of operably coupling a control circuit to the sensor, and a step of fixing the flow path and the control circuit to the mouthpiece.

[0023] In any of the embodiments disclosed herein, the sensor may include a first working electrode and a reference electrode.

[0024] In any of the embodiments disclosed herein, the method may further include a step of fixing a second working electrode within the flow path and a step of operably coupling the control circuit to the second working electrode.

[0025] In any of the embodiments disclosed in this specification, the step of forming the flow path may include aligning the inlet of the flow path with the opening of the mouthpiece, forming, in the base layer of the material, a storage portion, a microfluidic flow path leading from the inlet to the storage portion, and an outlet, and bonding a top layer to the base layer with a medical-grade epoxy. The step of fixing the first working electrode may include placing the first working electrode in the storage portion before bonding the top layer to the base layer. The step of fixing the second working electrode may include placing the second working electrode in the storage portion before bonding the top layer to the base layer.

[0026] In any of the embodiments disclosed in this specification, the step of forming the flow path may further include disposing the medical-grade epoxy at an edge formed at a location where the top layer and the base layer are in contact so that the edge becomes hydrophilic.

[0027] In any of the embodiments disclosed in this specification, the material may include PDMS-PEG BCP.

[0028] In any of the embodiments disclosed in this specification, the method may further include the step of sterilizing the mouthpiece.

[0029] In any of the embodiments disclosed herein, the method may further include the step of fabricating the first working electrode, the step of fabricating the second working electrode, and the step of fabricating the reference electrode. The step of fabricating the first working electrode may include the step of cleaning a first wire, the step of coating the cleaned first wire with a composite coating, and the step of coating the first wire coated with the composite coating with a sodium-selective membrane. The step of fabricating the second working electrode may include the step of cleaning a second wire, the step of coating the cleaned second wire with the composite coating, and the step of coating the second wire coated with the composite coating with a potassium-selective membrane. The step of fabricating the reference electrode may include the step of cleaning a third wire, the step of coating the cleaned third wire with a resin, and the step of coating the third wire coated with the resin with a fluororesin copolymer.

[0030] In any of the embodiments disclosed herein, the composite coating may include carbon black suspended in silicone rubber.

[0031] Another exemplary embodiment of the present disclosure provides a method for determining a patient's electrolyte level. The method may include the step of placing an ion-sensing mouthpiece in the patient's mouth, the step of detecting the concentration of electrolytes in saliva, and the step of transmitting the concentration to the user.

[0032] In any of the embodiments disclosed herein, the step of detecting the concentration of the electrolyte may include the step of continuously drawing saliva from the patient's mouth through a microfluidic channel from an inlet of the ion-sensing mouthpiece into a reservoir, the step of obtaining a first signal from a first working electrode, and the step of comparing the first signal with a reference signal from a reference electrode. The first working electrode and the reference electrode may be disposed within a capillary pattern contained within the reservoir.

[0033] In any of the embodiments disclosed herein, the method may further include obtaining a second signal from a second working electrode and comparing the second signal with the reference signal from the reference electrode. The first working electrode and the reference electrode may be disposed within a capillary pattern included inside the reservoir.

[0034] In any of the embodiments disclosed herein, a first potential difference is obtained by comparing the first signal with the signal, and the method may further include converting the first potential difference into a concentration of a first electrolyte based on a calibration coefficient.

[0035] In any of the embodiments disclosed herein, a second potential difference is obtained by comparing the second signal with the reference signal, and the method may further include converting the second potential difference into a concentration of a second electrolyte based on the calibration coefficient.

[0036] In any of the embodiments disclosed herein, the first working electrode, the reference electrode, and the second working electrode may each include a wire-type electrode. The reservoir may include a plurality of rising members configured to draw in saliva that has passed through the first working electrode, the reference electrode, and the second working electrode.

[0037] In any of the embodiments disclosed herein, the first electrolyte may be sodium, and the second electrolyte may be potassium.

[0038] In any of the embodiments disclosed herein, the first working electrode may be a solid electrode, and the second working electrode may be a solid electrode.

[0039] In any of the embodiments disclosed herein, the first working electrode may further include a wire coated with a composite coating and a sodium-selective membrane. The second working electrode may further include a wire coated with a composite coating and a potassium-selective membrane.

[0040] These and other aspects of the present disclosure are described in the following "Detailed Description of the Invention" and the accompanying drawings. Other aspects and features of the embodiments will become apparent to those skilled in the art by considering the following description of specific exemplary embodiments in conjunction with the drawings. The features of the present disclosure may be described in connection with specific embodiments and drawings, but all embodiments of the present disclosure may include one or more of the features described herein. Further, although one or more embodiments may be described as having certain advantageous features, one or more of such features may also be used in conjunction with the various embodiments described herein. Similarly, although exemplary embodiments may be described below as embodiments of an apparatus, system, or method, it should be understood that such exemplary embodiments may be implemented in various apparatuses, systems, and methods of the present disclosure.

Brief Description of the Drawings

[0041] The following detailed description of specific embodiments of the present disclosure will be better understood when read in conjunction with the accompanying drawings. For the purpose of illustrating the present disclosure, specific embodiments are shown in the drawings. However, it should be understood that the present disclosure is not limited to the exact configuration and means of the embodiments shown in the drawings.

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[0056] Figure 7B is a detailed view of the flow channel of Figure 7A.

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[0072] Figure 14B is a detailed view of Figure 14A.

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DETAILED DESCRIPTION OF THE INVENTION

[0089] To facilitate an understanding of the principles and features of the present disclosure, various exemplary embodiments will be described below. The components, processes, and materials described below as constituting the various elements of the embodiments disclosed herein are intended to be illustrative and not limiting. Many suitable components, processes, and materials that will perform the same or similar functions as the components, processes, and materials described herein are intended to be included within the scope of the present disclosure. Such other components, processes, and materials not described herein include, but are not limited to, similar components or processes developed after the development of the embodiments disclosed herein.

[0090] As used herein, the term "microfluidic" is not intended to limit the flow channels and microchannels of the present disclosure to a specific size, and the microfluidic channels described herein can have many different sizes depending on the various embodiments of the present disclosure. In some embodiments, the depth of the microfluidic channel can be about 1000 microns or less. In some embodiments, the depth of the microfluidic channel can be about 500 microns or less. In some embodiments, the depth of the microfluidic channel can be between about 350 and 500 microns.

