Portable analysis device

Abstract

The present invention relates to a portable analysis device (1) comprising a handle (11), a measurement head (12) configured to be immersed in a urine sample, and further comprising: a. an electroanalysis cell comprising at least two electrodes including an immersion electrode; b. a light unit (14) configured to emit light into the urine sample; c. a multispectral optical sensor (13) configured to receive the light emitted by the light unit (14) through the urine sample.

Description

[0001] PORTABLE ANALYSIS DEVICE

[0002] FIELD OF INVENTION

[0003] The present invention relates to a portable device for analyzing biological fluids. In particular, the invention relates to a portable device for analyzing urine and methods for analyzing biological fluids such as urine.

[0004] STATE OF THE ART

[0005] Clinical tests performed on biological fluids, particularly urine or blood, are primarily conducted in medical laboratories using various machines that measure different parameters or concentrations of biomarkers. This method presents several drawbacks: logistical challenges, the need for highly qualified personnel, and expensive equipment. The main disadvantage of laboratory-based biological fluid analysis is the time required to obtain results. Samples must first be prepared and separated into multiple tubes for parallel testing on different machines measuring various parameters (optical or electrical), most often through chemical assays. The main drawback of chemical assays is sample deterioration. Subsequently, the results from each machine must be aggregated into a report and sent to the clinician.The results are generated a long time (4 to 48 hours) after the sample is taken, which delays diagnosis and generates unwanted and unnecessary stress for the patient.

[0006] Urine analysis is widely used for health monitoring and / or disease diagnosis, and is also performed using urine test strips, the results of which are read as color changes. This allows for a rapid test with a result generated in less than 10 minutes. However, this method requires a lot of disposable consumables and, more importantly, is inaccurate and can lead to false positives or false negatives. Even though urine strip tests can be considered a near-instant diagnostic test, these strips can lead to diagnostic errors, requiring further testing, unnecessary anxiety, and follow-up.

[0007] In this context, patent application EP 4016077 Al describes a portable urine analysis device comprising a handle and a measuring head configured to be immersed in a sample.

[0008] Therefore, there is a need for a biological fluid analysis device that allows for instant, comprehensive, and reliable diagnosis by simultaneously measuring multiple parameters in a sample. Combining several measurement techniques, such as optical and electrical measurements, using a single, reusable analysis device overcomes the aforementioned drawbacks.

[0009] SUMMARY

[0010] The invention relates to a portable analysis device comprising a handle, a measuring head configured to be immersed in a urine sample, the portable urine analysis device extending in an extension direction oriented from the handle towards the measuring head, the measuring head comprising an inner face and an outer face, the measuring head further comprising:

[0011] a. an electroanalytical cell comprising at least two electrodes, one of which is an immersion electrode;

[0012] b. a light unit configured to emit light into the urine sample;

[0013] c. a multispectral optical sensor configured to receive light emitted by the light unit through the urine sample;

[0014] wherein at least two electrodes of the electroanalytical cell are arranged on the external face of the measuring head; and the immersion electrode is closer to the handle than the light unit and the multispectral optical sensor in the direction of extension. In one embodiment, the electroanalytical cell comprises:

[0015] a measuring electrode;

[0016] a reference electrode; and

[0017] a counter electrode.

[0018] In one embodiment, the immersion electrode is the reference electrode. In another embodiment, the reference electrode is a platinum electrode. In one embodiment, the distance between the measuring electrode and the reference electrode is greater than the distance between the measuring electrode and the counter electrode; and the distance between the counter electrode and the reference electrode is greater than the distance between the counter electrode and the measuring electrode. In one embodiment, the electrodes of the electroanalytical cell have a contact surface area of ​​between 1 mm² 2 and 20 cm 2In one embodiment, the analysis device includes a rechargeable battery. In another embodiment, the analysis device further includes a wireless communication system capable of transferring data. In one embodiment, the light unit includes one or more light sources capable, as a whole, of emitting light with a wavelength between 340 nm and 2000 nm. In one embodiment, the analysis device further includes a temperature sensor. In one embodiment, the analysis device further includes a pH sensor.

[0019] The present invention also relates to a method for urine analysis comprising: a. collecting a urine sample in a container; b. immersing a portable analytical device according to the invention in said urine sample; c. measuring signals of the following physical properties of the sample: conductivity, voltammetry, amperometry, and / or potentiometry, and the NIR-visible spectrum, the IR spectrum, and / or the fluorescence spectrum; d. processing and analyzing the measured signals to determine the presence and / or concentration of a chemical species. In one embodiment, the method includes, before measuring the physical properties of the sample, calibrating the electroanalytical cell of the portable analytical device, the calibration comprising

[0020] i. the measurement of a test measure in the urine sample;

[0021] ii. the identification of a signal value associated with a predetermined chemical species present in urine;

[0022] iii. the calculation of a difference between the value of the test measurement signal and a predetermined value; and

[0023] iv. the calibration of the electroanalytical cell so as to correct the deviation.

[0024] According to one embodiment, the predetermined species is uric acid and the test measurement is a voltammetry measurement.

[0025] DEFINITIONS

[0026] In the present invention, the terms below are defined as follows:

[0027] "Autofluorescence spectrometry" is the measurement of the light emitted by a tissue or solution after excitation of that tissue or solution by light of a specific wavelength, particularly ultraviolet light.

[0028] "Electroanalytical methods," such as coulometry, potentiometry, amperometry, conductimetry, or voltammetry (or voltammetry), refer to electrochemical techniques used to characterize the reversibility of electron transfer and the impedance at the electrode-solution interface. For example, the term "conductimetry" can refer to the measurement of the electrolytic conductivity of a solution.

