Multi-sensor reusable salivary test device

Abstract

The invention relates to a reusable salivary test device (100) for measuring a plurality of different metabolic parameters of the human body, said device comprising at least one saliva collection carrier (10) and a plurality of sensors (20); each sensor (20) comprising at least one reference electrode (RE) and at least one working electrode (WE) in direct proximity to said reference electrode, each sensor being configured to measure a subset of parameters from among said parameters, and each sensor being separate from the other sensors (20).

Description

[0001] Reusable multi-sensor saliva testing device

[0002] technical field

[0003] The present invention relates to the field of devices for measuring and monitoring metabolic parameters of the human body, particularly by saliva testing, and more specifically concerns a reusable multi-sensor saliva testing device. The term "multi-sensor" refers to the presence of several independent sensors to measure different parameters (blood glucose, cholesterol, etc.).

[0004] The invention finds a direct, but not exclusive, application in the measurement and monitoring of the most frequent pathologies in humans such as diabetes, dyslipidemia, cardiovascular diseases and kidney diseases.

[0005] State of the art

[0006] Saliva testing devices have undergone significant evolution in recent decades, particularly in the area of ​​measuring human metabolic parameters. Historically, these devices were primarily designed for single-parameter testing, meaning they could only measure one parameter at a time. This limitation was largely due to the sensor technology available at the time and the constraints of miniaturization and component integration required for accurate measurements.

[0007] Among the existing solutions are saliva-based testing devices used to measure blood glucose. These devices typically use a single working electrode coupled to a reference electrode to detect glucose concentration in saliva. For example, the salivary glucose biosensor developed by Newcastle University in Australia uses electronic inks printed on a thin plastic film to measure glucose, thus eliminating the need for frequent blood tests. This device, while effective for diabetes management, is limited to measuring blood glucose levels only.

[0008] Similarly, saliva tests for cholesterol measurement use a similar approach, with specialized sensors to detect lipids in saliva. However, these devices suffer from the same limitations as those used for blood glucose: they are single-parameter and do not allow for a complete assessment of the patient's metabolic status. The development of multi-parameter devices has been hampered by several technical challenges. Integrating multiple sensors onto a single substrate, while ensuring separation and non-interference between them, has proven complex. For example, researchers at the University of Waterloo are working on nanomaterial-based sensors for salivary glucose detection. These sensors use materials such as copper oxide nanocubes to improve sensitivity and measurement accuracy.However, they still have to overcome challenges such as interference with other salivary compounds and the need for specific pH conditions for accurate results.

[0009] Multiparameter devices capable of measuring several parameters simultaneously are rare due to the technical complexity of integrating multiple sensors without mutual interference. For example, currently available saliva testing devices do not allow for a comprehensive and accurate assessment of metabolic parameters such as blood glucose, cholesterol, and other biomarkers of chronic diseases, which require regular monitoring with values ​​sufficient to assess disease progression and therapeutic effects. The challenge lies in calibrating and separating the sensors to avoid interference and ensure accurate and reliable measurements.

[0010] A notable example of this limitation is that even if a device were to include several electrodes intended to measure different parameters, such a device would lack precision due to interference between sensors and the difficulty of calibrating each sensor independently or due to the methodology used, often antibody-based, with a result in the form of a pink bar, which only gives an "all or nothing" result without precise values.

[0011] Moreover, as with the multi-drug saliva test marketed by MEDISUR (registered trademark), these existing devices are not reusable, requiring disposable components for each use, which increases costs and reduces convenience for users.

[0012] Despite significant advances in the development of saliva testing devices for specific parameters, existing solutions do not allow for the recurrent and simultaneous measurement of multiple metabolic parameters. This technological gap underscores the need to develop advanced devices capable of efficiently integrating multiple sensors, providing accurate and cost-effective readings, and offering a comprehensive assessment that includes projections and trends of the user's metabolic status for more effective diagnosis of chronic diseases and improved health management.