[0091] As shown in FIGS. 1A, 1B, and 2A, an exemplary embodiment of the present disclosure provides an apparatus 100 for monitoring electrolytes in saliva. The apparatus 100 can include a control circuit 110, a sensor 120 coupled to the control circuit 110, and a biocompatible body 130 configured to be inserted into the mouth 310 of a user 300. The biocompatible body 130 can be configured to house the control circuit 110 and the sensor 120, and the sensor 120 can be configured to receive saliva from the user 300 and measure the electrolyte level in the saliva.

[0092] In any of the embodiments disclosed herein, the biocompatible body 130 may include a flow path 132 having an inlet 134 configured to receive saliva from the user 300, a reservoir 136 in fluid communication with the inlet 134 and configured to contain at least a portion of the saliva, and an outlet 138 in fluid communication with the reservoir 136 and configured to discharge the saliva from the reservoir 136. The inlet 134 may include a microfluidic flow path 135 in fluid communication with the reservoir 136, and the sensor 120 is disposed within the reservoir 136. Figures 7A and 7B, Figures 8A and 8B, and Figures 15A and 15B show the flow path 132, the inlet 134, the reservoir 136, and the outlet 138 in more detail.

[0093] As shown in Figure 2B, the biocompatible body 130 may form a pacifier such as a commercially available pacifier, and the microfluidic flow path 135 may be configured to pass saliva unidirectionally from the user's mouth to the reservoir 136. In Figure 3, the device 100 is shown within the user 300's mouth, transmitting data to an end-user device.

[0094] As shown in Figures 7A and 7B, the microfluidic flow path 135 may include a base layer 135a in which the microfluidic flow path 135 is formed and a top layer 135b adhered to the base layer 135a. The top layer 135b may be adhered to the base layer 135a with a medical-grade epoxy. The base layer 135a and the top layer 135b may include a hydrophilic material capable of drawing in saliva. The hydrophilic material may include PDMS-PEG BCP.

[0095] In some embodiments, the depth of the microfluidic flow path 135 may be between about 350 and 650 micrometers.

[0096] As shown in Figure 13B, the sensor 120 may include a first working electrode 122 and a reference electrode 124. The sensor 120 may further include a second working electrode 126.

[0097] In any of the embodiments disclosed herein, the first working electrode 122, the reference electrode 124, and the second working electrode 126 may each include a wire-type electrode. The reservoir 136 may include a plurality of rising members 137 that form a capillary pattern configured to draw in saliva that has passed through the first working electrode 122, the reference electrode 124, and the second working electrode 126.

[0098] In any of the embodiments disclosed herein, the first working electrode 122 may be configured to detect sodium ions, and the second working electrode 126 may be configured to detect potassium ions.

[0099] In any of the embodiments disclosed herein, the first working electrode 122 may include a solid electrode, and the second working electrode 126 may include a solid electrode.

[0100] In any of the embodiments disclosed herein, the first working electrode 122 may further include a wire coated with a composite coating and a sodium-selective membrane. The second working electrode 126 may further include a wire coated with a composite coating and a potassium-selective membrane.

[0101] In any of the embodiments disclosed herein, the control circuit 110 may be configured to obtain data regarding sodium ions based on the potential difference between the first working electrode 122 and the reference electrode 124 from the sensor, obtain data regarding potassium ions based on the potential difference between the first working electrode 122 and the reference electrode 124 from the sensor, and transmit the data regarding sodium ions and the data regarding potassium ions to the end-user device.

[0102] As shown in FIG. 18A, the present disclosure provides a method 180 for manufacturing a saliva for monitoring electrolytes in saliva. The method 180 may include a step 182 of forming a flow path, a step 184 of fixing a sensor in the flow path, a step 186 of operably coupling a control circuit to the sensor, and a step 188 of fixing the flow path and the control circuit to the saliva.

[0103] In any of the embodiments disclosed in this specification, the sensor may include a first working electrode and a reference electrode.

[0104] As shown in FIG. 18B, method 180 may further include step 185 of fixing a second working electrode in the flow channel and step 190 of operably coupling the control circuit to the second working electrode.

[0105] As shown in FIG. 19A, step 182 of forming the flow channel may include step 182a of aligning the inlet of the flow channel with the opening of the mouthpiece, step 182b of forming a reservoir, a microfluidic channel communicating from the inlet to the reservoir, and an outlet in a base layer of the material, and step 182c of adhering a top layer to the base layer with a medical-grade epoxy. The step of fixing the first working electrode may include the step of placing the first working electrode in the reservoir before adhering the top layer to the base layer. Step 185 of fixing the second working electrode may include the step of placing the second working electrode in the reservoir before adhering the top layer to the base layer.

[0106] In any of the embodiments disclosed in this specification, step 182 of forming the flow channel may further include the step of disposing the medical-grade epoxy at an edge formed where the top layer and the base layer contact so that the edge becomes hydrophilic.

[0107] In any of the embodiments disclosed in this specification, the material may include PDMS-PEG BCP.

[0108] In any of the embodiments disclosed in this specification, method 180 may further include step 192 of sterilizing the mouthpiece.

[0109] As shown in FIG. 19B, method 180 may further include a step 194 of fabricating the first working electrode, a step 196 of fabricating the second working electrode, and a step 198 of fabricating the reference electrode. As shown in FIG. 20A, the step 194 of fabricating the first working electrode may include a step 194a of cleaning a first wire, a step 194b of coating the cleaned first wire with a composite coating, and a step 194c of coating the first wire coated with the composite coating with a sodium-selective membrane. As shown in FIG. 20B, the step 196 of fabricating the second working electrode may include a step 196a of cleaning a second wire, a step 196b of coating the cleaned second wire with a composite coating, and a step 196c of coating the second wire coated with the composite coating with a potassium-selective membrane. As shown in FIG. 20C, the step 198 of fabricating the reference electrode may include a step 198a of cleaning a third wire, a step 198b of coating the cleaned third wire with a resin, and a step 198c of coating the third wire coated with the resin with a fluoropolymer-copolymer.

[0110] In any of the embodiments disclosed herein, the composite coating may include carbon black suspended in silicone rubber.

[0111] FIG. 21A shows another exemplary embodiment of the present disclosure that provides a method 210 for determining a patient's electrolyte level. Method 210 may include a step 212 of placing an ion-sensing mouthpiece in the patient's mouth, a step 214 of detecting the concentration of electrolytes in saliva, and a step 216 of transmitting the concentration to the user.