[0029] The term "IR" refers to the range of infrared wavelengths, from 780 nm to 10000 nm.

[0030] The term "NIR" refers to the range of wavelengths in the near-infrared, from 780 nm to 2500 nm, preferably from 780 nm to 1100 nm. The term "NIR-Vis" refers to the range of wavelengths in the near-infrared and visible, from 390 nm to 2500 nm, preferably from 390 nm to 1100 nm.

[0031] Near-infrared spectroscopy is a quantitative measurement of the absorbance of light in the near-infrared, that is, the ratio of light absorbed to light entering the near-infrared. This technique allows the detection of molecules that absorb low-energy radiation.

[0032] The term "UV" refers to ultraviolet light, from 190 nm to 400 nm, preferably from 270 nm to 400 nm.

[0033] Visible spectrometry refers to the characterization of a sample's light absorption in the visible spectrum. When extracting quantitative information, one typically measures the intensity of the light transmitted or reflected by the sample (I) and the intensity of a reference light (lo), which can represent:

[0034] the intensity of the light emitted by the source, the intensity of the light incident on the sample, or - the intensity of the light transmitted or reflected by a reference sample.

[0035] Calculations are thus performed and the ratio EIo (generally called transmittance) or the decimal logarithm of this ratio (generally called absorbance) are calculated.

[0036] DETAILED DESCRIPTION

[0037] The detailed description that follows will be better understood when read in conjunction with the drawings. For illustrative purposes, the device is shown in preferred embodiments. However, it should be understood that the present invention is not limited to the specific arrangements, structures, features, embodiments, and aspects illustrated. The drawings are not to scale and are not intended to limit the scope of the claims to the embodiments shown. Accordingly, it should be understood that when features mentioned in the appended claims are followed by reference numerals, these numerals are included solely to enhance the intelligibility of the claims and do not in any way limit their scope.

[0038] All examples and conditional language cited in this document are intended for educational purposes to assist the reader in understanding the principles of disclosure and the concepts brought by the inventor to the advancement of the art, and should be interpreted as not being limited to those specifically cited examples and conditions.

[0039] The present invention relates to a portable analysis device.

[0040] This analytical device comprises a handle, a measuring head configured to be immersed in a urine sample, the portable urine analysis device extending in a direction oriented from the handle towards the measuring head, the measuring head comprising an inner face and an outer face, the measuring head further comprising:

[0041] a. an electroanalytical cell comprising at least two electrodes, one of which is an immersion electrode;

[0042] b. a light unit configured to emit light into the urine sample;

[0043] c. a multispectral optical sensor configured to receive light emitted by the light unit through the urine sample;

[0044] in which at least two electrodes of the electroanalytical cell are arranged on the external face of the measuring head; and the immersion electrode is closer to the handle than the light unit and the multispectral optical sensor in the extension direction.

[0045] The analytical device enables non-invasive analysis of urine samples based on four technologies: visible spectrometry, near-infrared spectrometry (or infrared spectrometry), autofluorescence spectrometry, and conductimetry. It allows for a thorough physicochemical characterization of a urine sample.

[0046] The multispectral optical sensor is configured to receive light transmitted by the urine sample, such as visible and near-infrared light, allowing the analytical device to perform visible and / or near-infrared spectroscopy on the urine sample. With regard to visible spectroscopy, it is possible to detect biomarkers such as, for example, minerals (e.g., Na, K, Ca, Mg, Cl, P), creatinine, urea, urine osmolality, urine specific gravity, uric acid, urine pH, ammonium, citrate, oxalate, albumin, total protein, bilirubin, urobilinogen, red blood cells, white blood cells, ketone bodies, glucose, or the presence of bacteria or crystals.Near-infrared spectroscopy (NIRS) can detect biomarkers such as minerals (Na, K, Ca, Mg, Cl, P), creatinine, urea, urine osmolality, urine specific gravity, uric acid, urine pH, ammonium, citrate, oxalate, albumin, total protein, bilirubin, urobilinogen, red blood cells, white blood cells, ketone bodies, glucose, and the presence of bacteria or crystals. Urine osmolality and specific gravity are biomarkers of hydration, very useful for determining proper kidney function. Creatinine is also a biomarker that indicates proper kidney function.

[0047] The multispectral optical sensor is also configured to receive light emitted by the urine sample in order to anticipate urine autofluorescence, allowing the analytical device to perform autofluorescence spectrometry on the urine sample. Fluorescence spectrometry can detect biomarkers such as, for example, red blood cells, heavy metals, NADH (nicotinamide adenine dinucleotide hydrogen), NADPH (nicotinamide adenine dinucleotide phosphate), FAD (flavin adenine dinucleotide), elastin, collagen, tryptophan, porphyrins, riboflavin, or other endogenous fluorophores.

[0048] The optical sensor is also configured to receive light scattered within the urine sample, which is configured to detect light across a wide range of wavelengths. Preferably, the optical sensor comprises one or more light detectors.

[0049] Finally, the electroanalytical cell allows the analytical device to perform electrochemical measurements, such as conductivity, coulometry, potentiometry (such as chronopotentiometry), amperometry, or voltammetry (such as square wave voltammetry and cyclic voltammetry), on a biological sample. For example, the conductivity of urine results primarily from the mobility of the constituents (hydrated ions) present in the sample and thus provides a measure of the sample's ability to conduct an applied charge. Therefore, by measuring the conductivity of a biological sample, it is possible to determine the total concentration of ions in solution (e.g., Na₂). + K + , That 2+ , Mg 2+ , H + / CO 3' or Cl'). Other electroanalytical methods allow the analytical device to analyze uric acid, oxalate, citrate, nitrites, copper, pH, creatinine, bilirubin, albumin, amino acids such as tryptophan or tyrosine, BNP (brain natriuretic peptide), hormones such as beta-HCG, steroid hormones cortisol, anti-Müllerian hormone (AMH) or thyroid hormones, as well as markers of collagen degradation, in said sample.

