Microfluidic electrochemical device for measuring volumetric flow rates

Abstract

The present invention is directed to microfluidic channels 11a, 11b, and 11c, and a distance L between electrodes in the direction of fluid flow in the microfluidic channels. a ,L b ,L c The present invention relates to a microfluidic electrochemical device including an electrochemical cell 14a, 14b, 14c having a pair of first working electrodes WE1, WE2 spaced apart by a distance θ, a counter electrode CE, and a reference electrode REF. The microfluidic electrochemical device includes an electrochemical amperometric measurement system 15 that biases the pair of working electrodes, each of which generates an amperometric signal due to an oxidation or reduction reaction of the electroactive fluid or a chemical species corresponding to a redox couple for the fluid. The microfluidic electrochemical device determines the volumetric flow rate of the fluid within the microfluidic channel based, among other things, on the distance between the electrodes and the time delay between the amperometric signals generated by the pair of working electrodes.

Description

[Technical Field]

[0001] The present invention relates to the field of microfluidic electrochemical devices and methods for measuring the volumetric flow rate of an electroactive fluid or a fluid containing one or more electroactive species within a microfluidic channel. More generally, the present invention relates to an apparatus for determining quantitative sweat parameters in a human or animal subject. [Background technology]

[0002] Sweat is secreted by sweat glands in the skin, excreted through skin pores, and evaporated through the epidermis. Sweating plays an important role in a subject's biology, as it allows the body to regulate temperature. Excessive sweating can cause a subject to become dehydrated, impairing physical performance and potentially having detrimental effects on health. Excessive fluid intake can also cause hyponatremia, fatigue, confusion, coma, and even death in a subject.

[0003] Various devices are known in the prior art for measuring minute flow rates in situ, including, inter alia, thermal flow sensors and Coriolis effect microflowmeters. In practice, these devices are expensive, suffer from unresolved reliability issues, and are generally built into bulky units. More specifically, microfluidic devices have been developed to measure minute flow rates of sweat excreted from a human or animal subject and circulating within a microfluidic channel. Measuring sweat microflow allows for the proper assessment of a subject's quantitative sweating parameters, which can be used, for example, to monitor a subject's hydration level to prevent fluid imbalance in the body, particularly in athletes and the elderly, and to diagnose hypohidrosis, a sweating disorder characterized by insufficient sweat production, which can be caused by medical conditions that can impair sweat gland function (e.g., diabetes, alcoholism, Parkinson's disease, Ross syndrome, Sjogren's syndrome, small cell lung cancer, etc.), dermatological causes (e.g., burns, inflammation, infections, skin diseases), pharmaceutical causes (e.g., anticholinergic drug treatment), and genetic causes (e.g., hypohidrotic ectodermal dysplasia).

[0004] Known microfluidic devices offer the advantage of easily collecting sweat with very high temporal resolution without evaporation within the microfluidic channels. Colorimetric methods are generally preferred because the associated devices are easy to fabricate. However, most of the drawbacks of colorimetric methods are related to the irreversible nature of the method. Once a microfluidic channel is filled with sweat, the device is permanently altered by the dye and cannot be reused. This situation is also true for detection techniques based on electrically transduced signals such as resistance, conductance, capacitance, or impedance. To estimate the sweat microflow rate, it is necessary to monitor the channel filling rate using multiple electrodes arranged along the microfluidic channel. Once filled, a microfluidic channel cannot be reused.

[0005] In French patent application FR 3 103 901, hydrogen peroxide H2O2, nitric oxide NO or nitrite ions NO2 are specifically contained in sweat streams. - A method for measuring sweat flow rate is described that is based on the delay between time variations of the amperometric signal, which itself is indicative of the concentration of Summary of the Invention

[0006] One idea behind the present invention is to provide a microfluidic electrochemical device for measuring the volumetric flow rate of a fluid in a microfluidic channel without the need to determine the concentration of electroactive species contained in the fluid stream.

[0007] Another idea behind the present invention is to provide a flexible device that adheres to the skin to determine quantitative sweat parameters of a subject based on continuous in situ measurement of the volumetric flow rate of sweat through a microfluidic channel.

[0008] An object of the present invention is to provide such an apparatus which offers the additional advantages of space saving, simple design and low cost.

[0009] In one embodiment, the present invention provides a microfluidic electrochemical device for measuring flow rate and / or volumetric flow rate of a fluid comprising a solvent, comprising: - at least one microfluidic channel configured to direct said fluid in a flow direction; - at least one electrochemical cell disposed in the at least one microfluidic flow channel, the electrochemical cell comprising a first working electrode, at least one second, at least one counter electrode, and at least one reference electrode, wherein the at least one second working electrode is spaced apart from the first working electrode in the flow direction by an inter-electrode distance; an electrochemical amperometric measurement system biasing the first working electrode at a first electrode potential and biasing the second working electrode at the second electrode potential, such that the first working electrode and the second working electrode each generate an amperometric signal through an oxidation or reduction reaction of the solvent or of at least one chemical species that forms a redox pair with the solvent; It is equipped with The electrochemical amperometry measurement system is configured to determine a flow velocity and / or a volumetric flow rate of the fluid in the microfluidic channel based on the electrode distance and a time delay between a variation in the amperometry signal caused by the first working electrode and a variation in the amperometry signal caused by the second working electrode.

[0010] Such microfluidic electrochemical devices can be incorporated into numerous microsystems for in situ measurement of volumetric flow rate and / or flow velocity of fluids in microfluidic channels, such as lab-on-a-chip microfluidic platforms or μTAS systems (micro-Total Analysis Systems).

[0011] Microfluidic electrochemical devices are easy to fabricate and industrialize because they have no moving parts and no assumptions need to be made about the hydrodynamic conditions of fluid flow within the microfluidic channels. Measurement of flow rate and / or volumetric flow rate has no bearing on measurements of the concentration of chemical species produced or contained in the fluid, but only on the response time between fluctuations in the amperometric signal of a pair of working electrodes.

[0012] In some embodiments, the microfluidic electrochemical device described above may include one or more of the following features:

[0013] In one embodiment, the solvent is water HO (l) is.

[0014] Water acts as the reducing species in the O2 / H2O redox couple, and H3O + It can act as an oxidizing species in the / H2 redox couple.

[0015] In one embodiment, the fluid is sweat from a human or animal subject.

[0016] In one embodiment, the first electrode potential is water HO (l) is oxidized to dioxygen O 2(aq) The second electrode potential can reduce the dioxygen O2 dissolved in the produced water H2O to water H2O.

[0017] Water HO at the first working electrode (l) and the reduction of dioxygen O2(aq) at the second working electrode by selecting appropriate potentials applied to the first and second working electrodes, the amplitude of the amperometric signal detected at each working electrode can be controlled to maintain a sufficient signal-to-noise ratio to facilitate detection of fluctuations in the amperometric signal without having to measure the amplitude of the amperometric signal detected at said working electrodes.