[0013] Summary of the invention

[0014] The present invention aims to overcome all or part of the drawbacks of the prior art described above by proposing

[0015] To this end, the present invention relates to a reusable saliva testing device for measuring several different metabolic parameters of the human body, said device comprising at least one saliva collection vector and a plurality of sensors. This device is remarkable in that each sensor: - comprises at least one working electrode in the direct vicinity of at least one reference electrode;

[0016] - is configured to measure a subset of parameters from among said parameters; and

[0017] - is separate from the other sensors.

[0018] The configuration with several separate sensors allows for precise and independent measurement of several metabolic parameters, avoiding interference between sensors.

[0019] According to one embodiment, the sensors are fixed on said device.

[0020] Fixed integration of sensors ensures structural robustness, durability and a reduction in the risk of malfunctions related to sensor movement or repositioning.

[0021] According to one aspect of the invention, all sensors are electrically connected to a central processing unit.

[0022] The central processing unit ensures centralized data management, facilitating the simultaneous processing of signals from multiple sensors for rapid diagnostics.

[0023] According to one aspect of the invention, each sensor incorporates at least one analyte, each analyte being associated with a parameter of the subset of parameters measured by said sensor.

[0024] The use of enzymes or mechanisms specific to each analyte ensures selectivity, allowing precise measurements for each targeted parameter.

[0025] According to a particular embodiment, each sensor incorporates two different analytes.

[0026] This configuration allows for multiple measurements on the same surface, optimizing sensor efficiency while reducing the device's footprint.

[0027] According to one embodiment, the sensors include analytes such as glucose, cholesterol, lactate, and urea.

[0028] These analytes cover a wide range of essential metabolic parameters, making the device versatile for various diagnostic applications, including diabetes, cardiovascular and renal diseases.

[0029] According to one embodiment, each sensor further comprises at least one counter electrode.

[0030] The counter electrode ensures electrochemical stability in the circuit, increasing the reliability and accuracy of measurements.

[0031] According to one embodiment, the sensors are of an electro-biochemical nature, producing an electrical signal, the device comprising a wireless communication module directly exploiting the electrical signal.

[0032] Wireless data transmission enables portable and connected use, facilitating real-time monitoring by external devices such as smartphones. In one embodiment, the device has a plurality of distinct faces, each face having at least one sensor.

[0033] The multi-sided layout maximizes the usable space of the device, allowing for a compact configuration and optimized access to the various sensors.

[0034] According to one embodiment, each sensor comprises a first working electrode and a second working electrode adjacent to each other, the first working electrode comprising the enzyme corresponding to the target analyte in saliva, and the second working electrode comprising no enzyme, said device being configured to subtract the signal from the second working electrode from the raw signal from the first working electrode in order to improve the quality of the measurement signal by reducing noise.

[0035] Subtracting the noisy signal significantly improves measurement quality, thereby increasing accuracy in environments with electrochemical interference.

[0036] The fundamental concepts of the invention having been set forth above in their most elementary form, other details and characteristics will become clearer upon reading the following description and in view of the attached drawings, giving by way of non-limiting example an embodiment of a multi-sensor saliva test device, in accordance with the principles of the invention.

[0037] Presentation of the drawings

[0038] The figures are provided for illustrative purposes only to aid understanding of the invention without limiting its scope. The various elements may be represented schematically and are not necessarily to scale. Throughout the figures, identical or equivalent elements are identified by the same numerical reference.

[0039] This is illustrated as follows:

[0040] [Fig. 1]: a schematic view of a multi-sensor saliva test device according to one embodiment of the invention;

[0041] [Fig. 2]: a block diagram of a sensor according to an embodiment of the invention;

[0042] [Fig. 3]: a simplified view of a set of sensors connected by a central unit according to an embodiment of the invention;

[0043] [Fig. 4]: a diagram of two sensors placed side by side sharing the same reference electrode;

[0044] [Fig. 5]: a diagram of four sensors placed side by side sharing the same reference electrode.