[0050] The combination of biomarker detection by electroanalytical methods and optical spectrometry is particularly advantageous because it allows for a thorough yet rapid examination of the urine sample, simultaneously determining the presence / absence and / or concentration of several biomarkers in a single biological sample. It also provides better results—that is, greater accuracy and fewer false negatives—than processing optical and electroanalytical measurements separately. Furthermore, these measurements do not degrade the sample and can be repeated several times without impacting any subsequent assays. Finally, the simultaneous measurement of the sample temperature improves the accuracy of both optical and electroanalytical measurements.

[0051] For example, near-infrared spectroscopy and electroanalytical measurements are complementary for accurately determining the concentration of minerals (e.g., Na, K, Ca, Mg, Cl, P). Inorganic ions in aqueous solutions do not directly absorb near-infrared light but influence spectral patterns at specific wavelengths through interactions between the ions and water. Similarly, the saturation and crystallization of urine (e.g., the presence of calcium oxalate crystals) can be detected optically. Thus, the optical spectrum provides both qualitative and quantitative information. This initial estimation of the concentration of each mineral is complemented by an electroanalytical measurement, such as conductimetry, which reflects the total concentration of cations and anions in the solution, each ion having a specific molar conductivity.Furthermore, since ion mobility increases with temperature, simultaneous temperature measurement in addition to optical spectrum and electroanalytical measurement allows for an even more precise measurement of mineral concentration.

[0052] Furthermore, the visible, near-infrared, and infrared spectra contain specific wavelengths that are strongly associated with similar urinary biomarkers. Thus, combining this spectral information significantly improves the prediction of biomarker concentrations. For example, information about osmolality can be found below 700 nm, between 800 nm and 850 nm, around 1000 nm, around 1150 nm, and above 1200 nm, meaning that all ranges contain information, sometimes redundant and sometimes not, that can improve osmolality measurement. Finally, fluorescence spectroscopy is used to identify specific biomarkers in combination with visible spectra. For example, hematuria can cause a color change in urine from pale yellow to pink or red, detectable in the visible spectrum.

[0053] To perform biomarker detection, the analysis device is immersed in a urine sample so that the immersion electrode is submerged, activated to perform measurements, and then cleaned after use. Alternatively, a urine sample can be placed in a measuring cuvette within the measuring head, that is, between the two walls of the inner surface of the measuring head.

[0054] Advantageously, the immersion electrode is a marker located on the outer face of the measuring head, ensuring that the light unit and the optical sensor, both located on the inner face of the measuring head, are fully immersed in the sample to be analyzed. This allows for quick visual verification by the user, confirming the correct immersion of these components for optimal optical measurement.

[0055] The analysis device can also be used for the analysis of a biological sample other than urine such as, for example, blood, lymph, liquefied feces, adipose tissue, bone marrow, cerebrospinal fluid, sperm, umbilical cord blood, breast milk, tears or saliva.

[0056] The biological sample or urine can be provided by a human being or an animal, for example a bovine, a sheep, a pig, a horse or any other animal.

[0057] In one embodiment, the analysis device has a cylindrical shape. In a particular configuration of this embodiment, the device has the shape of a pen. This allows the device to be handheld, easy to use, and portable.

[0058] In one embodiment, the inner face of the measuring head comprises two walls, each housing the optical sensor and the light unit. The walls are opposite each other (i.e., facing each other) and extend in the direction of extension, so that the optical sensor and the light unit face each other. These two walls are separated by a gap, forming an optical path. This allows the urine to fill this gap between the walls, thus flooding the optical sensor and the light unit. The length of the optical path is particularly important because it determines the volume of sample that the light will pass through. A larger volume results in more information available for measurement. The optical path length can range from 1 mm to 30 mm, preferably from 5 mm to 20 mm.

[0059] In a particular configuration of this embodiment, one wall has a greater thickness than the other, in particular said thicker wall accommodates the light unit while the thinner wall accommodates the multi-spectral optical sensor.

[0060] In an alternative configuration of this embodiment, one wall has a greater thickness than the other, in particular said thicker wall accommodates the multispectral optical sensor while the thinner wall accommodates the light unit.

[0061] According to one embodiment, the electroanalytical cell is configured to use direct current.

[0062] In one embodiment, the electroanalytical cell is configured to measure conductivity, direct current, and / or alternating current (by conductimetry, voltammetry, potentiometry, coulometry, and / or amperometry) at one or more frequencies, said frequencies being in the range of 1 Hz to 1 MHz, preferably between 1 Hz and 200 kHz. In a preferred configuration of this embodiment, said frequencies are in the range of 10 Hz to 30 kHz. Higher frequencies would result in higher energy consumption and greater device complexity. Preferably, the electroanalytical cell is configured to measure the conductivity of a sample.

[0063] In one embodiment, the immersion electrode is closer to the handle than the other electrode of the electroanalytical cell. This embodiment advantageously ensures that, when the immersion electrode is level with or immersed in the sample, the other electrode of the electroanalytical cell is also immersed in the sample. This allows for faster and more accurate measurements.

[0064] According to one embodiment, the analysis device includes a proximal end, i.e. the end closest to the user, and the distance between this proximal end and the immersion electrode is between 5 cm and 30 cm, preferably between 15 cm and 20 cm.