[0018] In one embodiment, the first electrode potential is water HO (l) is reduced to dihydrogen H 2(aq) The second electrode potential can be (l) is reduced to dihydrogen H 2(aq) It can be made into.

[0019] In one embodiment, the first electrode potential is water HO (l) Dioxygen dissolved in 2(aq) is reduced to water H2O (l) The second electrode potential can be (l) Dioxygen dissolved in 2(aq) is reduced to water H2O (l) It can be made into.

[0020] In one embodiment, the electrochemical amperometric measurement system comprises: - in a first step, biasing the first working electrode at a first electrode potential and biasing the second working electrode at the second electrode potential; In a second step, the first working electrode is disconnected or the first electrode potential is set to a potential close to or equal to the zero current equilibrium potential.

[0021] In one embodiment, the microfluidic electrochemical device further comprises an insulating support, wherein the at least one microfluidic channel is formed in the insulating support, and the first and second working electrodes are formed by metal deposits of platinum or platinum black on the insulating support.

[0022] In one embodiment, the counter electrode is positioned downstream from the working electrode in the flow direction, and the reference electrode is positioned upstream from the working electrode in the flow direction.

[0023] In this way, to maintain the stability of the reference electrode potential over time, the reference electrode is positioned upstream of the pair of working electrodes and the counter electrode is positioned downstream of the pair of working electrodes, thereby ensuring that chemical species generated on the surface of the reference electrode do not inhibit either the working or reference electrodes.

[0024] Advantageously, the surface area of the counter electrode is two to three times the surface area of the other electrode.

[0025] In some embodiments, the microfluidic electrochemical device can include one or more microfluidic flow channels. Where applicable, an electrochemical cell can be disposed within one or each microfluidic flow channel, or within some or all of the microfluidic flow channels. The electrochemical cells disposed within different flow channels can be different or identical. Each redox reaction realized in the electrochemical cells disposed within different flow channels can be different or identical.

[0026] In one embodiment, the microfluidic electrochemical device further comprises a first microfluidic flow path and a second microfluidic flow path, wherein the first electrochemical cell is disposed in the first microfluidic flow path and the second electrochemical cell is disposed in the second microfluidic flow path, and the inter-electrode distance of the first electrochemical cell is different from the inter-electrode distance of the second electrochemical cell.

[0027] In one embodiment, the at least one electrochemical cell includes two second working electrodes, each separated from the first working electrode by a first inter-electrode distance and a second inter-electrode distance different from the first inter-electrode distance.

[0028] Preferably, the inter-electrode distance separating the pair of working electrodes is small enough to cause negligible changes in the subject's physiological response over the duration of the time delay between fluctuations in the amperometric signal of the working electrodes, and is sufficient to allow for uncoordinated operation patterns of the working electrodes in at least one of the microfluidic channels.

[0029] In fact, the coupled or uncoupled movement pattern of the working electrodes depends on the average flow velocity of the fluid in the microfluidic channel and the inter-electrode distance. When the flow velocity is high and the inter-electrode distance is too small, the flow of the fluid reacted at the first working electrode remains inhomogeneous even after reaching the second working electrode. This coupled pattern limits the time resolution of the amperometric signal, thereby reducing the accuracy of sweat volumetric flow measurement.

[0030] In one embodiment, the electrochemical amperometry measurement system is configured to determine the volumetric flow rate as a function of a cross-sectional area of the microfluidic channel in the flow direction.

[0031] In this way, by setting the electrode distance differently depending on the electrochemical cell in question, volumetric flow rates can be measured over a range of values that covers all possible physiological flow rates.

[0032] In one embodiment, the present invention provides a device for placement on an investigation zone of the epidermis of a human or animal subject for measuring quantitative sweat parameters of the subject, the device comprising: a structure forming a microfluidic electrochemical device, the structure comprising an inlet defining the investigation zone and enabling at least one microfluidic flow channel of the microfluidic electrochemical device connected to the inlet via perspiration from the epidermis; an electronic processing unit configured to determine quantitative sweat parameters of said human or animal subject based on the sweat volumetric flow measurements made by said microfluidic electrochemical device.

[0033] The quantitative sweat parameter may be a sweat rate determined based on the total volume of sweat secreted by the subject over a specified time range relative to the surface area of the investigation zone.

[0034] In one embodiment, the quantitative sweat parameter of said human or animal subject is sweat rate.

[0035] "Epidermis" means the surface layer of the skin of humans and animals.

[0036] In some embodiments, the above device may include one or more of the following features:

[0037] In one embodiment, the structure is a multi-layer structure having a bottom layer and at least one layer stacked on the bottom layer, the microfluidic electrochemical device extending parallel to the bottom layer, and the bottom layer having the inlet.

[0038] In one embodiment, the multilayer structure further comprises an upper layer and at least one intermediate layer disposed between the lower layer and the upper layer, and the microfluidic electrochemical device is formed within the thickness of the at least one intermediate layer.

[0039] The layers may be attached to one another using any suitable technique, such as adhesives, soldering, mechanical clamps, or the like.

[0040] Such a configuration makes the device easier to manufacture and assemble, and therefore easier to industrialize.

[0041] This configuration allows the device to conform to the curvature that may occur when applied to the epidermis. Furthermore, the one or more intermediate layers can provide a thickness that compensates for the thickness of the electrodes of the microfluidic electrochemical device, thereby ensuring that the device is waterproof.

[0042] In one embodiment, the top layer has an outlet extending therethrough, and the at least one microfluidic channel is connected to the outlet.

[0043] In one embodiment, the first working electrode, the at least one second working electrode, the at least one counter electrode, and the at least one reference electrode are disposed on an inner surface of the upper layer to block the at least one microfluidic channel from above, and / or are disposed on an upper surface of the lower layer to block the at least one microfluidic channel from below.

[0044] This configuration allows for reliable electrode placement and, when forming microfluidic electrochemical devices in the intermediate layers, facilitates the fabrication of multilayer structures with these electrodes, since the electrodes can be fabricated on planar layers.

[0045] In one embodiment, the apparatus further comprises a wired or wireless communication device for transmitting one or more measurement signals generated by the microfluidic electrochemical device.

[0046] In one embodiment, the device further comprises a gyroscope module and / or at least one accelerometer for detecting an activity state of the human or animal subject.

[0047] In one embodiment, the device further comprises a temperature sensor for measuring the temperature of the epidermis of the human or animal subject.

[0048] In one embodiment, the device comprises a geolocation module.

[0049] With this configuration, the device is configured to perform measurements periodically, for example at a configurable frequency or at a frequency that depends on the activity state detected by the device, to facilitate analysis of the correlation between the subject's activity state and the subject's quantitative sweat parameters measured by the device.

[0050] Measurement of sweat volume flow rate and / or quantitative sweat parameters can be used in a variety of applications, such as for monitoring a subject's hydration level to diagnose exercise-induced body fluid imbalance, particularly in athletes, or in the elderly, in hot climates, or hypohidrosis regardless of cause.

