METHOD OF POSITIONING A SWEAT SENSOR DEVICE
20230134870 · 2023-05-04
Inventors
- EDUARD GERARD MARIE PELSSERS (LIMBURG, NL)
- Ron Martinus Laurentius van Lieshout (Geldrop, NL)
- Mark Thomas Johnson (Arendonk, BE)
- KIRAN HAMILTON DELLIMORE (UTRECHT, NL)
- Laurentia Johanna Huijbregts (Eindhoven, NL)
Cpc classification
International classification
A61B5/145
HUMAN NECESSITIES
Abstract
Provided is a method (400) of positioning a sweat sensor device (100), the method comprising: determining (410) a first skin location (i) of a mammalian subject, which first skin location (i) contains apocrine and eccrine sweat glands; determining (420) a second skin location (ii), adjacent to the first skin location (i), and having a different sweat gland composition than the first skin location, wherein at the second skin location (ii), predominantly eccrine sweat glands are present, and wherein the determining (410, 420) of the first (i) and second (it) skin locations is achieved by detecting differences between the first (i) and second (ii) skin locations; and positioning (430) the sweat sensor device (100) such that a first part of the sweat sensor device (100) is present on the first skin location (i), while a second part of the sweat sensor device (100) is present on the second skin location (ii).
Claims
1. A device for assisting in the positioning of a sweat sensor, the comprising: a processor configured to: detect a difference between: (a) a composition of sweat glands at a first skin location (i), wherein the composition of sweat glands at the first skin location (i) comprises apocrine and eccrine sweat glands, and (b) a composition of sweat glands at a second skin location (ii), wherein the second skin location (ii) is adjacent to a a first skin location (i), wherein the composition of sweat glands at the second skin location (ii) comprises eccrine sweat glands and is different from the composition of sweat glands at the first skin location (i), determine based on the difference of the composition of sweat glands at the first skin location (i) and the composition of sweat glands at the second skin location (ii), a correct position of the sweat sensor such that a first part of the sweat sensor is present on the first skin location (i), while a second part of the sweat sensor is present on the second skin location (ii).
2. The device according to claim 1, wherein the has a behavior or output that depends on whether the device is on top of the first skin location (i) and/or the second skin location (ii).
3. (canceled)
4. The device according to claim 1, wherein the processor is further configured to: receive a measurement of a first concentration (C.sub.a.sup.i) of a first analyte (a) in sweat excreted at the first skin location (i); receive a measurement at least one parameter of sweat excreted by eccrine sweat glands at the second skin location (ii); and determine a corrected concentration (C.sub.a) of the first analyte (a) in sweat from the first concentration (C.sub.a.sup.i) using said at least one parameter.
5. The device according to claim 1, wherein the device further comprises: a light source to illuminate a skin area; and a light detector which receives a reflection of light from the skin area.
6. The device according to claim 1, further comprising: a light source to illuminate a skin area; and a camera to produce an image of sweat on a skin.
7-8. (canceled)
9. The device according to claim 1, wherein the processor is further configured to: determine the presence of volatile organic compounds; determine the first skin location (i) in the event of detecting a first concentration of volatile organic compounds on the skin; and determine the second skin location (ii) in the event of detecting a second concentration of volatile organic compounds on the skin, where the first concentration of volatile organic compounds is greater than the second concentration of volatile organic compounds.
10. The device according to claim 1, wherein: the sweat sensor comprises: a first part which is covered with a first adherent material with hydrophilic properties and a second part, which is covered with any material adhering to skin, wherein the any material-adhering to the skin does not have hydrophilic properties; a first protective film which covers the first part, and leaves an opening of the first part of the sweat sensor uncovered; a second protective film which covers the second part of the sweat sensor.
11. The device according to claim 1, wherein: the sweat sensor comprise: a first part, which is covered with any material adhering to skin and does not have hydrophobic properties; a second part, which is covered with a second adherent material with hydrophobic properties; a first protective film which covers the first part of the sweat sensor; a second protective film which covers the second part of the sweat sensor, and leaving an opening of the second part of the sweat sensor uncovered.
12.-14. (canceled)
15. The device according to claim 1, wherein: the sweat sensor comprises a through hole, which reveals a skin of the mammalian subject; a transparent foil that covers the through hole and comprises a pattern reflecting a repetitive feature of a skin pattern of the first skin location (i) or the second skin location (ii).
16. (canceled)
17. The device according to claim 1, wherein: the sweat sensor comprises a through hole, which reveals a skin of the mammalian subject; and a transparent foil that covers the through hole and comprises a print of a repetitive pattern.
18. The device according to claim 1, wherein: the sweat sensor comprises a first part with a first sensor for detecting analytes present in apocrine sweat; and a second part with a second sensor for detecting analytes present in apocrine sweat.
19. The device according to claim 1, wherein: the sweat sensor comprises a first part, with a first sensor for detecting a periodic sweat rate; and a second part, with a second sensor adapted to detect a continuous sweat rate.
20. The device according to claim 5, wherein the processor is further configured to: determine the first skin location (i) in the event of the light detector detecting a first skin reflectivity; and determine the second skin location (i) in the event of the light detector detecting a second skin reflectivity, higher than the first skin reflectivity.
21. The device according to claim 6, wherein the processor is further configured to: determine the first skin location (i) where the image shows sweat originating from hair follicles; determine the second skin location (it) to be the skin area before the image shows sweat originating from hair follicles.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0047] Embodiments of the invention are described in more detail and by way of non-limiting examples with reference to the accompanying drawings, wherein:
[0048]
[0049]
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0050] It should be understood that the detailed description and specific examples, while indicating exemplary embodiments of the apparatus, systems and methods, are intended for purposes of illustration only and are not intended to limit the scope of the invention. These and other features, aspects, and advantages of the apparatus, systems and methods of the present invention will become better understood from the following description, appended claims, and accompanying drawings. It should be understood that the Figures are merely schematic and are not drawn to scale. It should also be understood that the same reference numerals are used throughout the Figures to indicate the same or similar parts.