[0112] In the embodiment shown in FIG. 21B, the step 214 of detecting the concentration of electrolytes may include a step 214a of continuously drawing saliva from the patient's mouth through a microfluidic channel from the inlet of the ion-sensing mouthpiece into a reservoir, a step 214b of obtaining a first signal from a first working electrode, and a step 214c of comparing the first signal with a reference signal from a reference electrode. The first working electrode and the reference electrode may be disposed within a capillary pattern contained within the reservoir.

[0113] In any of the embodiments disclosed herein, the method may further include step 218 of obtaining a second signal from a second working electrode, and step 220 of comparing the second signal with a reference signal from a reference electrode. The first working electrode and the reference electrode may be disposed within a capillary pattern included inside the reservoir.

[0114] In any of the embodiments disclosed herein, a first potential difference is obtained by the step of comparing the first signal with the reference signal, and method 210 may further include step 222 of converting the first potential difference into the concentration of a first electrolyte based on a calibration coefficient.

[0115] In any of the embodiments disclosed herein, a second potential difference is obtained by step 220 of comparing the second signal with the reference signal, and method 210 may further include step 224 of converting the second potential difference into the concentration of a second electrolyte based on a calibration coefficient.

[0116] In any of the embodiments disclosed herein, the first working electrode, the reference electrode, and the second working electrode may each include a wire-type electrode. The reservoir may include a plurality of rising members that form a capillary pattern configured to draw in saliva that has passed through the first working electrode, the reference electrode, and the second working electrode.

[0117] In any of the embodiments disclosed herein, the first electrolyte may be sodium, and the second electrolyte may be potassium.

[0118] In any of the embodiments disclosed herein, the first working electrode may be a solid electrode, and the second working electrode may be a solid electrode.

[0119] In any of the embodiments disclosed herein, the first working electrode may further include a wire coated with a composite coating and a sodium-selective membrane. The second working electrode may further include a wire coated with a composite coating and a potassium-selective membrane.

[0120] The following examples further illustrate aspects of the present disclosure. However, these do not in any way limit the teachings or disclosure of the present disclosure described herein.

Example

[0121] Disclosed herein is an example of a smart wireless baby pacifier for monitoring electrolytes in a newborn's saliva, which can continuously detect sodium and potassium levels in real time without blood sampling. This small system facilitates seamless integration of an ultra-lightweight and thin device into a commercially available pacifier without additional fixtures or structural changes. This portable device includes an ion-selective sensor, a flexible circuit, and a microfluidic channel, enabling a simplified measurement protocol for non-invasive electrolyte monitoring. The flexible microfluidic channel enables continuous and efficient saliva collection from the mouth. By changing the surface properties of the channel and the structure of the capillary reservoir, the device described herein achieves reliable pumping of viscous media for rapid calibration and measurement. The sensors in the system exhibit good stability and sensitivity, with the sodium sensor showing 52 mV / decade and the potassium sensor showing 57 mV / decade. In an in vivo study of newborns in the intensive care unit, the feasibility and performance of the device in detecting important saliva-based electrolytes without stimulation have been demonstrated.

[0122] To address the problems of modern sensor systems, miniaturized potentiometric solid-state ion-selective electrodes (SS-ISEs) have been adopted as a good solution. Advanced SS-ISEs have successfully replaced the fragile components of conventional electrodes, enabling the miniaturization of sensors. However, general SS-ISEs exhibit an inherent instability when subjected to repeated drying and stretching. Also, film-type ion sensors require a relatively large surface area in contact with the analyte to obtain reliable signals. Especially in the case of newborns in the NICU, since infants cannot express discomfort or illness, accuracy is of utmost importance to medical professionals and caregivers.

[0123] In recent years, wearable physiological monitors and glucose detectors for infants have been developed, but ion detection still relies on blood measurements. More importantly, in studies using SS-ISEs, the correlation between blood ions and saliva ions is often overlooked, raising questions about the validity of continuous and non-invasive monitoring. In saliva monitoring, ion levels depend on the sampling method, the target sampling site (i.e., gland), and environmental conditions. To obtain consistent results, it is essential to standardize the method of supplying fresh saliva to the ion sensor surface.

[0124] The devices disclosed herein may comprise needle-type sensors that fit in a much narrower space than film-type sensors, such as in a microfluidic flow channel structure. This small ion sensor made of thin metal wires can be embedded in the small inner wall of a commercially available pacifier. The entire system is flexible with a small form factor and can be seamlessly attached to the pacifier without additional support parts or structural changes. The microfluidic flow channel continuously aspirates saliva from the subject's mouth, enabling real-time monitoring of electrolytes. A specific pattern within the flow channel maximizes capillary action against viscous saliva and securely fixes the sensitive ion sensor within the flow channel reservoir. Further, the microfluidic flow channel maintains hydrophilicity for at least 7 days after oxygen plasma treatment by adding poly(dimethylsiloxane)-poly(ethylene glycol) (PDMS-PEG). This bioelectronic system utilizes a low-energy Bluetooth module suitable for long-term continuous monitoring of target ions. In in vivo studies targeting infants, the performance of this device in continuous monitoring of saliva electrolytes from unstimulated saliva has been demonstrated. This device can provide evidence for non-invasive, wireless, continuous, real-time, and easily evaluable infant saliva diagnostics.

[0125] To verify the flow behavior when the microfluidic channel sucks saliva, fluid simulations were performed using ANSYS FLUENT. Regarding the fluid properties, considering the reported saliva viscosities (male: average 1.05, SD 0.42, female: average 1.29, SD 0.70), the viscosity was assumed to be 2 cP. Since 99% of the saliva composition is water, the density of saliva was assumed to be the same as that of water. The surface tension of saliva is 58 mM / N. From these data and assumptions, it was shown that the Reynolds number (Re) was much smaller than 1 in all channel regions. This means that the flow in the microfluidic channel is laminar throughout the device and the viscous effect is dominant. Also, the Weber number (We) was much smaller than 1. This means that the surface tension was stronger than the inertial force. The capillary number (Ca) indicated that the surface force was stronger than the viscous force. In short, the physics of fluid flow in the microfluidic channel was dominated by viscous and capillary effects.

[0126] Therefore, the pressure loss in the channel can be expressed as in Equation 1 below.

[0127] Equation 1

[0128]

Number

[0129] Equation 2 represents the capillary pressure.