[0065] According to one embodiment, the analysis device includes a distal end, i.e. the end furthest from the user and intended to be immersed in the sample, and the distance between this distal end and the immersion electrode is between 1 cm and 10 cm, preferably between 1 cm and 4 cm.

[0066] According to one embodiment, the distance between the immersion electrode and at least one other electrode of the electroanalytical cell is between 0.1 mm and 10 cm.

[0067] According to one embodiment, the ratio between the distance separating the immersion electrode from the proximal end of the device and the distance separating the other electrode of the electroanalytical cell from the proximal end of the device is between 0.1 and 10, preferably between 0.5 and 1.5.

[0068] According to one embodiment, the ratio between the distance separating the immersion electrode from the distal end of the device and the distance separating at least one other electrode of the electroanalytical cell from the distal end of the device is between 0.1 and 10, preferably between 0.5 and 3.

[0069] In one embodiment, the ratio between the distance from the immersion electrode to the proximal end of the device and the distance from the multispectral optical sensor to the proximal end of the device is between 0.2 and 5, preferably between 0.5 and 1.5. This embodiment advantageously ensures that, when the immersion electrode is level with or immersed in the sample, the light unit and / or the optical sensor are also fully immersed in the sample. This allows for faster and more accurate measurements.

[0070] In one embodiment, the ratio between the distance from the immersion electrode to the distal end of the device and the distance from the multispectral optical sensor to the distal end of the device is between 0.2 and 5, preferably between 0.5 and 1.5. This embodiment advantageously ensures that, when the immersion electrode is level with or immersed in the sample, the light unit and / or the optical sensor are also fully immersed in the sample. This allows for faster and more accurate measurements.

[0071] In one embodiment, the ratio between the distance from the immersion electrode to the proximal end of the device and the distance from the multispectral light unit to the proximal end of the device is between 0.2 and 5, preferably between 0.5 and 1.5. This embodiment advantageously ensures that, when the immersion electrode is level with or immersed in the sample, the light unit and / or the optical sensor are also fully immersed in the sample. This allows for faster and more accurate measurements.

[0072] In one embodiment, the ratio between the distance from the immersion electrode to the distal end of the device and the distance from the light unit to the distal end of the device is between 0.2 and 5, preferably between 0.5 and 1.5. This embodiment advantageously ensures that, when the immersion electrode is level with or immersed in the sample, the light unit and / or the optical sensor are also immersed in the sample. This allows for faster and more accurate measurements. In one embodiment, the electroanalytical cell comprises:

[0073] a measuring electrode;

[0074] a reference electrode; and

[0075] a counter electrode.

[0076] According to one embodiment, the immersion electrode corresponds to the reference electrode.

[0077] According to one embodiment, the reference electrode, the measuring electrode and / or the counter electrode is chosen from a platinum electrode, a steel electrode, a gold electrode, a gold alloy electrode, a graphite electrode, an Ag / AgCl electrode, a silver electrode, or an electrode comprising a boron-doped diamond (BDD) coating.

[0078] Preferably, the reference electrode is a platinum electrode

[0079] Preferably, the measuring electrode and / or the counter electrode is an electrode comprising a boron-doped diamond (BDD) coating

[0080] According to one embodiment, the distance between the measuring electrode and the reference electrode is greater than the distance between the measuring electrode and the counter electrode; and / or the distance between the counter electrode and the reference electrode is greater than the distance between the counter electrode and the measuring electrode.

[0081] According to one embodiment, the distance between the measuring electrode and the reference electrode is between 0.1 mm and 10 cm.

[0082] According to one embodiment, the distance between the measuring electrode and the counter electrode is between 0.1 mm and 10 cm.

[0083] According to one embodiment, the distance between the counter electrode and the reference electrode is between 0.1 mm and 10 cm. According to another embodiment, the electrodes of the electroanalytical cell have a contact surface area between 1 mm 2 and 20 cm 2 preferably between 5 mm 2 and 5 cm 2 , even more preferably between 5 mm 2 and 30 mm 2 .

[0084] In one embodiment, the external face of the measuring head includes a housing for each electrode of the electroanalytical cell, such that the electrodes are in contact with the sample. Preferably, these housings are holes and circular in shape. Advantageously, this allows the measuring surface of the electrodes to be in contact with the sample while integrating the electronics inside the measuring head.

[0085] In a preferred configuration, the electroanalytical cell is a conductivity probe. Specifically, this conductivity probe can be configured to measure the conductivity of direct current.

[0086] In an alternative configuration, the electroanalytical cell is a conductivity probe. Specifically, this conductivity probe can be configured to measure conductivity via electrochemical impedance spectroscopy.

[0087] According to one embodiment, the light unit comprises one or more light sources capable, as a whole, of emitting light with a wavelength between 340 nm and 2000 nm.

[0088] According to a specific configuration of this embodiment, the light unit comprises a NIR-Vis light source and emits light in a wavelength range between 390 nm and 1100 nm. The NIR-Vis light source can be an LED (light-emitting diode), a laser, a superluminescent LED (sLED), or an incandescent lamp.

[0089] According to a specific configuration of this embodiment, the light unit comprises a UV light source and emits UV light in a wavelength range between 190 nm and 400 nm, preferably between 270 nm and 400 nm, and preferably between 365 nm and 400 nm. The UV light source may be a UV LED (light-emitting diode), a laser, a superluminescent LED (sLED), or an incandescent lamp.