[0051] EP 3622880 A1 provides a differential measuring method (and a related apparatus) for determining the corrected concentration (C.sub.a). The first skin location (i) may, for instance, have apocrine and eccrine glands. By measuring the first concentration (C.sub.a.sup.i) at the first skin location (i) of the first analyte (a) solely originating from apocrine glands (although at this stage diluted to an unknown degree by the eccrine glands at the the first skin location (i)) and measuring the parameter of sweat excreted by the eccrine glands at the second skin location (ii), the undiluted concentration of the first analyte (a) in the apocrine sweat may be determined unambiguously.
[0052] There is still a debate ongoing about the existence of a third gland type in the axilla: the apoeccrine gland. For present purposes, the first sweat gland type may, for instance, be regarded as including both the apocrine and apoeccrine glands. In this case, the second sweat gland type would correspond to the eccrine gland.
[0053]
[0054] Whilst not apparent from the plan view provided in
[0055] As shown in
[0056] The first sensor 104 may employ any suitable analyte concentration measurement principle, providing the first sensor 104 is able to measure the concentration of the first analyte (a). For example, colorimetry, electrical impedance, labelled antibodies, etc. may be used in the concentration measurement of the first analyte (a). A technique using labelled antibodies may, for instance, be used for protein concentration determination for specific proteins.
[0057] A second sensor 120, is provided in the apparatus 100 for measuring the at least one parameter of sweat excreted by the second sweat gland type at the second skin location ii, which has predominantly the second sweat gland type, and may not have the first sweat gland type.
[0058] In the embodiment shown in
[0059] The distance between the first and second sweat collection holes 106, 122 (132 in
[0060] When, for example, the first sweat sensor 104 and the second sweat sensor 120, are included in a single patch, the first and second sweat collection holes 106, 122 (132 in
[0061] Irrespective of whether the first and second sweat sensors 104, 120, 121 are included in a single patch, the first and second collection holes 106, 122 (132 in
[0062] The detector 120 may employ any suitable analyte concentration measurement principle, providing the detector 120 is able to measure the (third) concentration (C.sub.e.sup.ii) of the second analyte (e) at the second skin location ii. For example, colorimetry, electrical impedance, labelled antibodies, etc. may be used in the concentration measurement of the second analyte (e).
[0063] In the embodiment shown in
[0064] The third sensor 112 may employ any suitable analyte concentration measurement principle, providing the third sensor 112 is able to measure the (second) concentration (C.sub.e.sup.i) of the second analyte (e) at the first skin location i. For example, colorimetry, electrical impedance, labelled antibodies, etc. may be used in the concentration measurement of the second analyte (e).
[0065] An optional flow rate analyzer 128 may be included in the apparatus 100, as shown in
[0066] Any suitable detection principle may be used to measure the degree of filling of the thin channel 129. For example, the position of the meniscus in the thin channel 129 as a function of time may be determined from a suitable image. In this respect, the flow rate analyzer 128 may include a camera (not shown), and the apparatus 100 may, for instance, include a controller (not shown in
[0067] Whilst the flow rate analyzer 128 may be useful due to the dependency of concentrations of particular components on the sweat rate, this flow rate analyzer 128 is not essential in the context of the embodiment shown in
[0068] The first concentration (C.sub.e.sup.i) of the first analyte (a) at the first skin location i, as measured using the first sensor 104, may be expressed in terms of the dilution factor (D.sub.a.sup.i) and the corrected concentration (C.sub.a) in the following way:
C.sub.a.sup.i=C.sub.a.Math.D.sub.a.sup.i (Equation A).
[0069] Similarly, the second concentration (C.sub.e.sup.i) of the second analyte (e) at the first skin location i, as measured using the third sensor 112, may be expressed in terms of a further dilution factor (D.sub.e.sup.t), which quantifies dilution of the second analyte (e) by sweat excreted by the first sweat gland type at the first skin location i, and a corrected concentration of the second analyte (C.sub.e) in the following way:
C.sub.e.sup.i=C.sub.e.Math.D.sub.e.sup.i (Equation B).
[0070] The respective dilution factors D.sub.a.sup.i and D.sub.e.sup.i both have values between 0 and 1, and are related to each other by the following equation:
D.sub.a.sup.i+D.sub.e.sup.i=1 (Equation C).
[0071] Equation C reflects the mutual dilution of the respective sweats excreted by the first and second sweat gland types at the first skin location i. Combining Equations B and C gives:
[0072] It may be assumed that the undiluted concentration of the second analyte (e) in sweat of the second sweat gland type only at the first skin location i (i.e. correcting for the diluting effect of the sweat from the first sweat gland type) is equal, or at least very similar, to the concentration of the second analyte (e) at the second skin location ii, i.e.
C.sub.e=C.sub.e.sup.ii (Equation E);
[0073] This assumption holds particularly when the first and second locations i and ii are relatively close to each other, as may be the single patch 102 embodiments depicted in
[0074] Using Equation I, the second concentration (C.sub.e.sup.i) and the third concentration (C.sub.e.sup.ii) measured using the third sensor 112 and the detector 120 respectively, the dilution factor (D.sub.a.sup.i) may thus be determined. The corrected concentration (C.sub.a) may then be calculated from the dilution factor (D.sub.a.sup.i) and the first concentration (C.sub.a.sup.i) using Equation II (obtained by rearranging Equation A):
[0075] The units of the corrected concentration (C.sub.a), the first concentration (C.sub.a.sup.i), the second concentration (C.sub.e.sup.i) and the third concentration (C.sub.e.sup.ii) may all be, for instance, mol/L. Whilst not essential, measuring a total sweat flow rate using the flow rate analyzer 128 may permit assessment of the mean quantity of sweat that the subject is excreting, which may be used to refine the above calculations.
[0076] Whilst not shown in
[0077]
[0078] As shown in
[0079] The first sensor 104 may employ any suitable analyte concentration measurement principle providing the first sensor 104 is able to measure the concentration of the first analyte (a). For example, colorimetry, electrical impedance, or labelled antibodies, etc. may be used in the concentration measurement of the first analyte (a).