[0051] Other applications are possible in various technical or environmental fields, wherever measurement of flow rate is required in devices or processes using electroactive fluids or processes involving one or more electroactive species.

[0052] The present invention can be better understood, and other objects, details, features and advantages of the present invention can be more clearly seen, by reading the following several specific embodiments of the present invention in their entirety with reference to the accompanying drawings, which are given by way of non-limiting example only. [Brief explanation of the drawings]

[0053] [Figure 1] 1 is a schematic rear view of a subject on which an apparatus according to an embodiment is placed. [Figure 2] FIG. 1 is a perspective view of a portion of a multi-layer structure of an embodiment of the device. [Figure 3] FIG. 3 is a cross-sectional view taken along line III-III in FIG. 2. [Figure 4] FIG. 1 is an exploded view of a multi-layer structure of one embodiment. [Figure 5] 1 is a schematic partial functional diagram of a multilayer structure forming an electrochemical device in a device. [Figure 6]FIG. 1 is a schematic partial functional diagram of a microfluidic electrochemical device that can be used in the apparatus. [Figure 7] 1 is a schematic top view of an electrochemical cell of a first embodiment. FIG. [Figure 8] FIG. 8 is a schematic diagram similar to FIG. 7 of a second embodiment. [Figure 9] 1 is a schematic functional cross-sectional view along a microfluidic channel of an electrochemical cell of a first embodiment. FIG. [Figure 10] 8 is a set of chronoamperograms illustrating a method that can be performed in accordance with the first embodiment, in conjunction with the microfluidic electrochemical device of FIG. 7. [Figure 11] FIG. 10 is a schematic functional diagram similar to FIG. 9, of a second embodiment. [Figure 12] 11 is a set of chronoamperograms similar to FIG. 10 for the second embodiment. [Figure 13] FIG. 12 is a schematic functional diagram similar to FIGS. 9 and 11 of a third embodiment. [Figure 14] 13 is a pair of chronoamperograms similar to those of FIGS. 10 and 12 for the third embodiment. [Figure 15] FIG. 2 is a schematic functional diagram of an electronic control unit that can be implemented in conjunction with the device; DETAILED DESCRIPTION OF THE INVENTION

[0054] The embodiments described below relate to an apparatus for determining quantitative sweat parameters of a subject by continuously measuring the volumetric flow rate of sweat in a microfluidic channel using a microfluidic electrochemical device. More generally, such microfluidic electrochemical devices can be incorporated into a number of microsystems for in situ measurement of the average flow rate of an electroactive fluid in a microfluidic channel. Such microsystems can be, for example, lab-on-a-chip microfluidic platforms or μTAS (micro-total analysis systems) systems.

[0055] 1, a device 1 for determining quantitative sweat parameters is placed on the skin 2 of a human subject, for example on the subject's back. In a variant not shown, the device 1 can be placed on the skin of an animal subject.

[0056] 2, the device 1 takes the form of a space-saving multi-layer structure made of waterproof material, such as a polymer material, comprising a lower layer 3 made of a flexible, biocompatible material and an insulating support 4 superimposed on the lower layer 3, the material of which is preferably a self-adhesive material, such as polyethylene terephthalate (PET), that can be placed directly on the skin 2 of the subject.

[0057] A microfluidic channel 11 is formed by hollowing out the thickness of the insulating support part 4. A sampling cup 5 is formed in the lower layer 3 at a position aligned with the circular opening 6.

[0058] Referring to FIG. 3 , the bottom layer 3 is adhered to the skin 2 by an adhesive layer 7. A circular opening 6 is provided in the central portion of the bottom layer 3 and the central portion of the adhesive layer 7, and defines an investigation zone 8 on the subject's skin 2. The circular opening 6 may have any other shape, such as an oval, triangle, rectangle, square, or polygon. The circular opening 6 forms an inlet 6 for guiding a sweat flow 9, particularly for transporting sweat to a microfluidic channel 11. The sweat flow 9 flows from the subject's skin 2 through the circular opening 6 and into the microfluidic channel 11.

[0059] A hydrophilic collecting element (not shown), such as a fibrous material such as cotton or nonwoven fabric, can be placed within the circular opening 6 and within the sampling cup 5. This collecting element transports the sweat produced in the investigation zone 8 to the microfluidic electrochemical device 100.

[0060] Referring to Figure 4, in the first embodiment, the multilayer structure of the device 1 has a lower layer 3 having an inlet 6 for sweat passage, an upper layer 10 having an outlet 22, and an intermediate layer 4 arranged between the lower layer 3 and the upper layer 10, and the microfluidic electrochemical device 100 is formed in the thickness of the insulating support 4 that forms the intermediate layer 4 extending parallel to the lower layer 3.

[0061] The microfluidic electrochemical device 100 includes a microfluidic channel 11, a first end of which is connected to an inlet 6 and a second end of which is connected to an outlet 22. Thus, sweat flow 9 from the subject's skin 2 is conveyed to the microfluidic channel 11, which then conveys the sweat from the inlet 6 to the outlet 22 by capillary action.

[0062] The microfluidic channel 11 is provided with an electrochemical cell 14, which will be described later, and is shown in Figure 7 or 8. The electrochemical cell 14 is disposed on the inner surface of the upper layer 10 and blocks the microfluidic channel 11 from above so as to enter the internal space of the microfluidic channel 11.

[0063] In terms of dimensions, the diameter of the inlet 6 is several millimeters, the length of the microfluidic channel 11 is in the range of 0.5 cm to 5 cm, the width is in the range of 20 μm to 1,000 μm, the thickness of the intermediate layer 4 is in the range of 10 μm to 500 μm, the width of each layer 3, 4, 10 of the multilayer structure is in the range of 1 cm to 5 cm, and the length of each layer 3, 4, 10 is in the range of 2 cm to 10 cm.

[0064] For example, the diameter of the inlet 6 is 5 mm, the length of the microfluidic channel 11 is 3 cm and the width is 200 μm, the thickness of the intermediate layer 4 is 150 μm, and the width and length of each layer 3, 4, 10 of the multilayer structure are 3 cm and 9 cm, respectively.

[0065] 5 and 6, in the second embodiment, the device 1 has a main channel 23, which is divided into one or more parallel microfluidic channels in the direction of sweat flow 9. These microfluidic channels are formed in the thickness of the insulating support member 6 and separated by partitions 12. In this example, the microfluidic channels are parallelepiped-shaped. In this way, each microfluidic channel 11a, 11b, and 11c is separated from the other microfluidic channels 11a, 11b, and 11c, respectively, and sweat can circulate independently within each of these microfluidic channels 11a, 11b, and 11c. The number of microfluidic channels may be greater or less than that shown in FIGS. 5 and 6.