[0045] Detailed description of implementation methods

[0046] It should be noted that certain technical elements well known to those skilled in the art are reiterated here to avoid any insufficiency or ambiguity in the understanding of the present invention. The embodiment described below refers to a reusable, multi-sensor saliva testing device, primarily intended for the measurement and monitoring of certain common chronic pathologies. This non-limiting example is given for a better understanding of the invention and does not preclude the use of the device to measure other metabolic parameters of the human body.

[0047] Figure 1 represents a 100 multi-sensor saliva test device, simply modeled as a parallelepiped, comprising four sensors 20a to 20d, arranged on its four lateral faces.

[0048] Sensors 20a, 20b, 20c and 20d will be collectively designated by the reference 20.

[0049] Device 100 is configured to measure various metabolic parameters in the human body, simultaneously or one at a time, via saliva collected on at least one saliva collection vector not shown.

[0050] The saliva collection medium is, for example, an absorbent foam. Device 100 can be made from various medical-grade materials, such as biocompatible polymers, to ensure user safety and comfort. Furthermore, Device 100 is designed for reusability, with replaceable or cleanable sensors, to reduce costs and increase user convenience.

[0051] In particular, the 20 sensors are enzymatic sensors that are integrated into the device 100 and designed to retain their catalytic activity over a period of several weeks, up to 6 weeks, depending on storage and usage conditions.

[0052] Indeed, sustained use of the 20 sensors, for example every two minutes, allows them to be kept for one to two weeks, while moderate use, for example twice a day, allows their lifespan to be extended by several weeks.

[0053] This longevity is made possible by immobilizing the enzymes on stable and biocompatible supports, which limit their degradation and maintain their effectiveness through successive tests.

[0054] The reusability of the device means that the sensors can be used to perform multiple tests without requiring immediate replacement. The sensors are also designed for easy cleaning, thus extending their lifespan.

[0055] In case of wear or loss of efficiency, the sensors can be replaced, without having to replace the entire device.

[0056] Alternatives to the configuration shown in Figure 1 may include devices of various shapes, suited to different applications. For example, a portable, cylindrical device can be used for rapid testing in clinical or home settings. Similarly, a device consisting of groups of flexible strips would be more suitable for sports applications. Figure 2 shows a generic example of sensor 20 (corresponding to each of sensors 20a to 20d) used in device 100. This sensor is designed to measure a specific metabolic parameter from saliva and has an electronic architecture adapted for this purpose.

[0057] Each 20 sensor consists of a set of electronic components integrated on a card-shaped substrate.

[0058] According to the embodiment of Figure 2, each sensor 20 comprises two working electrodes WE1 and WE2, a reference electrode RE, and a counter electrode CE. These components are interconnected by conductive tracks.

[0059] The reference electrode RE is not mandatory on each sensor 20 of the device 100, so two or more sensors can share the same reference electrode as in the configurations of Figures 4 and 5.

[0060] Indeed, the only condition for operation is that at least one working electrode WE is placed in close proximity to a reference electrode RE.

[0061] In the illustrated example, the two working electrodes WE1 and WE2 are adjacent. These working electrodes enable the specific detection of analytes present in saliva. They are designed to interact electrochemically with the target analytes, generating an electrical signal proportional to the analyte concentration. They can also be used in other ways, for example, to improve the measurement accuracy of a single analyte, as will be described later.

[0062] The reference electrode RE is positioned immediately in close proximity to the working electrodes WE1 and WE2. It serves as a stable reference point for electrochemical measurements, ensuring a constant and reliable comparison of the potential variations generated by the working electrodes.

[0063] The CE counter electrode can complete the electrochemical circuit, providing the current flow necessary for the measurement reactions. The counter electrode thus maintains the electrical balance of the system, ensuring that the measurements remain accurate and reproducible.

[0064] Each sensor 20 is placed on a card which also has conductive tracks linking the different electrodes to the control and processing circuits located outside the illustrated area.