[0080] In the embodiment shown in
[0081] Any suitable detection principle may be used to measure the degree of filling of the thin channel 131. For example, the position of the meniscus in the thin channel 131 as a function of time may be determined from a suitable image. In this respect, the flow rate sensor 121 may include a camera (not shown), and the apparatus 100 may include a controller (not shown in
[0082] The inclusion of the flow rate sensor 121 in the apparatus 100 shown in
[0083] In other words, the measured flow rate of sweat from the second sweat gland type at the second skin location ii may be used to derive, via the dilution factor D.sub.a.sup.i, the real concentration of the first analyte (e.g. solely secreted by the apocrine gland) in the sweat excreted by the first sweat gland (e.g. apocrine sweat) at the first skin location i.
[0084] In an embodiment, determining the dilution factor (D.sub.a.sup.i) from the flow rate of sweat from the second sweat gland type at the second skin location ii comprises using a predetermined correlation between the flow rate and the dilution factor (D.sub.a.sup.i).
[0085] In order to attain such a predetermined correlation, a set of volunteers may, for instance, be used. Since these persons will have variable flow rates from glands of the second sweat gland type (e.g. eccrine glands), a correlation may be made of the dilution factor (D.sub.a.sup.i) as function of the flow rate of sweat from the second sweat gland type (e.g. eccrine glands) at the second skin location ii.
[0086] The apparatus 100 shown in
[0087] A correlation may thus be made between the dilution factor (D.sub.a.sup.i) and the flow rate of sweat from the second sweat gland type at the second skin location ii using the data from the volunteers. The resulting (predetermined) correlation may be, for example, in the form of a look-up table or graph, which may then be used determine the dilution factor (D.sub.a.sup.i) for a flow rate measured using the flow rate sensor 121 of the apparatus 100 shown in
[0088] Whilst use of such volunteer data may lead to lower accuracy for an individual, in certain clinical applications the accuracy may be sufficient. Moreover, in the embodiment shown in
[0089] At this point it is noted that the connections to and from the various sensors and detectors in the apparatuses 100 depicted in
[0090] Additional sensors may also be included in the apparatuses 100 shown in
[0091]
[0092] In step 220, at least one parameter is measured. The at least one parameter relates to sweat excreted by the second sweat gland type at a second skin location (ii) having predominantly the second sweat gland type and may not have the first sweat gland type. The at least one parameter is then used in step 260 to determine a dilution factor (D.sub.a.sup.i) which quantifies dilution of the first analyte by sweat excreted by the second sweat gland type at the first skin location (i). In step 270, the first concentration (C.sub.a.sup.i) is corrected using the dilution factor (D.sub.a.sup.i) so as to provide a corrected concentration (C.sub.a) of the first analyte (a).
[0093] Measuring 220 the at least one parameter may include measuring a flow rate of sweat from the second sweat gland type at the second skin location. This may be achieved, for instance, using the flow rate sensor 121 of the apparatus 100 shown in
[0094] Alternatively or additionally, the method 200 may further comprise measuring 230 a second concentration (C.sub.e.sup.i) of a second analyte (e) in sweat excreted by the second sweat gland type at the first skin location (i). This may, for instance, be achieved using the third sensor 112 of the apparatus 100 shown in
[0095] Using 260 the at least one parameter to determine the dilution factor (D.sub.a.sup.i) may comprise calculating the dilution factor (D.sub.a.sup.i) using the second concentration (C.sub.e.sup.i) and the third concentration (C.sub.e.sup.ii), e.g. using Equation I, as previously described. Determining 270 the corrected concentration (C.sub.a) from the first concentration (C.sub.a.sup.i) using the dilution factor (D.sub.a.sup.i) may use Equation II.
[0096] The method 200 may further include steps which enable anatomical variations in sweat gland density and sweat gland activation levels to be accounted for. Whilst the apparatuses 100 shown in
[0097] It may be a reasonable assumption that the average secretion rate per gland of the second sweat gland type (e.g. eccrine gland) is equal for nearby skin locations, e.g. spanned by the same patch 102. However, when the two skin locations (i) and (ii) are relatively far apart from each other, the average secretion rates of the second sweat gland type at the respective skin locations may usefully be taken into account.
[0098] It has been shown in previous studies, such as by Taylor and Machado-Moreira in “Regional variations in transepidermal water loss, eccrine sweat gland density, sweat secretion rates and electrolyte composition in resting and exercising humans” Extreme Physiology & Medicine 2013; 2:4 (referred to herein below simply as “Taylor”), that although sweating is synchronous across the entire body, eccrine glands from different regions of the body may discharge sweat at different rates. This may in turn imply that there may be a difference in biomarker concentration in the secreted sweat at different regions of the body, which is likely due to anatomical and physiological variations. According to Kondo et al. in “Regional difference in the effect of exercise intensity on thermoregulatory sweating and cutaneous vasodilation” Acta Physiologica Scandinavica 1998, 164:71-78, the level of sweat gland activation can vary between different skin regions with the sweat rate determined by both glandular recruitment and increases in flow rate.
[0099] The method 200 may therefore include the following additional steps, which account for regional variations in both the sweat gland density and the sweat gland secretion/discharge rate.
[0100] In step 240, a ratio (R.sub.act) between a first local activation level of glands of the second sweat gland type at the first skin location and a second local activation level of glands of the second sweat gland type at the second skin location may be calculated. In step 250, a value is generated using the at least one parameter and the ratio (R.sub.act). In this case, the value is used in step 260 to determine the dilution factor (D.sub.a.sup.i).
[0101] In an embodiment, the ratio (R.sub.act) is calculated using the following equation:
[0102] wherein SR.sub.i.sup.e and SR.sub.ii.sup.e are local sweat rates for the glands of the second sweat gland type at the first (i) and second (ii) skin locations respectively, and GD.sub.i.sup.e and GD.sub.ii.sup.e are local densities of the glands of the second sweat gland type at the first (i) and second (ii) skin locations respectively.