[0066] In terms of dimensions, the microfluidic channels 11a, 11b, and 11c preferably have a height in the range of 10 μm to 500 μm, a width in the range of 20 μm to 1,000 μm, and a length in the range of 0.5 cm to 5 cm. a ,S b ,S c is constant. For simplicity, and without loss of generality, we assume that the cross sections of the microfluidic channels 11a, 11b, and 11c have the same area S. That is, S a =S b =S c Assume that =S.

[0067] Sweat secreted by the subject 2 in the investigation zone 8 is collected by the portion of the collecting element that contacts the subject's skin 2 and then transported by capillary action to the main channel 23, where the sweat circulates independently through the microfluidic channels 11a, 11b, and 11c of the microfluidic electrochemical device 100. Arrows 13 indicate the direction of sweat flow within the microfluidic channels 11a, 11b, and 11c. Each microfluidic channel 11a, 11b, and 11c is provided with an electrochemical cell 14a, 14b, or 14c, respectively, as shown in FIG. 6 and in detail in FIG. 7 or 8. Preferably, the microfluidic channels 11a, 11b, and 11c are connected to an outlet reservoir that is connected to an outlet 22. The outlet reservoir retains the sweat to prevent it from contacting the skin 2 again.

[0068] Referring to FIG. 7, the electrochemical cells 14, 14a, 14b, and 14c are based on a four-electrode configuration. More specifically, the electrochemical cells 14, 14a, 14b, and 14c include a pair of independent working electrodes WE1 and WE2, a counter electrode CE, and a reference electrode REF, which are arranged in the microfluidic channels 11, 11a, 11b, and 11c. The electrodes WE1, WE2, CE, and REF are parallel microelectrodes fabricated in the form of microelectrode strips perpendicular to the direction of sweat flow in the microfluidic channels 11, 11a, 11b, and 11c, for example, by chemical vapor deposition (CVD) and / or lithography. The length of the microelectrode strips therefore corresponds to the width of the microfluidic channels 11, 11a, 11b, and 11c.

[0069] The working electrodes WE1 and WE2 are fabricated in the form of microstrips made of platinum or platinized platinum, also known as platinum black, and have a thickness on the nanometer level, for example, several tens of nanometers to a hundred nanometers, typically 200 nm. The working electrodes WE1 and WE2 are spaced apart by an interelectrode distance L, L in the direction of sweat flow in the microfluidic channels 11, 11a, 11b, and 11c. a ,Lb ,L c As explained below, the electrode distances L and L a ,L b ,L c varies depending on the microfluidic flow channel 11, 11a, 11b, 11c considered. The first working electrode is designated by the symbol WE1 and the second working electrode is designated by the symbol WE2. By convention, the first working electrode WE1 is located upstream of the second working electrode WE2 with respect to the direction of sweat flow of the analyte 2 in the microfluidic flow channel 11, 11a, 11b, 11c.

[0070] The reference electrode REF is made, for example, in the form of a strip of Ag / AgCl reference microelectrode.

[0071] The counter electrode CE is manufactured, for example, in the form of a platinum microstrip, which may be platinum-plated or non-platinized. The thickness of the counter electrode CE is, for example, on the order of several tens to several hundreds of nanometers, typically 100 nm. The counter electrode CE is positioned downstream of the pair of working electrodes WE1 and WE2, and thus downstream of the reference electrode REF, so that chemical species generated at its surface do not inhibit the working electrodes WE1 and WE2 or the reference electrode REF. Advantageously, the surface of the counter electrode CE is two to three times larger than that of the other electrodes.

[0072] Advantageously, all the microelectrodes made in the form of microstrips described above are deposited on a sub-nanometer adhesion layer (not shown) to ensure a good adhesion of the microstrips onto the insulating support 4. This is made, for example, of titanium or chromium, depending on the nature of the insulating support 4.

[0073] The microfluidic electrochemical device 100 also includes an electrochemical amperometric measurement system 15. Each of the electrodes WE1, WE2, CE, and REF is connected to the electrochemical amperometric measurement system 15 via an electrical contact (not shown) that is electrically isolated from the subject's sweat.

[0074] The electrochemical amperometric measurement system 15 includes, for example, a potentiostat or multipotentiostat (not shown) configured to control one or all or a portion of the electrochemical cells 14 a, 14 b, and 14 c. More specifically, the electrochemical amperometric measurement system 15 biases a first working electrode WE1 of the electrochemical cells 14 a, 14 b, and 14 c at a first electrode potential E1, biases a second working electrode WE2 of the electrochemical cells 14 a, 14 b, and 14 c at a second working electrode E2, and supplies water HO (l) or water H2O (l) The reaction of the redox couple species related to the sweat, especially the dioxygen O 2(aq) This also causes (Example 3).

[0075] The average volumetric flow rate Q of sweat circulating through the microfluidic channel 11, 11a, 11b, or 11c is determined based on the principle of the "time of flight" technique, i.e., the time at which electroactive species detected by amperometry are absorbed by the first working electrode WE2 and the second working electrode WE3 relative to the inter-electrode distances L, L. a ,L b ,L c and the volume of the microfluidic channels 11, 11a, 11b, 11c defined by a plane perpendicular to the plane on which the working electrodes WE1, WE2 are crimped and located at their respective most upstream limits.

[0076] In the following three examples, working electrodes WE1 and WE2 are biased according to the methods shown in FIGS. 9 and 10 (Example 1), FIGS. 11 and 12 (Example 2), and FIGS. 13 and 14 (Example 3), respectively. These methods include multiple steps, which are described in more detail for each specific example below. Graphs 101, 121, and 141 show the first electrode potential E1 applied to the first working electrode WE1 as a function of time t. Graphs 102, 122, and 142 show the second electrode potential E2 applied to the second working electrode WE2 as a function of time t. When the first and second electrode potentials E1 and E2 assume a value of "0" in graphs 101, 102, 121, 122, 141, and 142, this corresponds to disconnecting (open circuiting) the working electrode WE1 or WE2, or to considering a potential close to or equal to the equilibrium potential. Graphs 103, 123, and 143 show the magnitude of the faradaic current measured at the first working electrode WE1 as a function of time t. Finally, graphs 104, 124, and 144 show the magnitude of the faradaic current measured at the second working electrode WE2 as a function of time t.

[0077] The values of the electrode potentials E1 and E2 given as examples are given in units of volts relative to the standard hydrogen electrode (V / SHE). By convention, anodic magnitudes of faradaic currents are taken to be positive values and cathodic magnitudes of faradaic currents are taken to be negative values.