[0130] Equation 2

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Number

[0132] According to Equation 1 and Equation 2, the cross-section of the microfluidic channel decreases as the pressure loss increases. To avoid high pressure loss, it is necessary to make the channel width larger than 100 μm. Since Re was calculated to be less than 1, the simulation was performed under laminar flow conditions. The shape was the same as the final microfluidic channel design. The flow velocity was set to the inlet flow velocity (0.0228 mm / s), and the outlet condition was zero gauge pressure. Based on this microfluidic channel test, the total elapsed time was 25 minutes. The inlet flow velocity can be calculated using the volume of the flow channel chamber and the total elapsed time.

[0133] Regarding the materials and methods used in these examples, they are as follows. This device may include a Bluetooth built-in circuit and a microfluidic channel integrated with sensors. Examples of the ion sensor of this system include, for example, a metal conductor covered with an appropriate polymer film, all of which are seamlessly integrated into the nipple of an infant.

[0134] The general materials used in the device are as follows. Sodium tetrakis-[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB) was purchased from Alfa Aesar. 4-tert-Butylcalix[4]arene-tetraacetic acid tetraethyl ester (sodium ionophore X), bis(2-ethylhexyl) sebacate (DOS), polyvinyl chloride (PVC), tetrahydrofuran (THF), potassium tetrakis(p-chlorophenyl)borate (KTClPB), hydrochloric acid (HCl), Ag wire, Nafion, trichloro(1H,1H,2H,2H-perfluorooctyl)silane, and polyvinyl butyral (PVB) were purchased from Sigma Aldrich. Sodium chloride, potassium chloride, calcium chloride dihydrate, and magnesium chloride hexahydrate were obtained from Fisher Chemical. Ecoflex 00-30 was purchased from Smooth-On, and carbon black (CB, Vulcan XC 72R) (CB) was obtained from Fuel Cell Store. PDMS-PEG BCP (DBE-712) was purchased from Gelest. The medical grade epoxy adhesive was purchased from Epoxy International.

[0135] Three ion electrodes were integrated into a flexible circuit. This circuit may include a Bluetooth low energy chip, a 2.45 GHz chip antenna, and a rechargeable battery 139. The flexible circuit can be used to detect the potential difference between the working electrode and the reference electrode. The measurement data can be wirelessly transmitted to a monitoring device such as a tablet or smartphone.

[0136] Figure 16 shows the fabrication and measurement setup of the electrodes. To fabricate the electrodes, silver wires are ultrasonically treated in an IPA bath for 30 minutes. After the cleaning procedure, the wires are cut to 3 cm. The CB / Ecoflex composite was prepared by mixing 6 wt% CB and 94% Ecoflex 00-30 in 15 g of toluene and stirring at 600 rpm for 30 minutes. After mixing, the pre-cleaned Ag wires are dip-coated with the composite paste. Then, the CB / Ecoflex composite transducer is cured at 150 °C overnight. For the reference electrode, the Ag wire is chlorinated at 1 mA / cm 2 in 0.1 M KCl and 0.01 M HCl solution for 1 minute. 2.5. After complete drying, the CB / Ecoflex electrodes are coated with a sodium ion-selective membrane (ISM) or a potassium ion-selective membrane (ISM). The following two types of ISMs were used. 1) Sodium ISM: In 2 mL of THF, sodium ionophore X (2.67 mg), DOS (174.53 mg), PVC (88 mg), NaTFPB (1.47 mg), and 2) Potassium ISM: In 2 mL of THF, KTFPB (0.8 mg), valinomycin (2 mg), PVC (65.8 mg), DOS (131.4 mg). These mixtures are vortexed for 6 hours to make a homogeneous solution. The Ag / AgCl RE was coated with a membrane cocktail consisting of 78.1 mg of PVB, 50 mg of KCl, and 1 mL of methanol. The resulting ISE and RE were dried at room temperature overnight.

[0137] To evaluate the characteristics of the electrode sensitivity, sensor information was obtained using sodium chloride solutions with different concentrations. Considering the normal ion levels in human saliva (sodium: 4 - 37 mM, potassium: 2.6 - 18.3 mM), 10 -3A solution of ~0.1 M was used. To test for long-term reproducibility and selectivity, an overnight conditioning was performed, after which measurements were started (when the sensor was completely dry), and repeated measurements were made to remove residues on the sensor surface and washed at least three times. Voltage responses of all-solid-state ion ISEs and commercially available RE (NT_MRX11) were performed. All sensor measurements were carried out using a Gamry potentiostat (Interface 1010E, Gamry Instruments Inc).

[0138] Figure 12 shows an example of the manufacturing process of a microfluidic channel mold. To fabricate a microfluidic channel, PDMS-PEG is used as an additive in the hydrophilic modification of the microfluidic channel. PDMS-PEG BCP is added to the PDMS base and mixed with a curing agent to a concentration of 1.0% (w / w). The mixture (PDMS + PDMS-PEG) is blended, poured onto a silicon wafer, and molded into a microfluidic channel. Trapped air bubbles are removed in a low-pressure desiccator. Prior to the molding process, it is necessary to sufficiently treat (salinize) the silicon wafer mold with salt to improve the clean demolding process. This process is carried out by incubating 2 μL of trichlorosilane (Sigma-Aldrich) droplets with the silicon wafer in a low-pressure desiccator overnight. Subsequently, the prepared PDMS-PEG is poured onto the wafer and cured in an oven at 70 °C for 24 hours. Finally, the microfluidic channel structure is removed from the mold and adhered to a thin PDMS-PEG slab.

[0139] Figures 13A to 14 show an example of the integration procedure of a smart pacifier. Figure 13A shows the state of pin-coating an epoxy adhesive on a slide glass, pressing the channel structure, and placing it on a slide glass spin-coated with PDMS-PEG. Figure 13B shows the state of embedding an ion sensor in the channel. After integration, the gap between the channel and the electrode is filled with an epoxy adhesive. Figure 14 shows the state of attaching the integrated channel structure to the inner wall of the pacifier with a medical-grade epoxy adhesive. While connecting the electrode to a wireless circuit, the wireless circuit was attached to the pacifier with a normal epoxy adhesive.

[0140] To integrate the components of the device, each prepared ion sensor is embedded in the microfluidic channel. The gap between the ion sensor and the channel is sealed with a medical-grade epoxy adhesive and cured at room temperature for 24 hours. A commercially available pacifier sterilized with ethylene oxide (EO) gas is attached to the flexible circuit using a medical-grade epoxy adhesive to ensure biosafety. After curing the epoxy, the microfluidic channel is integrated with the ion sensor on the inner wall of the pacifier and connected to the circuit pads by soldering. Figure 15A shows a cross-sectional view of the integrated channel inside the sterilized pacifier. The infant holds only the pacifier and the biocompatible inlet, and the hydrophilic channel and the capillary reservoir continuously absorb the saliva sample. Figure 15B shows the capillary reservoir and the ion sensor inside the microfluidic channel.