[0103] Equation III may be derived in the following way. The local sweat rate of the second sweat gland type at a given location (SR.sub.loc.sup.e) may be expressed as:
SR.sub.loc.sup.e=SR.sub.ag.sup.e.Math.N.sub.ag.sup.e (Equation F);
[0104] wherein SR.sub.ag.sup.e is the average sweat rate per activated gland of the second sweat gland type and N.sub.ag.sup.e is the average number of activated glands of the second sweat gland type.
N.sub.ag.sup.e=r.sub.loc.sup.e.Math.GD.sub.loc.sup.e.Math.A.sub.patch (Equation G);
[0105] wherein r.sub.loc.sup.e is the local ratio of active to inactive glands of the second sweat gland type, GD.sub.loc.sup.e is the local sweat gland density of glands of the second sweat gland type (which can, for instance, be derived from Taylor (see Table 3 of Taylor)) and A.sub.patch is the patch area (which is a known quantity).
[0106] The sweat rate is measured at two different skin locations (i) and (ii), yielding two different sweat rates, SR.sub.i.sup.e and SR.sub.ii.sup.e, respectively:
SR.sub.i.sup.e=SR.sub.ag;i.sup.e.Math.N.sub.ag;i.sup.e=SR.sub.ag;i.sup.e.Math.r.sub.i.sup.e.Math.GD.sub.i.sup.e.Math.A.sub.patch;i (Equation H);
SR.sub.ii.sup.e=AR.sub.ag;ii.sup.e.Math.=SR.sub.ag;ii.sup.e.Math.GD.sub.ii.sup.e.Math.A.sub.patch;ii (Equation H);
[0107] Rearranging Equations H and J gives:
[0108] Dividing Equation K by Equation L gives:
[0109] Assuming for simplicity that A.sub.patch; ii=A.sub.patch;i (i.e. the patch areas at the two skin locations are the same) and grouping SR.sub.ag;i.sup.e.Math.r.sub.i.sup.e/SR.sub.ag;ii.sup.e.Math.r.sub.ii.sup.e into a single term, R.sub.act, which captures the ratio of the local activation level of the sweat glands at the two sites, Equation M simplifies to:
[0110] If r.sub.i.sup.e is assumed to equal r.sub.ii.sup.e (i.e. the ratio of active to inactive sweat glands at the two sites is the same) then the ratio R.sub.act of sweat gland activity
at the first and second skin locations may be estimated.
[0111] The ratio R.sub.act may be used, for instance, to correct the measured (third) concentration of the second analyte (C.sub.e.sup.ii) at the second skin location (ii), for situations where the assumption that C.sub.e=C.sub.e.sup.ii (Equation E) may be less applicable, e.g. where the first and second patches are relatively far apart from each other. In such a scenario, the measured (third) concentration C.sub.e.sup.ii may be corrected by multiplying by R.sub.act. The resulting value may then be used in determining the dilution factor (D.sub.a.sup.i) using Equation I.
[0112] Alternatively, the ratio R.sub.act may be used to correct the measured (second) concentration of the second analyte (C.sub.e.sup.i) at the first skin location (i), in which case the (second) concentration C.sub.e.sup.i may be corrected by multiplying by
[0113] To implement step 240, the known (average) anatomical second sweat gland density (e.g. eccrine; see Table 3 provided in Taylor) may be used, together with a suitable correlation, e.g. a look-up table, of sweat gland discharge rate with the local sweat rate, the sweat gland density and the sweat gland activity. Such a correlation may be attained from volunteer testing.
[0114] In a non-limiting example, when the first and second patches are placed on the forehead and dorsal foot respectively, R.sub.act at the peak sweat rate would be, using Equation III:
[0115] The ratio 119/186 was derived from Table 3 provided in Taylor, and the number 2.5 for the ratio
has been derived from the graphs shown in
[0116] R.sub.act=1.6 implies that the sweat gland activity level at the forehead is 1.6 times that at the dorsal foot location. This may suggest that concentration of the second analyte at the forehead is therefore 1.6 times higher than at the dorsal foot.
[0117]
[0118] In this embodiment, the controller 150 uses the at least one parameter measured by the second sensor 120, 121 to determine the dilution factor (D.sub.a.sup.i). The controller 150 then determines the corrected concentration (C.sub.a) from the first concentration (C.sub.a.sup.i) using the dilution factor (D.sub.a.sup.i). In other words, the controller 150 is configured to implement steps 260 and 270 of the method 200 described above.
[0119] When the second sensor comprises the flow rate sensor 121, the controller 150 may determine the dilution factor (D.sub.a.sup.i) using the predetermined correlation between the flow rate and the dilution factor (D.sub.a.sup.i). The controller 150 may also be configured to detect the meniscus of the sweat in the thin channel 131 from a suitable image, i.e. during the process of determining the flow rate, as previously described.
[0120] Alternatively or additionally, when the apparatus 100 includes the third sensor 112 and the detector 120, the controller 150 may determine the dilution factor (D.sub.a.sup.i) using the second concentration (C.sub.e.sup.i) and the third concentration (C.sub.e.sup.ii), e.g. using Equation I. The corrected concentration (C.sub.a) may then be calculated from the dilution factor (D.sub.a.sup.i) and the first concentration (C.sub.a.sup.i) using Equation II, as previously described.
[0121] In an embodiment, the controller 150 is further configured to implement steps 240 and 250 of the method 200. In this respect, the controller 150 may calculate the ratio (R.sub.act) between the first local activation level of glands of the second sweat gland type at the first skin location and the second local activation level of glands of the second sweat gland type at the second skin location, e.g. using Equation III. The controller 150 may then generate the value using the at least one parameter and the ratio (R.sub.act), and determine the dilution factor (D.sub.a.sup.i) using the value.