[0078] <Example 1> In a first example, referring to FIG. 9, the first working electrode WE1 is biased at a first electrode potential E1, typically 1.6 V / SHE, and water HO (l) is oxidized to dioxygen O according to the following redox half reaction: 2(aq) The difference in electrode potential between the first working electrode WE1 and the counter electrode CE is set so that the difference in electrode potential between the first working electrode WE1 and the counter electrode CE can be set to . 6H2O (l) →O 2(aq) +4H3O + (aq) +4e -

[0079] Correspondingly, the second working electrode WE2 is biased at a second electrode potential E2, typically -0.3V / SHE, and oxygen O generated on the surface of the working electrode WE1 according to the following redox half-reaction formula 2(aq) , that is, the oxygen O dissolved in sweat 2(aq) is reduced to water H2O (l) . The difference in electrode potential between the second working electrode WE2 and the counter electrode CE is set so that this occurs. O 2(aq) + 4H3O + (aq) + 4e - → 6H2O (l)

[0080] Referring to FIG. 10, the method of biasing the first and second working electrodes WE1 and WE2 includes two consecutive steps over time t.

[0081] In the first step, before time t0 (i.e., t < t0), the first electrode potential E1 applied to the first working electrode WE1 can be set near the initial equilibrium potential, or the first working electrode WE1 can be disconnected. The latter assumption is shown in graph 101, in which case the first electrode potential E1 conventionally takes a value of zero "0". As shown in graph 103, the detected anode intensity i ox is zero.

[0082] At the same time, the second electrode potential E2 applied to the second working electrode WE2 shown in graph 102 is set lower than the initial equilibrium potential and to a value sufficient to reduce the dissolved oxygen O 2(aq) . The cathode intensity i red is proportional to the concentration of dioxygen O 2(aq) dissolved in sweat, and if this initial concentration is zero, the cathode intensity i red is zero.

[0083] In the second step starting from time t0, the first electrode potential E1 applied to the first working electrode WE1 shown in graph 101 is fixed at the oxidation wave of water H2O (l) , and dioxygen O2(aq) In other words, the amount of dioxygen O near the surface of the first working electrode WE1 begins to increase. 2(aq) The total concentration of dioxygen (O2) dissolved in sweat 2(aq) In this way, the concentration of oxygen O generated on the surface of the first working electrode WE1 becomes much higher than that of the first working electrode WE2. 2(aq) The anode strength i is a quantity that represents the amount of ox is set by the first electrode potential E1 applied to the first working electrode WE1. ox becomes constant over time as soon as the capacitive current associated with the potential jump is cancelled, since the reactant is water HO (l) Therefore, the redox reaction envisaged at the first working electrode WE1 is not limited by transport of substances. The capacitive currents associated with potential switching are not shown in the figures, which only consider faradaic currents.

[0084] As soon as the first working electrode WE1 is biased at time t0, dissolved oxygen O 2(aq) The anodic intensity i measured at the first working electrode WE1 is ox is water H2O (l) In graph 103, the anodic strength i ox The increase in dioxygen O is shown schematically by a step function or Heaviside function. 2(aq) The concentration gradient of forms a convection-driven concentration front downstream of the first working electrode WE1 under the influence of sweat flow.

[0085] At the same time, the second working electrode WE2 remains biased at a constant second electrode potential E2. 2(aq) is water H2O (l) The cathodic intensity of the faradaic current i produced by the reduction of red In this way, at time t0+Δt, the amount of dioxygen O produced on the surface of the first working electrode WE1 is 2(aq) As the concentration front of oxygen passes over the surface of the second working electrode WE2, oxygen O 2(aq)is water H2O (l) The detected cathodic intensity i red (in relative terms), which is shown in graph 104. The duration Δt is the time it takes for the dioxygen O2 generated at the first working electrode WE1 to decrease under the influence of sweat flowing through the microfluidic channel 11, 11a, 11b or 11c at a flow rate V. 2(aq) It corresponds to the time required for the front to travel to the second working electrode WE2.

[0086] The second step ends at a time t1 after time t0, from which the first working electrode WE1 is again biased or disconnected at a first electrode potential E1 close to the initial equilibrium potential, as shown in graph 101. The first working electrode WE1 is then rebiased so that the method can be repeated as many times as necessary to determine the average volumetric flow rate Q at successive times that are more or less close to each other.

[0087] The method described above is simple and easy to industrialize, since it does not require any moving parts and does not require any assumptions about the hydrodynamic state of sweat flow in the microfluidic channel. This solution is not related in any way to determining the concentration of chemical species contained in or produced in sweat, but only to the response time Δt between the amperometric signals of the pair of working electrodes WE1 and WE2. In particular, the concentration of water HO (l) Oxidation reaction of and dioxygen O 2(aq) By selecting the reduction reaction, the amplitude of the detected amperometric signal can be directed to each working electrode WE1, WE2, thereby maintaining a sufficient signal-to-noise ratio so that changes in the amperometric signal can be easily detected.

[0088] <Example 2> In a second example, referring to FIG. 11, the first working electrode WE1 is biased at a first electrode potential E1, typically −0.8 V / SHE, and water HO (l) is reduced to dihydrogen H according to the following redox half reaction: 2(aq) The difference in electrode potential between the first working electrode WE1 and the counter electrode CE is set so that the difference in electrode potential between the first working electrode WE1 and the counter electrode CE can be set to . 2H2O (l) +2e - →H 2(aq) +2OH - (aq)

[0089] Correspondingly, the electrode potential difference between the second working electrode WE2 and the counter electrode CE is set so that the second working electrode WE2 is biased at a second electrode potential E2 equal to the first electrode potential E1. Thus, similar to the first working electrode WE1, the second working electrode WE2 is configured to reduce water H2O in sweat (l) to dihydrogen H 2(aq) .

[0090] Referring to FIG. 12, the method of applying a bias to the first and second working electrodes WE1 and WE2 includes two consecutive steps over time t.

[0091] In the first step, before time t0, i.e., at t < t0, the first electrode potential E1 applied to the first working electrode WE1 can be set near the initial equilibrium potential, or the first working electrode WE1 can be disconnected. The latter assumption is shown in graph 121, in which the first electrode potential E1 conventionally takes a value of zero "0" so that the detected cathode intensity i red becomes zero as shown in graph 123.

[0092] At the same time, the second electrode potential E2 applied to the second working electrode WE2 shown in graph 112 is lower than the initial equilibrium potential, whereby water in sweat is reduced to dihydrogen H 2(aq) . The cathode intensity i red is constant as shown in graph 124.

[0093] In the second step starting from time t0, since the first electrode potential E1 applied to the first working electrode WE1 shown in graph 111 is lower than the initial equilibrium potential, the reduction of water in sweat to dihydrogen H 2(aq) is started. At the first working electrode WE1, water H2O (l)When the pH is reduced, the pH increases, and the cathodic intensity i detected at the first working electrode WE1 red In graph 123, the cathode strength i red The increase in the sweat concentration is shown schematically by a step function or a Heaviside function. The above-mentioned portion of the hydrolyzed sweat is transported by convection downstream of the first working electrode WE1 under the influence of the flow.