[0141] Regarding the surface property evaluation of PDMS-PEG BCP, it is as follows. The water droplet contact angle in the polymer sample was measured. The wettability performance of the PDMS-PEG BCP additive was obtained using a contact angle goniometer (Ossila). 6 μL of DI water was placed on a slide glass spin-coated with PDMS + PDMS-PEG BCP, and the contact angle was measured at 5-minute intervals to obtain time-series data of the surface arrangement. Quantitative data was plotted as mean ± standard deviation (n = 3) when shown.

[0142] The inventor conducted a clinical study to evaluate the potential of the above smart pacifier example as a wearable non-invasive platform for continuously and real-time monitoring of ions in saliva in vivo. As shown in FIG. 1A, this device may comprise a pacifier, a flexible wireless circuit, a small microfluidic channel in which an ion sensor is embedded, and a rechargeable battery. The flexible circuit can be seamlessly attached to the back side of the pacifier. Another example of the pacifier is shown in FIGS. 1B - 2B. Specifically, the saliva of an infant is sucked into the end of the channel exposed on the back of the pacifier to make the microfluidic channel flow continuously. As soon as the pacifier is inserted into the lips, saliva is sucked through the channel. Thereafter, fresh saliva is continuously and automatically supplied to the reservoir containing the ion sensor. FIGS. 7A, 7B, 12, 13A, 13B, 14, and 16 show the detailed manufacturing process of the device examples disclosed herein. Generally, the assembly of the device is performed in multiple steps, including the fabrication of the flexible circuit, the ion sensor, and the microfluidic channel, the integration of the sensor into the microfluidic structure, the attachment of the channel with the embedded sensor and the circuit to the pacifier surface, and the final connection of the sensor and the rechargeable battery to the circuit pads by soldering. A rechargeable battery with a magnetic connector can be used. The flowchart of FIG. 4A shows an example of a method for continuously and wirelessly monitoring ions, juxtaposed with an example of a discrete sampling method. The voltage difference between the reference electrode (RE) and the two SS-ISEs is measured and recorded by a mobile device with data filtering implemented to suppress the random noise signal.

[0143] Figures 7A and 7B show the layer-by-layer structure of an example of an embedded microfluidic channel. The channel comprises a PDMS-PEG layer, an ion sensor, a capillary reservoir, and a PDMS-PEG base layer. The reservoir consists of capillary patterns grouped in multiple rows to fill the gaps between the sensors. The design of the top layer is all at a depth of 500 μm. One of the important advantages of the device disclosed herein is the continuous transport of saliva, which eliminates the need for conventional discrete manual sampling. Although numerous studies have been conducted on PDMS channels, there are significant challenges in the analysis of infant saliva in this study. Saliva is much more viscous than other biological fluids such as sweat. The microfluidic channel needs to be able to transport saliva in a vertical position. This position is one in which gravity acts directly against the capillary effect. The surface of the ion sensor needs to remain wet during monitoring. Also, PDMS is essentially a hydrophobic material that hinders the capillary effect. To address these challenges, the inventors are using PDMS-PEG and capillary pattern design in these examples.

[0144] The PDMS surface exposed to oxygen plasma becomes hydrophilic, and it is well known that when three or four oxygen atoms are bonded to silicon atoms, the hydrophobicity decreases. The main drawback of this method is the hydrophobic recovery of PDMS. When PDMS-PEG BCP (1% w / w) is added during the mixing of the PDMS base and curing agent, PDMS-PEG BCP modified PDMS (PDMS + PDMS-PEG BCP) is obtained. The PDMS-PEG BCP additive self-organizes at the PDMS interface and forms a hydrophilic PEG layer when exposed to water. The inventors measured the sessile drop water contact angles (WCA) of water by the droplet method to test the hydrophilicity over time. The graph in Figure 11A shows the difference in the initial contact angles of PDMS and PDMS-PEG BCP after oxygen plasma treatment. The WCA of PDMS exceeded 100°, while the WCA of PDMS-PEG BCP remained less than 80° even after 7 days. Furthermore, when in contact with water, the surface becomes hydrophilic due to the rearrangement of the PEG groups. Figure 11B shows the decrease in the contact angle over time. When PDMS-PEG BCP was exposed to water, the WCA decreased significantly over time. Samples with a higher BCP content (1.5% and 2.0% PDMS-PEG BCP) showed higher hydrophilicity. However, the higher the proportion of BCP, the significantly higher the viscosity of the sample before curing. The viscosity was too high to remove the trapped air bubbles from the sample after the molding process.

[0145] Table 1 shows the measurement results of the water contact angle (WCA) of the PDMS-PEG surface.

[0146]

Table 1A

Table 1B

Table 1C

[0147] Epoxy adhesives are hydrophilic due to polar epoxy groups. For bonding microfluidic channels, medical-grade epoxy adhesives can be used. To apply the epoxy adhesive to the microfluidic channel, a stamping method can be used. After placing a slab on the microfluidic channel, the epoxy adhesive is pushed into the microchannel chamber. Then, the gap between the slab and the channel is filled to make the edge where the channel and the slab chamber contact hydrophilic. The function of the capillary pattern is to enhance capillary force and prevent the collapse of the reservoir chamber. Next, a commercially available pacifier is sterilized using EO gas so as not to harm the infant who is the subject. Then, the channel with the sensor embedded and the flexible circuit are integrated into the sterilized pacifier. By doing so, only the safe parts to which the subject is exposed, that is, only the sterilized pacifier and the biocompatible PDMS inlet, are left. Furthermore, the outlet of the 2-cm-long channel is arranged on the back side of the device as shown in FIG. 15A, and the used saliva hardly reaches the subject and has little impact after measurement. Due to the ability of the channel to suck in fluid, as shown in FIG. 15A, saliva can pass through in one direction without backflow. Finally, the device examples disclosed in this specification minimize the toxicity problems related to sensors, circuits, or batteries through these processes. Also, the fluid transport ability of the microchannel in FIG. 15B has been demonstrated by simulation results and experimental verification. The channel has successfully transported saliva vertically even without an ion sensor. After the sensor is integrated into the microfluidic channel, the gap between the capillary pattern groups in the reservoir is filled by the ion sensor.