[0122] As shown in
[0123]
[0124] The computer 500 includes, but is not limited to, PCs, workstations, laptops, PDAs, palm devices, servers, storages, and the like. Generally, in terms of hardware architecture, the computer 500 may include one or more processors 501, memory 502, and one or more I/O devices 503 that are communicatively coupled via a local interface (not shown). The local interface can be, for example but not limited to, one or more buses or other wired or wireless connections, as is known in the art. The local interface may have additional elements, such as controllers, buffers (caches), drivers, repeaters, and receivers, to enable communications. Further, the local interface may include address, control, and/or data connections to enable appropriate communications among the aforementioned components.
[0125] The processor 501 is a hardware device for executing software that can be stored in the memory 502. The processor 501 can be virtually any custom made or commercially available processor, a central processing unit (CPU), a digital signal processor (DSP), or an auxiliary processor among several processors associated with the computer 500, and the processor 501 may be a semiconductor based microprocessor (in the form of a microchip) or a microprocessor.
[0126] The memory 502 can include any one or combination of volatile memory elements (e.g., random access memory (RAM), such as dynamic random access memory (DRAM), static random access memory (SRAM), etc.) and non-volatile memory elements (e.g., ROM, erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), programmable read only memory (PROM), tape, compact disc read only memory (CD-ROM), disk, diskette, cartridge, cassette or the like, etc.). Moreover, the memory 502 may incorporate electronic, magnetic, optical, and/or other types of storage media. Note that the memory 502 can have a distributed architecture, where various components are situated remote from one another, but can be accessed by the processor 501.
[0127] The software in the memory 502 may include one or more separate programs, each of which comprises an ordered listing of executable instructions for implementing logical functions. The software in the memory 502 includes a suitable operating system (O/S) 504, compiler 505, source code 506, and one or more applications 507 in accordance with exemplary embodiments.
[0128] The application 507 comprises numerous functional components such as computational units, logic, functional units, processes, operations, virtual entities, and/or modules.
[0129] The operating system 504 controls the execution of computer programs, and provides scheduling, input-output control, file and data management, memory management, and communication control and related services.
[0130] Application 507 may be a source program, executable program (object code), script, or any other entity comprising a set of instructions to be performed. When a source program, then the program is usually translated via a compiler (such as the compiler 505), assembler, interpreter, or the like, which may or may not be included within the memory 502, so as to operate properly in connection with the operating system 504. Furthermore, the application 507 can be written as an object oriented programming language, which has classes of data and methods, or a procedure programming language, which has routines, subroutines, and/or functions, for example but not limited to, C, C++, C#, Pascal, BASIC, API calls, HTML, XHTML, XML, ASP scripts, JavaScript, FORTRAN, COBOL, Perl, Java, ADA, NET, and the like.
[0131] The I/O devices 503 may include input devices such as, for example but not limited to, a mouse, keyboard, scanner, microphone, camera, etc. Furthermore, the I/O devices 503 may also include output devices, for example but not limited to a printer, display, etc. Finally, the I/O devices 503 may further include devices that communicate both inputs and outputs, for instance but not limited to, a network interface controller (NIC) or modulator/demodulator (for accessing remote devices, other files, devices, systems, or a network), a radio frequency (RF) or other transceiver, a telephonic interface, a bridge, a router, etc. The I/O devices 503 also include components for communicating over various networks, such as the Internet or intranet.
[0132] When the computer 500 is in operation, the processor 501 is configured to execute software stored within the memory 502, to communicate data to and from the memory 502, and to generally control operations of the computer 500 pursuant to the software. The application 507 and the operating system 504 are read, in whole or in part, by the processor 501, perhaps buffered within the processor 501, and then executed.
[0133] When the application 507 is implemented in software it should be noted that the application 507 can be stored on virtually any computer readable medium for use by or in connection with any computer related system or method. In the context of this document, a computer readable medium may be an electronic, magnetic, optical, or other physical device or means that can contain or store a computer program for use by or in connection with a computer related system or method.
[0134] The present invention may, for instance, be applied in the field of patient monitoring. In particular, the method 200 and apparatus 100 provided herein may be applied as an early warning for sudden deterioration of patients being monitored in a ward, and for investigation of sleep disorders. For the latter, measurements tend only to be done in a spot-check fashion when a patient is visiting a doctor. The present invention may enable continuous or semi-continuous monitoring, which may assist such investigations.
[0135] Embodiments of the present invention provide a method of positioning a sweat sensor device, e.g. a sweat analyte concentration determining apparatus as disclosed in our non-prepublished application EP 3622880 A1, in such a way, that the first part of the sweat sensor device is attached on a first skin location (i), which first skin location (i) contains apocrine sweat glands and is found in the axillae or areola or ear canal or eyelids or wings of the nostril or inguinal or perineal, or perianal regions of a mammalian subject, while the second part of the sweat sensor device is attached on a second skin location (ii) which second skin location (ii), is adjacent to the first skin location (i), namely adjacent to the axillae or areola or ear canal or eyelids or wings of the nostril or inguinal or perineal, or perianal regions of a mammalian subject, having a different sweat gland composition than the first skin location, where predominantly eccrine sweat glands are present and apocrine glands may not be present.
[0136] determining 410 a first skin location (i) of a mammalian subject, which first skin location (i) contains apocrine sweat glands;
[0137] determining 420 a second skin location (ii), adjacent to the first skin location (i), and having a different sweat gland composition than the first skin location; and
[0138] positioning 430 the sweat sensor device 100 such that a first part 160 of the sweat sensor device 100 is present on the first skin location (i), while a second part 161 of the sweat sensor device 100 is present on the second skin location (ii).
[0139] The determining of the first (i) and second (ii) skin locations is achieved by detecting differences between the first (i) and second (ii) skin locations. As will be described in more detail below, such differences may be reflectivity, image of sweat on the skin, conductance, volatile organic compounds excretions, hydrophilic and hydrophobic properties, sliding resistance, skin pattern, sweat secretion behavior, and analytes uniquely excreted at the first skin location (i). Positioning of the sweat sensor device 100 to the first (i) and second (ii) skin locations may be done after determining the first skin location (i) and second skin location (ii) by means of a sweat sensor positioning device 300. Alternatively, the steps of determining the first (i) and second (ii) skin location and the step of positioning the sweat sensor device 100 may be done simultaneously, by positioning the sweat sensor device 100 on the skin and sliding it, until the first (i) and second (ii) skin locations are determined. Alternatively, the steps of determining the first (i) and second (ii) skin location and the step of positioning the sweat sensor device 100 may be done by positioning the sweat sensor device 100 on the skin and its correct positioning 430 is determined by employing parameters unique to eccrine or apocrine glands. Such parameters are uniquely excreted analytes by apocrine glands and unique sweat secretion behavior of eccrine and apocrine glands. The sweat sensor positioning device 300 and/or the sweat sensor device 100 may include a suitably programmed processor for carrying out the various method steps described below.