[0094] At the same time, the second working electrode WE2 remains biased at a constant second electrode potential E2. The second working electrode WE2 detects the water in the sweat converting into dihydrogen H 2(aq) The cathodic intensity of the faradaic current i produced by the reduction of red is continuously recorded. In this way, at time t0 + Δt, when the partially hydrolyzed sweat flow passes over the surface of the second working electrode WE2, the detected cathodic intensity i red increases (relatively), which is shown in graph 114, because the hydronium ion HO + (aq) The duration Δt is the time it takes for the hydronium ions generated at the first working electrode WE1 to deplete HO under the influence of sweat flowing through the microfluidic channel 11, 11a, 11b, or 11c at a flow rate V. + (aq) This corresponds to the time required for the sweat flow front to travel to the second working electrode WE2.

[0095] The volume of sweat whose pH has increased due to the action of the first electrode advances from the first working electrode WE1 to the second working electrode WE2 under the influence of the sweat flowing at a flow rate V through the microfluidic channel 11, 11a, 11b or 11c.

[0096] The second step ends at time t1 after time t0, at which point the first working electrode WE1 is either rebiased at a first electrode potential E1 close to the initial equilibrium potential or disconnected, as shown in graph 121. The first working electrode WE1 is then rebiased so that the method can be repeated as many times as necessary to determine the average volumetric flow rate Q at closely successive times.

[0097] The method described above is simple and easy to industrialize, since it does not require any moving parts or assumptions about the hydrodynamic state. This solution is in no way related to determining the concentration of chemical species contained in or produced in sweat, but only to the response time Δt between fluctuations in the amperometric signal of the pair of working electrodes WE1 and WE2.

[0098] <Example 3> In a third example, referring to FIG. 13, the first working electrode WE1 is biased at a first electrode potential E1, typically −0.3 V / SHE, and oxygen O 2 initially dissolved in the aqueous solution to be tested, if any, is detected. 2(aq) Only water HO is reduced according to the following redox half reaction: (l) The difference in electrode potential between the first working electrode WE1 and the counter electrode CE is set so that the difference in electrode potential between the first working electrode WE1 and the counter electrode CE can be set to . O 2(aq) +4H3O + (aq) +4e - →6H2O (l)

[0099] Correspondingly, the electrode potential difference between the second working electrode WE2 and the counter electrode CE is set so that the second working electrode WE2 is biased at a second electrode potential E2 equal to the first electrode potential E1. In this way, the second working electrode WE2, like the first working electrode WE1, can absorb oxygen O dissolved in sweat. 2(aq) The fraction of water H2O that was not reduced at the first working electrode WE1 was reduced. (l) It is configured to be.

[0100] Referring to FIG. 14, the method of applying a bias to the first and second working electrodes WE1 and WE2 includes two consecutive steps over time t.

[0101] In the first step, before time t0, that is, at t < t0, the first electrode potential E1 applied to the first working electrode WE1 can be set near the initial equilibrium potential, or the first working electrode WE1 can be disconnected. The latter assumption is shown in graph 141, in which the first electrode potential E1 conventionally takes a value of zero "0" so that the detected cathode intensity i red becomes zero as shown in graph 143.

[0102] At the same time, the second electrode potential E2 applied to the second working electrode WE2 shown in graph 142 is lower than the initial equilibrium potential, whereby dioxygen O 2(aq) is reduced to water H2O (l) . As shown in graph 144, the cathode intensity i red is constant because it is proportional to the concentration of dioxygen O 2(aq) dissolved in the sweat.

[0103] In the second step starting from time t0, the first electrode potential E1 applied to the first working electrode WE1 shown in graph 141 is lower than the initial equilibrium potential, so that all or part of the reduction of dioxygen O 2(aq) dissolved in the sweat is started. As a result of the reduction of oxygen O 2(aq) to water H2O (l) , the cathode intensity i red detected at the first working electrode WE1 decreases (relative value). In graph 143, the increase and decrease of the cathode intensity i red are schematically shown by a step function or a Heaviside function. The hydrolyzed part of the dissolved oxygen depletion O 2(aq) in the sweat is convected downstream of the first working electrode WE1 under the influence of the flow.

[0104] At the same time, the second working electrode WE2 remains biased at a constant second electrode potential E2. 2(aq) is water H2O (l) The cathodic intensity of the faradaic current i produced by the reduction of red is continuously recorded. In this way, at time t0 + Δt, the dioxygen depletion O 2(aq) As the sweat stream passes over the surface of the second working electrode WE2, the detected cathodic intensity i red increases (relatively), i.e. approaches zero, as shown in graph 144. This is because the amount of dioxygen dissolved in sweat, O 2(aq) The duration Δt is the time it takes for the dissolved dioxygen depletion O 2(aq) This corresponds to the time required for the sweat flow to travel from the first working electrode WE1 to the second working electrode WE2.

[0105] The second step ends at a time t1 after time t0, from which the first working electrode WE1 is again biased or disconnected at a first electrode potential E1 close to the initial equilibrium potential, as shown in graph 141. The first working electrode WE1 is then rebiased so that the method can be repeated as many times as necessary to determine the average volumetric flow rate Q at successive times that are more or less close to each other.

[0106] The method described above is simple and easy to industrialize, since it does not require any moving parts or assumptions about the hydrodynamic state. This solution is in no way related to determining the concentration of chemical species contained in or produced in sweat, but only to the response time Δt between fluctuations in the amperometric signal of the pair of working electrodes WE1 and WE2.

[0107] In the above three examples, the flow velocity V and volumetric flow rate Q of sweat flowing through the rectangular parallelepiped microfluidic channel 11, 11a, 11b, or 11c with a constant cross-sectional area S in the flow direction 13 are determined by the inter-electrode distances L, L separating the working electrodes WE1 and WE2. a ,L b ,L c and the duration Δt characteristic of the delay in the response of the second working electrode WE2 relative to the instantaneous response of the first working electrode WE1, monitored by chronoamperometry. Under the conditions described below, the mean linear flow velocity V and mean volumetric flow rate Q of the sweat flow circulating in a microfluidic channel, such as the microfluidic channel denoted by reference numeral 11, can be estimated according to the following formulas: where the inter-electrode distance corresponding to the microfluidic channel 11 is denoted by reference numeral L. V=L / Δt Q=S×V=L×S / Δt Under the same conditions, the above formulas are calculated by dividing the inter-electrode distance L by the inter-electrode distance L a ,L b ,L c This substitution is effective in each of the corresponding microfluidic channels 11a, 11b, and 11c.

[0108] In a contemplated dynamic application, when monitoring a subject's physiological condition over time, the device 1 may usefully determine a quantitative sweat parameter of the subject by measuring the sweat volumetric flow rate Q at closely successive time points that correspond to an expected sweat rate, e.g., once per minute. The temporal variation of the sweat volumetric flow rate Q can then be integrated to determine the total sweat flow rate secreted by the subject over a specific time range t.

[0109] The quantitative sweating parameter may be a sweating rate determined based on the total volume of sweat secreted by the subject over a specific time range t relative to the surface area of the investigation zone 8.