[0148] Figures 5A and 5B and Figures 6A - 6C summarize the performance and characteristic evaluation data of the sensor. A thin wire - type ion sensor consisting of a working electrode (WE) and a reference electrode (RE) can be seamlessly embedded in the prepared microfluidic channel. The detailed fabrication procedure and measurement setup of the ion sensor are shown in Figure 16. Each WE, where the ion - electron transducer is a composite of CB and Ecoflex, was coated with a sodium - ion - selective membrane and a potassium - ion - selective membrane. Another silver - wire sample was electrochemically chlorinated to coat a chemically stable surface of silver chloride. Then, by applying PVB / KCl and Nafion, the dissolution of chloride ions was prevented, thereby avoiding signal malfunctions. The inventors confirmed the functionality of the wire - type sensor. To verify the functionality of the ion - selective electrode, a bench - top potentiometer was used in comparison with the measurement values of the wireless system shown in Figures 17B and 17D and Table 2 below. The real - time voltage transient phenomena measured by the potentiometer are shown in Figures 10A and 10D. The sodium - sensing electrode and the potassium - sensing electrode were 10 -3 M, 10 -2 M, and 10 -1It shows a stable and reproducible rapid response to M NaCl and KCl solutions, demonstrating the good functionality of these wire-type sensors. The calculated sensitivities (52 mV / decade for the sodium ion sensor and 57 mV / decade for the potassium ion sensor) confirm that the electrode responses are close to the theoretical values according to the Nernst equation shown in FIGS. 17B and 17D. The inventors also observed similar results when the other end of the silver wire was soldered to a smart mouthpiece circuit designed to perform measurements and data transfer wirelessly. The voltage stability of the sensor is very important for clinical applications, and the low accuracy of the SS-ISE due to unwanted signal fluctuations is a problem. The inventors solved this stability problem in this study, as demonstrated in FIGS. 10C and 10F. Each electrode showed long-term stability of 4.3 mV / h in NaCl solution and 3 mV / h in KCl solution over 10 hours. The inserted images in FIGS. 10C and 10F show enlarged views of the voltage fluctuations over 1 hour, and the standard deviations are 2.0 mV and 0.3 mV for each ion, respectively. The demonstrated stability of the sensor is notable considering that the device is designed to operate for several hours. Furthermore, these results confirmed the effectiveness of the electrode structure that particularly focuses on a small wire-like form that can be easily and seamlessly integrated into a miniaturized fluid flow path.

[0149] Table 2 shows the results of the detection characteristics measured using a desktop device and the wireless device disclosed in this specification.

[0150]

Table 2

[0151] An example of a medical implementation of the smart pacifier is shown in FIG. 4B. FIG. 4B demonstrates the performance of the device by comparing the data with conventional blood sampling results. For this in vivo study, a commercially available pacifier integrated with sensors and electronic circuits as shown in FIG. 3 was used. The inventor integrated a flexible circuit, sensors, and microfluidic channels with minimal design changes after sterilizing the pacifier. During this study, only pre-cleaned areas came into contact with the subjects inside the mouth. In the wearable design of the pacifier, using a common pacifier provides comfort to the subject (infant) while reducing manufacturing costs. FIG. 4B shows a comparison between non-invasive measurement of ion concentration in saliva (smart pacifier) and invasive measurement of ion concentration in serum (blood sampling). The examples of pacifiers disclosed herein continuously monitor sodium and potassium ions in saliva in real time for several hours. Currently, electrolyte-based health monitoring in the NICU requires blood sampling from the infant's foot at least twice a day, usually with a heel prick. More importantly, blood sampling is a discrete measurement at a single point that cannot provide real-time health information for sick infants. Although there are many types of ion sensors that show great potential for higher accuracy and multimodal analysis, due to their bulky structures, they are limited to using only the excreted saliva. Such systems are insufficient to meet the need for continuous sampling and analysis, especially in the case of infants who cannot collect samples by themselves. Furthermore, the resulting electrolyte levels depend greatly on measurement settings such as the sampling site, method, and temperature. These parameters may be ignored in discrete sampling methods. For example, the sodium ion concentration in saliva varies from 5.6 mM to 70 mM, which limits the clinical use of saliva diagnosis.

[0152] A series of data from FIGS. 5A - 6C demonstrate the unique advantages of the smart pacifier system in the detection of sodium and potassium ions. Each sensor was calibrated after being adjusted using three types of calibration solutions. The inventor shortened the calibration time by using a cotton swab and a blower to suck up the solution remaining in the flow path. As shown in FIG. 2C, 10 -3, and 10 -2 , and 10 -1 The system is calibrated using small droplets (less than 5 mL) of NaCl solution and KCl solution. By tilting the small container at approximately 45 degrees, a clear signal due to the hydrophilic surface of the microfluidic channel could be captured. Also, as shown in FIGS. 5A and 5B, the inventors increased the gain of the voltage signal to improve the measurement accuracy. Using the amplifier circuit gain, the user-adjustable circuit gain is multiplied by the voltage value and sensitivity via a mobile app. In this case, when the gain was set to 1.5, the linearities of the sodium ion sensor and potassium ion sensor were 80 mV / decade and 95 mV / decade, respectively. The sensitivities of these sensors were calculated to be 53 mV / decade and 63 mV / decade, which are close to the Nernst level (59 mV / decade). This difference may result from differences in temperature, voltage stability of the reference electrode, and biological adhesion on the sensor surface. FIG. 6A verifies the performance of the wearable device in continuous monitoring of sodium and potassium in saliva. The measurement data shows that the sodium concentration in saliva was 5.7 - 9.1 mM (average value: 7.1 mM) and the potassium concentration was 4.2 - 5.2 mM (average value: 4.6 mM). It should be noted that the low ion levels detected in the first 30 minutes may be due to the pumping effect, as it can take up to 25 minutes for the viscous fluid to reach the sensor. The ratio of sodium level to potassium level is well known to be related to various health problems such as cardiovascular disease, chronic kidney disease, diabetes, and aldosteronism. As shown in FIG. 6C, the smart mouthguard measures the sodium-to-potassium ratio and can be used for disease diagnosis and prognosis prediction.