[0090] According to a specific configuration of this embodiment, the light unit includes an IR light source and emits IR light in a wavelength range between 800 nm and 2000 nm, preferably between 800 nm and 1350 nm.

[0091] According to one embodiment, the optical sensor is configured to collect light over a range of wavelengths from 400 nm to 2000 nm, preferably from 400 nm to 1100 nm.

[0092] According to one embodiment, the optical sensor is configured to collect light over a range of wavelengths between 800 nm and 2000 nm.

[0093] According to one embodiment, the optical sensor comprises at least one light detector, preferably two or more light detectors. In a specific configuration of this embodiment, the optical sensor comprises a first light detector collecting light over a wavelength range from 400 nm to 2500 nm, preferably from 400 nm to 1100 nm, i.e. a visible light collector, and a second light detector collecting light over a wavelength range from 800 nm to 10000 nm, preferably from 800 nm to 2600 nm, i.e. an infrared light collector.

[0094] According to one embodiment, the optical sensor is a miniaturized spectrometer or an interferometer.

[0095] In one embodiment, the analysis device further includes a temperature sensor. The temperature sensor measures the temperature of the urine sample, which is then converted into an electrical signal associated with that temperature. It also normalizes the optical and electrical signals.

[0096] In one embodiment, the analysis device further includes a pH sensor. The pH sensor measures the pH of the urine sample, which is then converted into an electrical signal associated with said pH. In a particular embodiment, the analysis device includes:

[0097] a. an electroanalytical cell comprising at least two electrodes, one of which is an immersion electrode;

[0098] b. a light unit configured to emit light into the urine sample;

[0099] c. a multispectral optical sensor configured to receive light emitted by the light unit through the urine sample;

[0100] d. a temperature sensor; and

[0101] e. a pH sensor;

[0102] in which at least two electrodes of the electroanalytical cell are arranged on the external face of the measuring head; and the immersion electrode is closer to the handle than the light unit and the multispectral optical sensor in the extension direction.

[0103] In one embodiment, the analysis device further comprises an ultrasonic sensor. This ultrasonic sensor provides information on the physical, mechanical, and chemical properties of the urine sample, such as density, the presence of cells, and / or crystals.

[0104] According to one embodiment, the analysis device further includes a sensor configured to perform Raman spectroscopy, electrochemical impedance spectroscopy or Fourier transform infrared (FTIR) spectroscopy measurement on the sample.

[0105] In one embodiment, the analysis device further includes a barcode reading system for identifying the sample container. In this embodiment, the sample container includes a barcode for identification purposes. Advantageously, this ensures identity verification so that results are attributed to the correct subject. Moreover, if numerous measurements are performed in parallel on separate samples, this automatic identification of each sample and the assignment of this identity to the results saves the user time, as they do not have to manually label each sample, and prevents human error in sample identification. In one embodiment, the analysis device includes optical filters. Advantageously, the optical filters allow:

[0106] the measurement of absorbance and / or fluorescence at specific wavelengths;

[0107] focusing light using optical lenses

[0108] the polarization of light to detect specific markers such as the presence of crystals.

[0109] In one embodiment, the analysis device is configured so that at least 10% of its length is immersed in a urine sample. In a particular configuration of this embodiment, the length of the analysis device configured to be immersed in the urine sample is between 10% and 50% of its total length.

[0110] According to one embodiment, the analysis device has a length between 5 cm and 30 cm, preferably between 10 cm and 25 cm, more preferably between 10 cm and 20 cm.

[0111] According to one embodiment, the analysis device has a width ranging from 1 cm to 10 cm, preferably from 1 cm to 5 cm, more preferably from 2 cm to 4 cm.

[0112] According to one embodiment, the measuring head has a length ranging from 0.5 cm to 10 cm, preferably from 0.5 cm to 5 cm, more preferably from 0.5 cm to 3 cm. Thus, the analysis device is configured to be immersed in a urine sample to a length ranging from 0.5 cm to 10 cm, preferably from 0.5 cm to 5 cm, more preferably from 0.5 cm to 3 cm.

[0113] According to one embodiment, the measuring head has a length between 3% and 80% of the length of the analysis device, preferably from 10% to 40% of the length of the analysis device, more preferably from 20% to 30% of the length of the analysis device.

[0114] According to one embodiment, the handle has a length ranging from 3 cm to 30 cm, preferably from 5 cm to 20 cm, more preferably from 10 cm to 15 cm. According to one embodiment, the handle has a length between 40% and 80% of the length of the analysis device, preferably from 50% to 70% of the length of the analysis device, more preferably from 55% to 65% of the length of the analysis device.

[0115] According to one embodiment, the analysis device further includes an activation button (also called the ON / OFF button) located at the end of the handle opposite the measuring head, also called the proximal end.

[0116] According to one embodiment, the analysis device includes a rechargeable battery.

[0117] In a specific configuration of this embodiment, the rechargeable battery is configured to operate for 24 hours without recharging. To conserve battery power, a sleep mode can be automatically activated when the device is not in use.

[0118] In another specific configuration of this embodiment, the rechargeable battery is configured to charge quickly, for example, the battery is fully charged after 1 hour.

[0119] In another specific configuration of this embodiment, the rechargeable battery has a size less than 2 cm x 6 cm.

[0120] According to one embodiment, the rechargeable battery is chosen from lithium-ion batteries, LiCF batteries xLi-FeS batteries, LiFePCU batteries, Li-SCh batteries, Li-b batteries, Li-Ag2CrÛ4, Li-Ag2V40n, Li-SVO, Li-CSVO, or lithium polymer batteries. Preferably, the rechargeable battery is a lithium-based battery.