[0140]
[0141] A user may move the sweat sensor positioning device 300 over the skin or alternatively may position the sweat sensor positioning device 300 in discrete locations on the skin and take spot measurements. Alternatively, the positioning device may move autonomously, without the need of a user moving it over the skin.
[0142] The first skin locations (i) have a first skin reflectivity, as they have a first amount of sebum on the skin, and the second skin locations (ii) have a second skin reflectivity, higher than the first skin reflectivity, as they have a second amount of sebum on the skin, less than the first amount of sebum at first skin locations (i). The ratio of the first to the second amount of sebum is lower than 1. When the sweat sensor positioning device 300 passes the interface between first i and second ii skin locations, it records a change in reflectivity. If this change of reflectivity corresponds to the first amount of sebum which is greater than the second amount of sebum, then the sweat sensor positioning device 300 determines the first skin location (i) as the location with the first skin reflection, and the second skin location (ii) as the location with the second skin reflection.
[0143] After determining the first (i) and second (ii) skin locations, the sweat sensor positioning device 300 may notify the user by providing visual (e.g. light is turned on), acoustic (e.g. a sound is played) or haptic (e.g. vibrating) feedback.
[0144] The user may then remember the first (i) and second (ii) skin locations and attach the sweat sensor device 100 to the appropriate position on the skin. Alternatively they may use a means (e.g. a marker) to mark the first (i) and second (ii) skin locations and then attach the sweat sensor device 100 to the appropriate position on the skin. Alternatively, the sweat sensor positioning device 300 may integrate a means for marking the skin on the position of the first (i) and second (ii) skin locations (e.g. by means of ink).
[0145]
[0146] After determining the first (i) and second (ii) skin locations, the sweat sensor positioning device 300 may notify the user by providing visual (e.g. a light is turned on), acoustic (e.g. a sound is played) or haptic (e.g. vibrating) feedback.
[0147] The user may use the sweat sensor positioning device 300 to determine the first (i) and second (ii) skin locations. Alternatively, the image records of the camera may be analyzed by image recognition algorithms and the positioning device may automatically determine the first (i) and second (ii) skin locations.
[0148] The user may then remember the first (i) and second (ii) skin locations and attach the sweat sensor device 100 to the appropriate position on the skin. Alternatively the user may use a means (e.g. a marker) to mark the first (i) and second (ii) skin locations and then attach the sweat sensor device 100 to the appropriate position on the skin. Alternatively the sweat sensor positioning device 300 may integrate a means for marking the skin on the position of the first (i) and second (ii) skin locations (e.g. by means of ink).
[0149]
[0150] Alternatively, 2 or more GSR sensors, using 2 or more pairs of electrodes, may be used, in order to improve the conductance measurement.
[0151] The measured conductance will be different between the first (i) and second (ii) skin locations, because of the different density in eccrine glands. This difference in the measured conductance should be essentially zero when the electrodes are within the first (i) and second (ii) skin locations and should only show a difference when the electrodes are positioned one in the first (i) and the other in the second (ii) skin location. A user may slide a sweat sensor positioning device 300 using a GSR sensor over the skin. Alternatively, the sweat sensor positioning device 300 may move autonomously, without the need of a user sliding it over the skin. When the GSR sensor passes the interface between the first (i) and second (ii) skin locations, it records a change in conductance, identifying the location of said skin areas.
[0152] In
[0153]
[0154] After determining the first (i) and second (ii) skin locations, the sweat sensor positioning device 300 may notify the user by providing visual (e.g. light is turned on), acoustic (e.g. a sound is played) or haptic (e.g. vibrating) feedback.
[0155] The user may then remember the first (i) and second (ii) skin locations and attach the sweat sensor device 100 to the appropriate position on the skin. Alternatively, the user may use a means (e.g. a marker) to mark the first (i) and second (ii) skin locations and then attach the sweat sensor device 100 to the appropriate position on the skin. Alternatively, the sweat sensor positioning device 300 may integrate a means for marking the skin on the position of the first (i) and second (ii) skin locations (e.g. by means of ink).
[0156]
[0157] A first concentration of volatile organic compounds is observed at first (i) skin locations and a second concentration of volatile organic compounds at second (ii) skin locations. The first concentration of volatile organic compounds is expected to be higher than the second concentration at the second (ii) skin location, because the population of bacteria and concentration of sebum at the first (i) skin location are higher than at the second (ii) skin location, and bacteria consume sebum, producing volatile organic compounds.
[0158] When the sweat sensor positioning device 300 is positioned at a second (ii) skin location, the second concentration of volatile organic compounds will be detected and as the sweat positioning device 300 moves to a first (i) skin location, the first concentration of volatile organic compounds will be detected, being higher than the second concentration of volatile organic compounds. Therefore the sweat positioning device 300 detects the first (i) and the second (ii) skin locations.
[0159] Vice versa, when the sweat sensor positioning device 300 is positioned in a first (i) skin location, the first concentration of volatile organic compounds will be detected and as the sweat positioning device 300 moves to a second (ii) skin location, the second concentration of volatile organic compounds will be detected, being lower than the second concentration of volatile organic compounds. Therefore the sweat positioning device 300 detects the second (i) and the first (ii) skin locations.
[0160] Alternatively, the sweat sensor positioning device 300 may use two or more volatile organic compound sensors 305. The first (i) skin location is determined where a first group of sensors detects a first concentration of volatile organic compounds and the second skin location (ii) is determined where a second group or volatile organic sensors detects a second concentration of volatile organic compounds.