[0153] In summary, these examples provide insights into important areas of non-invasive saliva monitoring. This approach creates an all-in-one function that addresses the challenge of developing a fully automated non-invasive protocol. Also, there is no need to collect saliva samples (which may require medical staff if the patient is an infant) and discretely drop the samples onto the thin-film electrodes. This wearable device is designed to simultaneously perform continuous sampling, automatic measurement, and real-time data streaming to maximize user comfort and practical efficiency. To verify the accuracy of the wearable device, a correlation with blood ions under discrete sampling conditions in the clinical setting was established: y = 1.25x + 120.7, where x is the sodium level in saliva and y is the sodium level in blood. Using this equation, the blood sodium concentration was calculated to be 130 mM on average, lower than the saliva measurements (139 mM and 138 mM). This slight discrepancy can be explained by the difference between discrete blood sampling and continuous saliva detection, which may be affected by temperature, sampling procedure, and gland site. For example, the well-known Nernst equation shows that temperature has a significant impact on the resulting potential value. Therefore, in clinical trials (such as urinary catheters), the use of a temperature sensor is recommended to correct for the body temperature difference between the bladder temperature and the equilibration temperature used to prepare the standard substance. Temperature is an important factor.

[0154] The present disclosure relates to a portable bioelectronic saliva system that enables wireless, real-time, and continuous detection of sodium and potassium levels without blood sampling. This miniaturized wearable system demonstrated reliable electrolyte monitoring in neonatal saliva for the first time. In in vivo studies in the NICU, it was demonstrated that this device could continuously monitor sodium levels (5.7 - 9.1 mM) and potassium levels (4.2 - 5.2 mM) in real time. A flexible platform comprising a wireless circuit, a surface-modified microfluidic channel, and an SS-ISE embedded in a capillary reservoir was able to provide non-invasive neonatal health monitoring along with saliva.

[0155] Figure 9 is a diagram capturing the main detection components of the smart pacifier for wireless data recording by a portable device. Figure 4A shows a comparison between the measurement protocol of the all-in-one ion monitor disclosed in this specification and an existing desktop device.

[0156] Figure 11A is a plot showing the time-dependent comparison of the contact angle of water on PDMS and on PDMS-PEG. Figure 11D is a plot showing the change in the contact angle of water on PDMS-PEG over time. Each inserted image shows a photograph of the contact angle at the 0-minute, 25-minute, and 45-minute time points on the surface. Figure 8A shows the simulation results of the time-dependent fluid transport until the flow channel is filled. Figure 8B shows the experimental verification of the transport performance of the microfluidic flow channel, showing a similar trend as estimated in Figure 8A.

[0157] Figures 10A to 10F relate to the characterization of the ion sensor. Figures 10A and 10B show the time-voltage transient phenomena measured at different NaCl solution concentrations (10-3 M, 10-2 M, and 10-1 M) and the sensitivity of the sodium ion sensor. Figure 10C shows the results of a 10-hour voltage stability test of the sodium ion sensor, together with an enlarged inserted view of 1-hour data. Figure 10D shows the voltage signals recorded in 10-3 M, 10-2 M, and 10-1 M KCl solutions. Figure 10E shows the calculated sensitivity of the potassium sensor. Figure 10F shows a 10-hour long-term stability test of the sensor (inserted view: 1-hour voltage transient phenomenon).

[0158] Figures 17A to 17D show the voltage signals measured from the wireless circuit and the comparison of their sensitivity with the theoretical (Nernst) values. Figures 17A and 17B show the voltage signals of the sodium ion sensor in 10-3, 10-2, 10-1 NaCl solutions. Figures 17C and 17D show the voltage signals of the sodium ion sensor in 10-3, 10-2, and 10-1 KCl solutions. The highlighted square regions indicate the known values of sodium and potassium levels in saliva.

[0159] Figure 5A shows the calibration results of sensors using sodium ions with different concentrations. Figure 5B shows the calibration results of sensors for detecting potassium ions. Figures 6A and 6B show the sodium ion levels and potassium ion levels recorded simultaneously over a period of one hour, demonstrating real-time continuous monitoring. Figure 6C shows the sodium-to-potassium ion ratio useful for prognosis prediction and diagnosis of diseases such as cardiovascular disease risk.

[0160] It should be understood that the embodiments and claims disclosed herein are not limited in their application to the details of the structure and arrangement of the components described herein and shown in the drawings. Rather, this specification and the drawings provide examples of the contemplated embodiments. The embodiments and claims disclosed herein are further capable of other embodiments and can be practiced and carried out in various ways. Also, it should be understood that the expressions and terms employed herein are for purposes of description and should not be regarded as limiting the claims.

[0161] Thus, those skilled in the art will understand that the concepts underlying this application and the claims can be readily utilized as a basis for the design of other structures, methods, and systems for carrying out some of the purposes of the embodiments and claims presented in this application. Thus, it is important that the claims be regarded as including such equivalent constructions.

[0162] Furthermore, the purpose of the "Abstract" is to enable the general public, including the United States Patent and Trademark Office and those skilled in the art who are not particularly familiar with patent and legal terms and expressions, to quickly grasp the content and gist of the technical disclosure of this application by just a cursory reading. The "Abstract" does not define the claims of this application and does not limit the claims in any way.

Claims

1. A sensor and, It is inserted into the user's mouth, The system receives saliva from the user and guides the saliva through a channel to communicate with the sensor. It is configured to include a biocompatible body, The sensor is configured to measure the electrolyte level in the saliva. An apparatus wherein at least a portion of the channel includes a hydrophilic material configured to draw the saliva into the channel.

2. The flow path comprises a storage section in which the sensor is located, The hydrophilic material includes poly(dimethylsiloxane)-poly(ethylene glycol) (PDMS-PEG), The sensor comprises a first working electrode, a second working electrode, and a reference electrode, and the storage portion comprises a rising member that forms a capillary pattern configured to draw in saliva passing through the first working electrode, the reference electrode, and the second working electrode. The apparatus according to claim 1, wherein at least one of the following is the apparatus.

3. The flow path is An inlet equipped with a microfluidic channel, A reservoir configured to have fluid flow through the microfluidic channel and to contain at least a portion of the saliva and the sensor, An outlet is configured to communicate with the aforementioned storage section and discharge saliva from the storage section, Equipped with, The apparatus according to claim 1, wherein the microfluidic channel is configured to allow saliva to pass in one direction from the user's mouth to the storage section.

4. Further comprising a control circuit, The sensor is coupled to the control circuit. The apparatus according to claim 1, wherein the biocompatible body is further configured to house the control circuit and the sensor.