[0121] In another embodiment, the analysis device further includes a non-rechargeable battery, for example an alkaline battery.

[0122] In another embodiment, the analysis device can be recharged by induction.

[0123] In one embodiment, the analysis device further comprises a wireless communication system capable of transferring data. In a specific configuration of this embodiment, the analysis device is configured to communicate wirelessly with a computing module such as, for example, a smartphone, tablet, or computer, via a wired or wireless connection (Bluetooth, Wi-Fi).

[0124] According to one embodiment, the analysis device is not disposable. The device is configured to be cleaned after use.

[0125] In one embodiment, the analytical device is made of or coated with a hydrophobic material. This embodiment is particularly advantageous because the analytical device does not require cleaning a solution between two samples.

[0126] According to one embodiment, the analysis device further includes a display module configured to display the data collected by the sensors / probes of the device and / or the results obtained after data processing.

[0127] According to one embodiment, the analysis device further includes a cap configured to cover the measuring head when the analysis device is not in use.

[0128] In one embodiment, the analysis device can be coupled to a cartridge configured to hold urine in a reservoir. The cartridge is configured to clip onto the measuring head of the analysis device so that the reservoir containing the urine is positioned between the walls of the inner face of the measuring head. In this embodiment, the electrodes of the electroanalytical cell are positioned on the inner face of the measuring head.

[0129] The present invention also relates to a method of urine analysis comprising: a. collecting a urine sample in a container; b. immersing an analytical device as described above in said urine sample; c. measuring signals of the following physical properties of the sample: - conductivity, voltammetry (such as, for example, square wave voltammetry and cyclic voltammetry), amperometry and / or potentiometry (such as, for example, chronopotentiometry), and - the NIR-visible spectrum, the IR spectrum and / or the fluorescence spectrum; d. processing and analyzing the measured signals to determine the presence and / or concentration of a chemical species.

[0130] The urine sample can be collected in any container.

[0131] The method described above can also be applied to a biological sample other than urine.

[0132] Before immersion, the analysis device can be switched on. In a specific configuration, said device also includes a first external LED, such as a blue LED, a green LED or a red LED, preferably a blue LED which indicates whether said device is switched on by emitting light.

[0133] Before immersion, the analysis device can also be connected to a computer module, such as a computer, smartphone or tablet, via a wireless connection.

[0134] The analytical device is then immersed in the sample so that the measuring head, including the electroanalytical cell, the optical sensor, and the measuring unit, are submerged. The user uses the immersion electrode, located on the external face of the measuring head so that it is visible and positioned higher than the optical sensor and the measuring unit relative to the distal end of the analytical device, to orient the device correctly. Therefore, if the immersion electrode is submerged, the optical sensor and the measuring unit will also be submerged.

[0135] To measure the physical properties of the urine sample, the immersed analysis device is activated by pressing the activation button. The device then performs optical and electroanalytical measurements.

[0136] In a specific configuration, the device also includes a second external LED, such as a blue LED, a green LED, or a red LED, preferably a green LED, which indicates whether the measurement was performed by emitting light and / or vibrating. The signals collected are then analyzed and processed to provide a readable representation to the user.

[0137] The method of the invention does not require the sample to be prepared, separated, or subjected to any treatment before inserting the sample container into the measuring base. Indeed, the analytical device can be immersed in the sample immediately after it is collected. However, the sample can be mixed with a reagent before immersing the analytical device. This reagent can be a fluorescent probe to detect the presence of molecules or cells of interest such as bacteria, leukocytes, glucose, sodium, calcium, chloride, hormones (beta-HCG, FMH, steroids), DNA, or RNA, or a signal amplifier such as gold nanoparticles to amplify the signal.

[0138] According to one embodiment, the method includes, before measuring the physical properties of the sample, calibrating the electroanalytical cell of the portable analytical device, the calibration comprising

[0139] i. the measurement of a test measure in the urine sample;

[0140] ii. the identification of a signal value associated with a predetermined chemical species present in urine or the use of the complete signal in another configuration;

[0141] iii. the calculation of a difference between the value of the test measurement signal and a predetermined value; and

[0142] iv. the calibration of the electroanalytical cell so as to correct the deviation.

[0143] According to one embodiment, the predetermined species is uric acid and the test measurement is a voltammetry measurement.

[0144] In a specific configuration, the predetermined species is uric acid detected around 500 mV and the test measurement is a cyclic voltammetry measurement.

[0145] In another specific configuration, the predetermined species is uric acid, detected around 500 mV, and the test measurement is a square wave voltammetry measurement. Uric acid detection utilizes a reduction peak (uric acid) around -1.2V–1.3V.

[0146] In another specific configuration, the predetermined species is uric acid, detected around 500 mV, and the test measurement is a square wave voltammetry measurement. Uric acid detection uses the entire spectrum versus a model of several specific species (gap analysis, 0V shift, etc.).

[0147] The method may further include a preliminary activation step which corresponds to cleaning the electrodes by passing a strong current between the reference and measuring electrode, controlled in voltage or current, for example, a + / - 2V (+ / -300mV) pulse, alternated 50 times at a frequency of 2.5Hz.

[0148] The present invention also relates to the use of the analysis device for the analysis of urine. This urine may be human or animal urine.

[0149] The present invention also relates to the use of the analysis device for the analysis of a biological sample such as, for example, blood, lymph, liquefied feces, adipose tissue, bone marrow, cerebrospinal fluid, sperm, umbilical cord blood, breast milk, tears or saliva.

[0150] All the above embodiments can be combined.