[0161] The sweat sensor positioning device 300 may also move autonomously, without the need of a user sliding it over the skin.
[0162] After determining the first (i) and second (ii) skin locations, the sweat sensor positioning device 300 may notify the user by providing visual (e.g. light is turned on), acoustic (e.g. a sound is played) or haptic (e.g. vibrating) feedback.
[0163] The user may then remember the first (i) and second (ii) skin locations and attach the sweat sensor device 100 to the appropriate position on the skin. Alternatively they may use a means (e.g. a marker) to mark the first (i) and second (ii) skin locations and then attach the sweat sensor device 100 to the appropriate position on the skin. Alternatively, the sweat sensor positioning device 300 may integrate a means for marking the skin on the position of the first (i) and second (ii) skin locations (e.g. by means of ink).
[0164]
[0165] The first part 160 is selected to be covered with an adherent material with hydrophilic properties 306, because as mentioned by Elkhyat et al in the book “Agache's Measuring the Skin” (Elkhyat A., Fanian F., Abdou A., Amarouch H., Humbert P. (2017) Influence of the Sebum and the Hydrolipidic Layer in Skin Wettability and Friction. In: Humbert P., Fanian F., Maibach H., Agache P. (eds) Agache's Measuring the Skin. Springer, Cham, 29 Apr. 2017, DOI https://doi.org/10.1007/978-3-319-32383-1_19, Print ISBN 978-3-319-32381-7, Online ISBN 978-3-319-32383-1) “The skin has a hydrophilic tendency on the sebaceous sites and a hydrophobic tendency on sites free of sebum. The degree of spreading of the water is a good indicator of the affinity of the skin with water. The role of the hydrolipidic film of the wettability of the skin is clearly demonstrated. The frictional behavior of the skin while contacting (touching) different materials plays a critical role in the skin's sensory perception of objects that we come into contact with”. Although sebaceous glands are distributed over the body surface, the number of sebaceous glands is different for various body locations. As said, the density of sebaceous glands is expected to be higher on the skin surface in the first (i) skin locations than on the second (ii) skin locations. Consequently, the hydrophilic/hydrophobic balance will be different for said skin surfaces.
[0166] In the field of adhesives, constantly new adhesive-compounds are developed with different properties. For instance, Adhesives Research's ARflow® proprietary hydrophilic adhesives are available as pressure-sensitive adhesives (PSAs), heat-seals and coatings.
[0167] The first 160 and second 161 parts of the sweat sensor device 100 and their adherent materials are covered with protective films. The protective film 310 of the second part 161 of the sweat sensor device 100 covers the whole area of the second part. In contrast, the protective film 309 of the first part 160 does not cover the whole area of the first part 160, and leaves a small opening, where the hydrophilic adhesive is uncovered, having a distance of preferably no more than 1 cm from the second part 161.
[0168] As the user slides the sweat device sensor device 100 over a skin, the opening leaving the hydrophilic adhesive uncovered will adhere to the first (i) skin location and therefore the first (i) skin location is determined. The second skin location (ii), is also determined and it is the skin area adjacent to the first (i) skin location. Afterwards the user may fixate the sweat sensor device 100 with a finger and peel off the 2 protective films 309, 310.
[0169] The sweat sensor device 100 may be made of flexible material and may be bent to aid the peel-off action. Sweat collection holes of the sweat sensor device should be positioned sufficiently far from the interface between the adhesives.
[0170]
[0171] The second part 161 is covered with the adherent material 312 with hydrophobic properties, because as mentioned by Elkhyat et al in the book “Agache's Measuring the Skin” (Elkhyat A., Fanian F., Abdou A., Amarouch H., Humbert P. (2017) Influence of the Sebum and the Hydrolipidic Layer in Skin Wettability and Friction. In: Humbert P., Fanian F., Maibach H., Agache P. (eds) Agache's Measuring the Skin. Springer, Cham, 29 Apr. 2017, DOI https://doi.org/10.1007/978-3-319-32383-1_19, Print ISBN 978-3-319-32381-7, Online ISBN 978-3-319-32383-1) “The skin has a hydrophilic tendency on the sebaceous sites and a hydrophobic tendency on sites free of sebum”.
[0172] The first 160 and second 161 parts of the sweat sensor device 100 and their adherent materials 311, 312 are covered with protective films 313, 314, respectively. The protective film 313 of the first part 160 of the sweat sensor device 100 covers the whole area of the first part 161. In contrast, the protective film 314 of the second part 161 does not cover the whole area of the second part 161, and leaves a small opening, where the hydrophobic adhesive is uncovered, with a distance of maximum 1 cm from the first part 160.
[0173] As the user slides the sweat device sensor 100 on a skin, the opening leaving the hydrophobic adhesive uncovered will adhere to the second (ii) skin location and therefore the second (ii) skin location is determined. The first skin location (i), is also determined and it is the skin area adjacent to the second (ii) skin location. Afterwards the user may fixate the sweat sensor device 100 with a finger and peel off the 2 protective films 313, 314.
[0174] The sweat sensor 100 device may be made of flexible material and may be bent to aid the peel-off action. Sweat collection holes of the sweat sensor device should be positioned sufficient far from the interface between the adhesives.
[0175]
[0176] The sweat sensor device 100 may be positioned at the second (ii) skin location, namely not in the axillae or areola or ear canal or eyelids or wings of the nostril or inguinal or perineal, or perianal regions of the subject and a user may slide it towards the first (i) skin location, namely the axillae or areola or ear canal or eyelids or wings of the nostril or inguinal or perineal, or perianal regions of the subject. When the user detects a change in the sliding resistance, as the the sweat sensor device 100 is slid over the subject's skin, then the interface between the second (ii) and the first (i) skin location has been surpassed and therefore the first skin location (i) has been determined. The second skin location (ii) is the skin area before the first part 160 of the sweat sensor device 100 is subject to the first sliding resistance.