5. The aforementioned flow path The base layer on which the microfluidic channels are formed, The top layer is bonded to the base layer, The apparatus according to claim 4, comprising:

6. The apparatus according to claim 5, wherein the top layer is bonded to the base layer with medical-grade epoxy.

7. The apparatus according to claim 5, wherein the base layer and the top layer include the hydrophilic material.

8. The apparatus according to claim 7, wherein the hydrophilic material includes PDMS-PEG.

9. The aforementioned sensor, The first working electrode and Reference electrode and, The second working electrode and Equipped with, The apparatus according to claim 7, wherein the storage section comprises a rising member that forms a capillary pattern configured to draw in saliva passing through the first working electrode, the reference electrode, and the second working electrode.

10. The sensor is A first working electrode configured to detect sodium ions, A second working electrode configured to detect potassium ions, The apparatus according to claim 7, comprising:

11. The sensor is A first working electrode including a solid electrode, A second working electrode including a solid electrode, The apparatus according to claim 7, comprising:

12. The sensor is A first working electrode comprising a wire coated with a composite coating and a sodium-selective film, A second working electrode comprising a wire coated with a composite coating and a potassium-selective film, The apparatus according to claim 7, comprising:

13. The sensor further comprises a reference electrode, The control circuit, From the sensor, data relating to the sodium ions based on the potential difference between the first working electrode and the reference electrode is obtained. From the sensor, data relating to the potassium ions based on the potential difference between the second working electrode and the reference electrode is obtained. The data relating to sodium ions and the data relating to potassium ions are transmitted to the end-user device. The apparatus according to claim 10, configured as described above.

14. A device for monitoring electrolytes in saliva, Control circuit and A sensor coupled to the control circuit, A biocompatible body configured to be inserted into the user's mouth and to house the control circuit and the sensor, Equipped with, The biocompatible body is equipped with a flow channel, The aforementioned flow path An entrance configured to receive saliva from the user, A storage section is configured to communicate with the inlet and contain at least a portion of the saliva, An outlet is configured to communicate with the aforementioned storage section and discharge saliva from the storage section, Equipped with, The inlet is equipped with a microfluidic channel that is in fluid communication with the reservoir in which the sensor is located. The sensor is configured to receive saliva from the user and measure the electrolyte level in the saliva. The aforementioned microfluidic channel The base layer on which the microfluidic channels are formed, The top layer is bonded to the base layer, Equipped with, An apparatus wherein the base layer and the top layer include a hydrophilic material capable of attracting the saliva.

15. The biocompatible body includes a pacifier, The apparatus according to claim 14, wherein the microfluidic channel is configured to allow saliva to pass in one direction from the user's mouth to the storage section.

16. The apparatus according to claim 14, wherein the top layer is bonded to the base layer with medical-grade epoxy.

17. The apparatus according to claim 14, wherein the hydrophilic material comprises poly(dimethylsiloxane)-poly(ethylene glycol).

18. The sensor is The first working electrode and Reference electrode and, It is equipped with a second working electrode, The apparatus according to claim 14, wherein the storage section comprises a plurality of rising members that form a capillary pattern configured to draw in saliva passing through the first working electrode, the reference electrode, and the second working electrode.

19. The first working electrode is configured to detect sodium ions, The apparatus according to claim 18, wherein the second working electrode is configured to detect potassium ions.

20. The first working electrode includes a solid electrode, The apparatus according to claim 18, wherein the second working electrode includes a solid electrode.

21. The first working electrode comprises a wire coated with a composite coating and a sodium-selective film, The apparatus according to claim 18, wherein the second working electrode comprises a wire coated with a composite coating and a potassium-selective film.

22. The control circuit, From the sensor, data relating to the sodium ions based on the potential difference between the first working electrode and the reference electrode is obtained. From the sensor, data relating to the potassium ions based on the potential difference between the second working electrode and the reference electrode is obtained. The data relating to sodium ions and the data relating to potassium ions are transmitted to the end-user device. The apparatus according to claim 19, configured as described above.

23. A method for manufacturing the apparatus according to any one of claims 1 to 22, The process of forming the aforementioned flow channel, The steps include fixing the sensor, which is equipped with a first working electrode and a reference electrode, within the flow path, The steps include: coupling a control circuit to the aforementioned sensor in an operable manner; A step of fixing the flow path and the control circuit to the apparatus, A method that includes this.

24. The steps include fixing a second working electrode within the aforementioned flow path, A step of activating the control circuit to the second working electrode, The method according to claim 23, further comprising:

25. The process of forming the aforementioned flow channel is A step of aligning the inlet of the flow path with the opening of the device, The process involves forming a reservoir, a microfluidic channel leading from the inlet to the reservoir, and an outlet in a base layer of a hydrophilic material. A step of bonding the top layer to the base layer with medical-grade epoxy, Includes, The step of fixing the first working electrode includes the step of placing the first working electrode in the storage portion before bonding the top layer to the base layer, The method according to claim 24, wherein the step of fixing the second working electrode includes the step of placing the second working electrode in the reservoir before bonding the top layer to the base layer.

26. A method for determining the electrolyte levels of a patient, A step of detecting the level of electrolytes in saliva using the apparatus according to any one of claims 1 to 22, The process of transmitting the aforementioned level, A method that includes this.

27. ​​A step of detecting the level of the electrolyte using the apparatus according to any one of claims 1 to 22, The process involves continuously drawing saliva from the user's mouth into the reservoir of the channel, through the inlet of the channel equipped with a microfluidic channel. A step of acquiring a first signal from the first working electrode of the sensor, The first step is to compare the first signal with a reference signal from the reference electrode of the sensor, Includes, The method according to claim 26, wherein the first working electrode and the reference electrode are arranged within a capillary pattern contained inside the reservoir.

28. A step of acquiring a second signal from the second working electrode of the sensor, A step of comparing the second signal with the reference signal from the reference electrode, The method according to claim 27, further comprising:

29. A first potential difference is obtained by comparing the first signal with the reference signal. The process further includes a step of converting the first potential difference into the concentration of a first electrolyte based on a calibration coefficient, A second potential difference is obtained by comparing the second signal with the reference signal. The method according to claim 28, further comprising the step of converting the second potential difference into the concentration of the second electrolyte based on the calibration coefficient.

30. The first working electrode, the reference electrode, and the second working electrode each include a wire-type electrode. The reservoir comprises a plurality of rising members that form a capillary pattern configured to draw in saliva passing through the first working electrode, the reference electrode, and the second working electrode, The first electrolyte is sodium, and the second electrolyte is potassium. The first working electrode includes a solid electrode, The second working electrode includes a solid electrode, The first working electrode further comprises a wire coated with a composite coating and a sodium-selective film, The method according to claim 29, wherein the second working electrode further comprises a wire coated with a composite coating and a potassium-selective film.

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