[0151] Although various embodiments have been described and illustrated, the detailed description should not be construed as being limited to the foregoing. Various modifications may be made to the embodiments by persons competent in the art without departing from the true spirit and scope of the disclosure, as defined by the claims. BRIEF DESCRIPTION OF FIGURES

[0152] Figure 1 A is a schematic side view of the analysis device 1 of the invention.

[0153] Figure IB is a schematic view of the analysis device 1 according to a first embodiment.

[0154] Figure 2 is a schematic view of the measuring head 12 of the analysis device 1 of the invention.

[0155] Figure 3A is a schematic side view of the analysis device 1 according to a second embodiment.

[0156] Figure 3B is a schematic side view of the analysis device 1 according to a third embodiment.

[0157] Figure 3C is another schematic side view of the analysis device 1 according to Figure 3A.

[0158] Figure 4 is a view of the analysis device 1 coupled to a cartridge 2.

[0159] Figure 5 is a view of cartridge 2.

[0160] Figure 6 is a view of cartridge 2.

[0161] ILLUSTRATIVE METHODS OF IMPLEMENTING THE INVENTION

[0162] As illustrated in Figures 1 AB, the analysis device 1 includes a handle 11 and a measuring head 12 configured to be immersed in a urine sample.

[0163] This measuring head 12 comprises an outer face 121 and an inner face 122. The measuring head 12 further comprises:

[0164] a. an electroanalytical cell comprising three electrodes (151, 152, 153) including an immersion electrode 151; b. a light unit 14 configured to emit light into the urine sample;

[0165] c. A multispectral optical sensor 13 configured to receive the light emitted by the light unit 14 through the urine sample. The electrodes of the electroanalytical cell (151, 152, 153) are arranged on the external face of the measuring head 12, and the immersion electrode 151 is closer to the handle 11 than the light unit 14 and the multispectral optical sensor 13 in the direction of extension.

[0166] Advantageously, when the measuring head is immersed in the sample, the immersion electrode 151, due to its superior position, will serve as a reference point to ensure that the other electrodes, the optical sensor and the light unit are properly immersed in the sample.

[0167] The analysis device 1 further includes an activation button 111 located at one end of the handle 11. Advantageously, the start of the measurement can be manually controlled by the user by pressing the activation button 111.

[0168] The inner face 122 comprises two parallel walls extending along the direction of the analytical device 1. These walls are separated by a gap, forming an optical path. This is particularly advantageous because it allows the urine to fill this gap between the walls, thus flooding the light unit 14 and the multispectral optical sensor 13. Furthermore, the length of the optical path created by the gap between the walls is crucial, as it determines the volume of the sample through which the light will pass. A larger volume provides more information for measurement.

[0169] This embodiment is particularly advantageous because the analysis device 1 allows for non-invasive examination of urine samples based on four technologies: visible spectrometry, near-infrared spectrometry, autofluorescence spectrometry, and conductimetry. It enables a thorough physicochemical characterization of a urine sample. In an embodiment illustrated in Figure 2, the electroanalytical cell of the analysis device 1 comprises:

[0170] an immersion electrode 151;

[0171] - a first electrode 152;

[0172] - a second electrode 153.

[0173] Preferably, the immersion electrode 151 is a reference electrode. The first electrode 152 and the second electrode 153 are chosen from a reference electrode and a counter electrode.

[0174] In an embodiment illustrated in figures 3A-C, the multispectral optical sensor 13 includes an infrared light detector 131 and a visible light detector 132.

[0175] According to Figure 3B, the analysis device 1 further includes a temperature sensor 16. The temperature sensor 16 measures the temperature of the urine sample, which is then converted into an electrical signal associated with that temperature. It also normalizes the optical and conductivity signals.

[0176] Advantageously, the simultaneous measurement of the temperature of the urine sample improves the accuracy of optical and conductimetric measurements.

[0177] In an embodiment illustrated in Figures 4-6, the analysis device 1 can be coupled to a cartridge 2. In this embodiment, two electrodes (not shown) of the electroanalytical cell are arranged on the outer face 121 of the measuring head, and three electrodes of the electroanalytical cell (151, 152, 153) are arranged on the inner face 122 of the measuring head 12. The urine is contained in a sealed cartridge 2 that can be slid between the two walls of the inner face 122 of the measuring head. The cartridge 2 comprises: an inlet port 22 configured for the passage of urine and connected to a reservoir 21 configured to hold urine; and two tabs 23 configured to communicate with the lateral faces of the measuring head 12, each tab comprising locking means 24 for locking the connection between the analysis device 1 and the cartridge 2.Cartridge 2 further includes at least two connectors 25 configured to make contact with the electrodes of the electroanalytical cell (151, 152, 153). Thus, cartridge 2 clips onto the measuring head 12 so that the reservoir of cartridge 21 is positioned between the two walls of the inner face 122 of the measuring head, and the connectors 25 of cartridge 2 are positioned opposite the electrodes of the electroanalytical cell (151, 152, 153). Optical and electroanalytical measurements can then be performed on the urine contained in cartridge 2, i.e., between the two walls of the inner face 122 of the measuring head.

[0178] EXAMPLES

[0179] The present invention will be better understood by reading the following examples which illustrate the invention in a non-limiting way.

[0180] Example 1:

[0181] Freshly collected urine samples were gathered in sterile 120 ml urine containers without additives or preservatives. To evaluate the analytical performance of the testing device, reference tests were performed by a central laboratory according to established methodologies.

[0182] The same samples were analyzed in parallel using the same analytical device to measure the optical spectrum (visible spectrometry, near-infrared spectrometry, autofluorescence spectrometry) and electroanalytical data. The numerical data were then processed by specific algorithms to determine concentration values ​​for each sample: on the one hand, concentration values ​​based on optical data, and on the other hand, concentration values ​​based on a combination of optical and electroanalytical data.