[0065] The architecture of the 20 sensors is optimized for large-scale manufacturing, using advanced electronic printing techniques to deposit conductive materials and electrodes onto the substrate. This manufacturing method enables the economical and reproducible production of sensors while maintaining high accuracy and sensitivity.

[0066] Figure 3 represents the sensors 20a to 20d placed on the same support and connected to a central processing unit 50. This common comb-shaped support is for example suitable for installation on a device 100 having several faces like that of Figure 1, each strip being able to be placed on one face of the device 100.

[0067] The common support also includes electrical tracks connected to the sensors 20. Thus, the sensors 20 remain spatially separated and their arrangement can be carried out in different forms.

[0068] The physical separation of sensors 20 also includes the situation in which two or more sensors are joined together while keeping their essential components separate, as in Figures 4 and 5.

[0069] The conductive tracks ensure the transmission of electrical signals generated by electrochemical reactions to the processing circuits, where they are analyzed to determine the concentrations of analytes and therefore also allow this information to be transmitted by radio to an external terminal such as a smartphone.

[0070] As an example, sensor 20a, located on the front face of the cube, could be configured to measure glucose concentration in saliva. This sensor uses at least one working electrode (WE) and one reference electrode (RE), positioned in close proximity to each other, to accurately detect glucose levels. Saliva, containing trace amounts of glucose, comes into contact with the electrodes, thus enabling a measurable electrochemical reaction.

[0071] The 20a sensor, configured to measure glucose concentration in saliva, is designed so that saliva is directed to the electrodes via a sampling vector, such as an absorbent foam. This foam captures the user's saliva upon contact with the mouth. Once the saliva is absorbed by the foam, it is compressed to deliver the saliva to the working (WE) and reference (RE) electrodes, which are located in close proximity to each other, or even to the CE electrode.

[0072] The foam plays a crucial role by filtering bubbles, distributing saliva throughout the foam, and maintaining constant contact between the saliva and the electrodes, thus ensuring that the necessary amount of liquid for the electrochemical reaction is present. This reaction occurs when the enzyme reacts with glucose in the saliva. The resulting electrochemical signal is proportional to the glucose concentration and is considered "measurable" because it can be analyzed by the device's electronic circuits to provide an accurate reading.

[0073] Sensor 20b, located on the right side of the cube, could be used to measure cholesterol levels. Using specific electrodes, this sensor can interact with lipid compounds present in saliva, providing data on the user's lipid profile. This measurement can be used, for example, to assess the risk of cardiovascular disease.

[0074] The 20c sensor, located on the back of the cube, could be designed to measure electrolytes, such as sodium, potassium, or calcium. The levels of these electrolytes are essential for monitoring kidney function and the body's electrolyte balance. The sensor uses a combination of electrodes to detect changes in electrolytes in saliva.

[0075] The 20d sensor, positioned on the left side of the cube, could be configured to detect inflammatory markers. These markers, such as C-reactive protein (CRP), can indicate inflammatory or infectious conditions in the body.

[0076] According to one embodiment, the sensors 20 are of an electrobiochemical nature, producing an electrical signal, this signal is directly used by a wireless communication module for data transmission.

[0077] These electro-biochemical sensors are designed to detect various analytes present in saliva, such as glucose, cholesterol, or other metabolic biomarkers. The electrodes of the sensors are arranged on a substrate that also includes conductive tracks.

[0078] When a saliva sample comes into contact with the electrodes, an electrochemical reaction is triggered. This reaction generates an electrical signal proportional to the concentration of the target analyte. The conductive tracks integrated into the substrate then ensure the collection and transmission of this electrical signal. They connect the electrodes to the processing circuits integrated into the device.

[0079] The electrical signal thus generated is processed by an electronic module that analyzes the data to determine the specific concentrations of the analytes. This processing may include amplification, filtering, and conversion of the signal into a usable digital format. Once the data is processed, it is ready for transmission.