[0110] The interelectrode distance L, L separating the working electrodes WE1 and WE2 a ,L b ,L c is selected to be small enough to cause negligible changes in the subject's physiological response over the duration Δt, and large enough to enable uncoupled movement patterns of the working electrodes WE1 and WE2 in the or each microfluidic channel 11, 11a, 11b, 11c where the volumetric flow rate Q is measured.

[0111] In practice, depending on the average linear flow velocity V of sweat in the microfluidic channel 11, 11a, 11b, or 11c, the concentration gradient generated near the first working electrode by generating electroactive species (Example 1) or depleting electroactive species already contained in sweat (Examples 2 and 3) is proportional to the inter-electrode distance L, L a ,L b ,L c After being transported across the microfluidic channel 11, 11a, 11b, or 11c, the sweat concentration gradient may or may not be uniform across the height of the microfluidic channel 11, 11a, 11b, or 11c. In particular, under a given linear sweat flow rate V, the operation of the two working electrodes WE1 and WE2 is coupled when the concentration gradient does not have time to diffuse across the height of the microfluidic channel 11a, 11b, or 11c before reaching the second working electrode WE2. This coupled pattern limits the time resolution of the amperometric signal, and such limitation hinders the measurement of the volumetric flow rate Q of sweat circulating through the microfluidic channel 11a, 11b, or 11c. Such a hindrance is due to the inter-electrode distance L, L. a ,L b ,L c This can be easily avoided by adjusting the relative values of t and t to the expected value of the mean linear flow velocity V.

[0112] In the first embodiment shown in FIG. 6, different inter-electrode distances L a ,L b ,L cMultiple pairs of first and second working electrodes WE1 and WE2 separated by an inter-electrode distance L may be used in separate parallel microfluidic channels 11a, 11b, and 11c. Preferably, the inter-electrode distance L separating the working electrodes WE1 and WE2 is a ,L b ,L c varies depending on the corresponding microfluidic channel 11a, 11b, or 11c, for example, L a <L b <L c It differs so that

[0113] In the second embodiment shown in FIG. 8, as a variant, an array of second working electrodes can be provided in the same microfluidic channel 11, 11a, 11b or 11c, which in this example is the first second working electrode WE2. (1) and a second working electrode WE2 (2) In some embodiments not shown, the array of second working electrodes can include more than two second working electrodes. The remainder of this description will be limited to the discussion of the array of second working electrodes located in the microfluidic channel designated 11. Such an array could also be located in microfluidic channel 11a, 11b, or 11c.

[0114] In the microfluidic channel 11, each second working electrode WE2 (1) ,WE2 (2) are different inter-electrode distances L from the first working electrode WE1, respectively. (1) , L (2) The working electrodes WE1 and WE2 are arranged (1) , WE2 (2) is electronically switchable. The duration t1-t0 is electronically adjusted by feeding back the average linear flow velocity value V measured at a number of previous measurement points.

[0115] In this way, the volumetric flow rate Q can be calculated over a wide range of values, because the distance between the electrodes L a ,L b ,L c,L (1) ,L (2) Advantageously, the inter-electrode distance L can be adjusted to 0.5 μm, since it is possible to measure the volume flow rate Q in each microfluidic channel 11, 11a, 11b or 11c or in several of these microfluidic channels while retaining only measurements of the volume flow rate Q that are consistent with a ,L b ,L c ,L (1) ,L (2) is on the order of millimeters.

[0116] The above method for measuring sweat volumetric flow rate Q can be performed automatically using an electronic processing device 16, which is preferably integrated into the device 1.

[0117] An embodiment of an electronic processing device 16 that can be incorporated into the device 1 will now be described with reference to Figure 15. This is for example in the form of an electronic board 17.

[0118] 5 and 6, the electrochemical cells 14a, 14b, 14c are connected to an analog-to-digital converter 18, which itself powers a processor 19. The processor 19 is programmed to implement, for example, the method for measuring the sweat volumetric flow rate Q described above.

[0119] In the embodiment shown in FIG. 8, a first working electrode WE1 and a plurality of second working electrodes WE2 (1) , WE2 (2) and the electrode distance L (1) and L (2) are arranged in the same microfluidic channel 11, but in this embodiment, the first working electrode WE1 and the second working electrode WE2 (1) ,WE2 (2)Each pair, consisting of one of the electrodes and one of the electrodes, constitutes an electrochemical cell 14, which is itself connected to an analog-to-digital converter 18 that supplies power to a processor 19. The processor 19 is programmed, for example, to implement the method for measuring the sweat volumetric flow rate Q described above.

[0120] The electronic processing device 16 is powered by an energy source 20, for example a battery. A wired or wireless communication module 21 may be provided for transmitting the measurements of the sweat volume flow rate Q to a storage or post-processing device.

[0121] The electronic processing device 16 may optionally include other functional modules, such as a gyroscope and / or accelerometer module for detecting the orientation and movement of the subject 2 and quantifying its activity level, and / or a temperature sensor for measuring the temperature of the epidermis of the subject 2. Indeed, due to the correlation between temperature and sweat rate, it is valuable to know the skin temperature.

[0122] Some elements of device 1, particularly electronic processing unit 16, may be implemented in various forms using hardware and / or software components and may be provided in a unitary or distributed form. Possible hardware components include application specific integrated circuits (ASICs) and field programmable gate arrays (FPGAs). Software components may be written in various programming languages, such as C, C++, Java, or VHDL. This list is not intended to be limiting.

[0123] Although the present invention has been described with reference to some specific embodiments, it is clear that the invention is not limited thereto, but includes all technical equivalents of the described means and combinations thereof, when falling within the scope of the invention.

[0124] Use of the verbs "to comprise" and "to have" and their conjugations does not exclude the presence of elements or steps other than those stated in a claim.

[0125] In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim.

Claims

1. A microfluidic electrochemical device (100) for measuring the volumetric flow rate (Q) of a solvent-containing fluid, At least one microfluidic channel (11, 11a, 11b, 11c) configured to allow the fluid to flow in the flow direction (13), Disposed in the at least one microfluidic flow path (11, 11a, 11b, 11c), a first working electrode (WE １ ), at least one second (WE ２ , WE ２ （１） , WE ２ （２） ), at least one counter electrode (CE), and at least one reference electrode (REF), and at least one electrochemical cell (14, 14a, 14b, 14c), wherein the at least one second working electrode (WE ２ , WE ２ （１） , WE ２ （２） ) is separated from the first working electrode (WE １ ) by an electrode spacing (L ａ , L ｂ , L ｃ , L （１） , L （２） ) in the flow direction (13), and the electrochemical cell (14, 14a, 14b, 14c) and, The first working electrode (WE １ ) the first electrode potential (E １ ) is biased with the second working electrode (WE ２ , WE ２ （１） , WE ２ （２） ) at the second electrode potential (E ２ An electrochemical amperometry measurement system (15) that generates an amperometry signal by applying a bias to the first working electrode and the second working electrode, respectively, by an oxidation or reduction reaction of the solvent, or by an oxidation or reduction reaction of the solvent with at least one chemical species that forms an oxidation-reduction pair with the solvent, It is equipped with, The electrochemical amperometry measurement system (15) measures the distance between electrodes (L ａ , L ｂ , L ｃ , L （１） , L （２） ) and the first working electrode (WE １ The fluctuations in the amperometry signal caused by the second working electrode (WE ２ , WE ２ （１） , WE ２ （２） The system is configured to determine the volumetric flow rate (Q) of the fluid in the microfluidic channels (11, 11a, 11b, 11c) based on the time delay (Δt) between the fluctuations in the amperometric signal caused by the amperometry signal and the microfluidic channel (11, 11a, 11b, 11c). A microfluidic electrochemical device (100) characterized by the following features.