[0183] The concentrations determined by the reference equipment were then used as a control value and compared to the two concentration values ​​obtained by the analytical device: based on optical data and based on the combination of optical and electroanalytical data. Table 1 shows the correlations between the concentration of biomarkers with the reference devices and the results obtained by the analytical device with optical data, or with a combination of optical and electrical data.

[0184]

[0185] Table 1: Correlation between Gold Standard methodologies and the analytical device with or without electroanalytical data

[0186] We have observed that, compared to reference values, we obtain better accuracy in the predictions of our analysis device when the algorithms are used on a combination of optical and electroanalytical data rather than on optical data alone.

[0187] Example 2:

[0188] Freshly collected urine samples were gathered early in the morning. A selection was made from patients with urolithiasis to assess the presence of crystals in these urine samples. Each primary urine sample was collected in sterile 120 ml urine containers without additives or preservatives.

[0189] Urine samples are analyzed by the analysis device to characterize the physico-chemical profile obtained by optical analysis (visible spectrometry, near-infrared spectrometry, autofluorescence spectrometry) and electroanalysis (conductimetry) in order to determine the concentrations of the samples.

[0190] The urinary profiles measured using the analysis device are highly specific and vary from one individual to another. These variations depend on parameters such as individual health status and can be induced by pathologies such as urolithiasis, which leads to the formation of crystals in the urine.

[0191] During sample analysis, the data obtained by the instrument vary depending on the physicochemical parameters. For example, conductivity varies depending on the ionic concentration and the presence of crystals in the samples. In healthy individuals, conductivity ranges from 11.49 to 16.85 mS·cm⁻¹. 1 .

[0192] The conductivity value measured by the analysis device made it possible to identify samples at high risk of crystals (conductivity > 25 mS.cm'). 1 ) healthy samples and to adapt the algorithms predicting the concentration of biomarkers. The presence of crystals was confirmed by observing the urine samples with a contrast microscope equipped with a polarized light device.

[0193] DIGITAL REFERENCES

[0194] 1 - portable analysis device; 11 - handle; 111 - activation button; 12 - measuring head; 121 - external face; 122 - internal face; 13 - multispectral optical sensor; 131 - infrared light detector; 132 - visible light detector; 14 - light unit; 151 - immersion electrode; 152 - first electrode; 153 - second electrode; 16 - temperature sensor; 2 - cartridge; 21 - reservoir; 22 - inlet port; 23 - tab; 24 - locking means; 25 - connector

Claims

DEMANDS 1. Portable analysis device (1) comprising a handle (11), a measuring head (12) configured to be immersed in a urine sample, the portable urine analysis device (1) extending in an extension direction oriented from the handle (11) towards the measuring head (12), the measuring head (12) comprising an inner face and an outer face, the measuring head (12) further comprising: a. an electroanalytical cell comprising at least two electrodes, one of which is an immersion electrode; b. a light unit (14) configured to emit light into the urine sample; c. a multispectral optical sensor (13) configured to receive light emitted by the light unit (14) through the urine sample; wherein at least two electrodes of the electroanalytical cell are arranged on the external face of the measuring head (12); and the immersion electrode is closer to the handle (11) than the light unit (14) and the multispectral optical sensor (13) according to the extension direction.

2. Device according to claim 1, wherein the electroanalytical cell comprises: - a measuring electrode; - a reference electrode; and - a counter electrode.

3. Device according to claim 2, wherein the immersion electrode corresponds to the reference electrode.

4. Device according to any one of claims 2 or 3, wherein the reference electrode is a platinum electrode.

5. Device according to any one of claims 2 to 4 wherein: the distance between the measuring electrode and the reference electrode is greater than the distance between the measuring electrode and the counter electrode; and the distance between the counter electrode and the reference electrode is greater than the distance between the counter electrode and the measuring electrode.

6. A device according to any one of claims 1 to 5, wherein the electrodes of the electroanalytical cell have a contact surface area between 1 mm 2 and 20 cm 2 .

7. Device according to any one of claims 1 to 6 comprising a rechargeable battery.

8. Device according to any one of claims 1 to 7, further comprising a wireless communication system capable of transferring data.

9. Device according to any one of claims 1 to 8, wherein the light unit (14) comprises one or more light sources capable, as a whole, of emitting light whose wavelength is between 340 nm and 2000 nm.

10. Device according to any one of claims 1 to 9, further comprising a temperature sensor (16).

11. Device according to any one of claims 1 to 10, further comprising a pH sensor.

12. Method of urine analysis comprising: a. the collection of a urine sample in a container; b. immersion in said urine sample of a portable analysis device according to any one of claims 1 to 11; c. Measurement of signals with the following physical properties of the sample: ■ conductivity, voltammetry, amperometry and / or potentiometry, and ■ the NIR-visible spectrum, the IR spectrum and / or the fluorescence spectrum; d. The processing and analysis of the measured signals to determine the presence and / or concentration of a chemical species.

13. Method according to claim 12, comprising, prior to measuring the physical properties of the sample, the calibration of the electroanalytical cell of the portable analytical device, the calibration comprising i. the measurement of a test measure in the urine sample; ii. the identification of a signal value associated with a predetermined chemical species present in urine; iii. the calculation of a difference between the value of the test measurement signal and a predetermined value; and iv. the calibration of the electroanalytical cell so as to correct the deviation.

14. Method according to claim 13, wherein the predetermined species is uric acid and the test measurement is a voltammetry measurement.

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