[0080] To this end, the 100 device is equipped with a wireless communication module, for example using Bluetooth Low Energy (BLE) technology, which allows information to be transmitted directly to an external device such as a smartphone, tablet, or computer. This communication module is designed to directly utilize the electrical signal produced by electrochemical reactions, without requiring complex conversion or additional interfaces. Wireless data transmission offers increased flexibility and convenience for the user, enabling real-time monitoring of metabolic parameters via a mobile application or dedicated software.

[0081] According to one embodiment, each sensor 20 comprises a first working electrode WE1 and a second working electrode WE2 positioned side by side. The first working electrode WE1 is functionalized with an enzyme specific to the target analyte, for example, a glucose oxidase enzyme if the analyte is glucose. This enzyme catalyzes an electrochemical reaction when it comes into contact with the analyte present in saliva, thus producing an electrical signal proportional to the concentration of that analyte.

[0082] The second working electrode, WE2, contains no enzymes. It is configured to be exposed to the same environmental conditions as the first electrode, but without directly interacting with the analyte. Consequently, any signal generated by WE2 is primarily due to background noise or nonspecific interference present in the salivary medium.

[0083] Device 100 is configured to subtract the WE2 signal from the raw signal generated by WE1. By performing this subtraction, the device effectively eliminates background noise, retaining only the signal specific to the analyte of interest.

[0084] Furthermore, this noise subtraction using the two working electrodes can be applied in a single-sensor saliva test device allowing the measurement of a single parameter of the human body.

[0085] According to another embodiment, the device 100 can be configured to operate with different electrode architectures, depending on the currents measured, the analytes targeted and the measurement medium (e.g. saliva, interstitial fluids, sweat, etc.). Two main configurations can be envisaged.

[0086] In a first configuration, the sensor 20 uses a two-electrode architecture, where the counter electrode CE also fulfills the role of the reference electrode RE. This simplification reduces the complexity of the device, while remaining suitable for the need.

[0087] In a second configuration, a three-electrode architecture is adopted, with a counter electrode CE separate from the reference electrode RE, in addition to the working electrode WE.

Claims

DEMANDS 1. Reusable saliva test device (100) for measuring several different metabolic parameters of the human body, said device comprising at least one saliva collection vector (10) and a plurality of sensors (20), and characterized in that each sensor (20) - includes at least one working electrode (WE) in the direct vicinity of at least one reference electrode (RE); - is configured to measure a subset of parameters from among said parameters; - is separated from the other sensors (20); and - can be used to perform multiple tests without requiring replacement.

2. Device according to claim 1, wherein the sensors (20) are fixed on said device.

3. Device according to claim 1 or 2, wherein all the sensors (20) are electrically connected to a processing unit (50).

4. Device according to any one of the preceding claims, wherein each sensor (20) incorporates at least one analyte, each analyte being associated with a parameter of the subset of parameters measured by said sensor.

5. Device according to any one of the preceding claims, wherein each sensor (20) incorporates two different analytes.

6. Device according to any one of the preceding claims, wherein the sensors (20) comprise analytes including glucose, cholesterol, lactate, and urea.

7. Device according to any one of the preceding claims, wherein each sensor (20) further comprises at least one counter electrode (CE).

8. Device according to any one of the preceding claims, wherein the sensors (20) are of an electro-biochemical nature, producing an electrical signal, said device comprising a wireless communication module directly exploiting the electrical signal.

9. Device according to any one of the preceding claims, having a plurality of distinct faces and comprising on each of said faces at least one sensor (20).

10. A device according to any one of the preceding claims, wherein each sensor (20) comprises a first working electrode (WE1) and a second working electrode (WE2) adjacent to each other, the first working electrode (WE1) comprising the enzyme corresponding to the target analyte in saliva, and the second working electrode (WE2) not comprising any enzyme, said device being configured to subtract the signal from the second working electrode (WE2) from the raw signal from the first working electrode (WE1) in order to improve the quality of the measurement signal by reducing noise.

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