2. The solvent is water H ２ It is O. The microfluidic electrochemical device (100) according to claim 1.

3. The fluid is the sweat of a human or animal subject. The microfluidic electrochemical device (100) according to claim 2.

4. The first electrode potential (E １ ) is water H ２ Oxidation of O to dioxygen O ２ It can be done, The second electrode potential (E ２ ) is the water H that is produced. ２ The dioxygen O dissolved in O ２ Reduce to water H ２ It can be set to O. The microfluidic electrochemical device (100) according to claim 2 or 3.

5. The first electrode potential (E １ ) is water H ２ O is reduced to dihydrogen H ２ It can be done, The second electrode potential (E ２ ) is water H ２ O is reduced to dihydrogen H ２ It can be done The microfluidic electrochemical device (100) according to claim 2 or 3.

6. The first electrode potential (E １ ) is water H ２ The dioxygen O dissolved in O ２ Reduce to water H ２ It can be set to O, The second electrode potential (E ２ ) is water H ２ The dioxygen O dissolved in O ２ Reduce to water H ２ It can be set to O. The microfluidic electrochemical device (100) according to claim 2 or 3.

7. The electrochemical amperometry measurement system (15) is In the first step, the first working electrode (WE １ ) the first electrode potential (E １ ) is biased with the second working electrode (WE ２ ) at the second electrode potential (E ２ ) apply bias, In the second step, the first working electrode (WE １ ) disconnect, or the first electrode potential (E １ Set the potential to near or equal to the zero current equilibrium potential. A microfluidic electrochemical device (100) according to any one of claims 1 to 3.

8. It is further equipped with an insulating support part (4), The at least one microfluidic channel (11, 11a, 11b, 11c) is formed in the insulating support portion (4), The first working electrode (WE １ ) and the at least one second working electrode (WE ２ , WE ２ （１） , WE ２ （２） ) is formed by a platinum or platinum black metal deposit provided on the insulating support portion (4), A microfluidic electrochemical device (100) according to any one of claims 1 to 3.

9. The counter electrode (CE) is in the flow direction (13) the working electrode (WE) １ , WE ２ , WE ２ （１） , WE ２ （２） It is located downstream from ) The reference electrode (REF) is in the flow direction (13) and the working electrode (WE １ , WE ２ , WE ２ （１） , WE ２ （２） Located upstream of ) A microfluidic electrochemical device (100) according to any one of claims 1 to 3.

10. It further comprises a first microfluidic channel (11a) and a second microfluidic channel (11b), The first microfluidic channel (11a) is configured with the first electrochemical cell (14a), and the second microfluidic channel (11b) is configured with the second electrochemical cell (14b). The distance between electrodes (L) of the first electrochemical cell (14a) ａ ) is the distance between electrodes (L) of the second electrochemical cell (14b). ｂ ) is different from A microfluidic electrochemical device (100) according to any one of claims 1 to 3.

11. The at least one electrochemical cell (14a) has the second working electrode (WE ２ （１） , WE ２ （２） It has two of these, The second working electrode (WE ２ （１） , WE ２ （２） ) is separated from the first working electrode (WE １ ) by a first electrode distance (L （１） ) and a second electrode distance (L ａ （１） ), which is different from the first electrode distance (L （２） ), respectively. A microfluidic electrochemical device (100) according to any one of claims 1 to 3.

12. The electrochemical amperometry measurement system (15) is configured to determine the volumetric flow rate (Q) depending on the cross-sectional area of ​​the microfluidic flow channels (11, 11a, 11b, 11c) in the flow direction (13). A microfluidic electrochemical device (100) according to any one of claims 1 to 3.

13. A device (1) placed in an epidermal survey zone (8) of a human or animal subject for measuring quantitative sweat parameters of said subject, A structure for forming a microfluidic electrochemical device (100) according to any one of claims 1 to 3, comprising an inlet (6) defining the investigation zone (8), and a structure that allows at least one microfluidic channel (11, 11a, 11b, 11c) of the microfluidic electrochemical device (100) connected to the inlet (6) to be opened via perspiration from the epidermis, An electronic processing device (16) configured to determine quantitative sweating parameters of a human or animal subject based on the measurement results of the volumetric flow rate (Q) of sweat performed by the microfluidic electrochemical device (100), A device (1) characterized by having the following features.

14. The quantitative sweating parameter of the aforementioned human or animal subject is the sweating rate. The apparatus (1) according to claim 13.

15. The aforementioned structure is a multilayer structure having a lower layer (3) and at least one layer superimposed on the lower layer (3). The microfluidic electrochemical device (100) extends parallel to the lower layer (3), The lower layer (3) has the inlet (6), The apparatus (1) according to claim 13.

16. The multilayer structure further comprises an upper layer (10) and at least one intermediate layer (4) disposed between the lower layer (3) and the upper layer (10), The microfluidic electrochemical device (100) is formed within the thickness of the at least one intermediate layer (4), The apparatus (1) according to claim 15.

17. The upper layer (10) has an outlet (22) that penetrates the upper layer (10), The at least one microfluidic channel (11, 11a, 11b, 11c) is connected to the outlet (22). The apparatus (1) according to claim 16.

18. The first working electrode (WE １ ) and the at least one second working electrode (WE ２ , WE ２ （１） , WE ２ （２） ) and the at least one counter electrode (CE) and the at least one reference electrode (REF) are arranged on the inner surface of the upper layer (10) to block the at least one microfluidic channel (11, 11a, 11b, 11c) from above, and / or are arranged on the upper surface of the lower layer (3) to block the at least one microfluidic channel (11, 11a, 11b, 11c) from below. The apparatus (1) according to claim 16.

19. The device further comprises a communication device (21) that transmits one or more measurement signals generated by the microfluidic electrochemical device (100), The apparatus (1) according to claim 13.

20. The system further comprises a gyroscope module and / or at least one accelerometer for detecting the activity state of the human or animal subject, The apparatus (1) according to claim 13.

21. The system further includes a temperature sensor for measuring the temperature of the epidermis (2) of the human or animal subject. The apparatus (1) according to claim 13.

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