[0177]
[0178] The sweat sensor device 100 may be positioned in the first (i) skin location, namely in the axillae or areola or ear canal or eyelids or wings of the nostril or inguinal or perineal, or perianal regions of the subject and a user may slide it towards the second (i) skin location, namely away from the axillae or areola or ear canal or eyelids or wings of the nostril or inguinal or perineal, or perianal regions of the subject. When the user detects a change in the sliding resistance, as the the sweat sensor device 100 is slid over the subject's skin, then the interface between the first (i) and the second (ii) skin location has been surpassed and therefore the second skin location (ii) has been determined. The first skin location (i) is the skin area before the second part 161 of the sweat sensor device 100 is subject to the second sliding resistance.
[0179]
[0180] The sweat sensor device 100 may be positioned on a skin of a subject and the user slides the device over the skin. In case that the first sliding resistance is higher than the third sliding resistance, and the second sliding resistance is higher than the fourth sliding resistance, and the sweat sensor device 100 is initially positioned at a second skin location (ii), and slides towards a first skin location (i), then the user may experience overall a moderate sliding resistance because the first part 160 shows the third sliding resistance. As the sweat sensor device 100 slides and the first part 160 reaches a first skin location (i), then the user will experience overall a high sliding resistance, as the first part will show the first sliding resistance, which is higher than the third sliding resistance. If the user continues to slide the sweat sensor device 100, that far that the whole device is located at a first skin location (i), then the user will again experience overall a moderate sliding resistance because the second part 161 will show the fourth sliding resistance which is lower than the second sliding resistance. Therefore the first skin location (i) is determined where the user experiences the highest sliding resistance, which is the location on the skin where the first part 160 is subject to the first sliding resistance and the second part 161 is subject to the second sliding resistance.
[0181] Proportionally, in case that the first sliding resistance is lower than the third sliding resistance and the second sliding resistance is lower than the fourth sliding resistance and the sweat senor is initially positioned at a second skin location (ii), and slides towards a first skin location (i), then the user may experience overall a moderate sliding resistance. This is caused because the first part 160 shows the third sliding resistance, which is higher than the first sliding resistance and the second part 161 shows the second sliding resistance which is lower than the fourth sliding resistance. As the sweat sensor device 100 slides and the first part 160 reaches a first skin location (i), then the user will experience overall a low sliding resistance, as the first part 160 will show the first sliding resistance, which is lower than the third sliding resistance and the second part 161 will still show the second sliding resistance which is lower than the fourth sliding resistance. If the user continues to slide the sweat sensor device 100, that far that the whole device is located at a first skin location (i), then the user will again experience overall a moderate sliding resistance because the second part 161 will show the fourth sliding resistance which is higher than the second sliding resistance. Therefore the first skin location (i) is determined where the user experiences the lowest sliding resistance, which is the location on the skin where the first part 160 is subject to the first sliding resistance and the second part 161 is subject to the second sliding resistance.
[0182] a. Optimal angular orientation between the regular skin patch-like structure and the print of the foil.
[0183] b. Using incident light that hits the skin under a small angle that will enhance the observation of the height differences of the regular skin patch-like structures and this will enhance the contrast as well.
[0184] c. The regular structure of the print may be adapted to gender and age.
[0185] d. Apply a thin biocompatible coating to the skin to enhance reflectivity, without clogging the sweat glands.
[0186] In
[0187]
[0188]
[0189] Pattern 330 does not have to be a repetitive feature of a skin pattern as illustrated in
[0190] The user moves the sweat sensor device 100 or the sweat sensor positioning device 300 on a skin. The orientation of the repetitive pattern 330 attached to the transparent foil 331 should not be parallel to the orientation of the repetitive pattern 330 attached to the transparent foil 321, in order to for a Moiré pattern to appear. As the user slides the sweat sensor device 100 or the sweat sensor positioning device 300 on a first skin location (i), no Moiré pattern appears, because sebum hides the pattern of the print attached to the transparent foil 331. When the sweat sensor device 100 or the sweat sensor positioning device 300 reaches a second skin location (ii), a Moiré pattern is observed though the through hole 320 and the second skin location (ii) is determined. The first skin location (i) is the skin area before a Moiré pattern is observed though the through hole 320.
[0191]
[0192]
[0193]
[0194]
[0195] a. Sweat sensor device 100 is wrongly placed on a second skin location (ii) only.
[0196] b. Sweat sensor device 100 is wrongly placed on a first skin location (i) only.
[0197] c. Sweat sensor device 100 is correctly placed on a first skin location (i) and a second skin location (ii).
[0198] d. Sweat sensor device 100 is wrongly placed, where a first part 160 is positioned on a second skin location (ii), but this first part 160 of the sweat sensor device 100 was intended for a first skin location (i). Moreover, where a second part 161 of the sweat sensor device 100 is positioned on a first skin location (i), but this second part 161 was intended for a second skin location (ii).
[0199] Only when sensor 104 is detecting a concentration of an apocrine gland analyte and sensor 127 is detecting no concentration of an apocrine gland analyte, the position of the sweat sensor device 100 is correct, which is illustrated in
[0200]
[0201]
[0202] a. Sweat sensor device 100 is wrongly placed on a second skin location (ii) only
[0203] b. Sweat sensor device 100 is wrongly placed on a first skin location (i) only
[0204] c. Sweat sensor device 100 is correctly placed on a first skin location (i) and a second skin location (ii).
[0205] d. Sweat sensor device 100 is wrongly placed, where a first part 160 is positioned on a second skin location (ii), but this first part 160 of the sweat sensor device 100 was intended for a first skin location (i). Moreover, where a second part 161 of the sweat sensor device 100 is positioned on a first skin location (i), but this second part 161 was intended for a second skin location (ii).
[0206] Only when sensor 194 is detecting a periodic sweat rate and sensor 195 is detecting a continuous sweat rate secretion, the position of the sweat sensor device 100 is correct, which is illustrated in
[0207] Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. Measures recited in mutually different dependent claims can be used advantageously combined. Any reference signs in the claims should not be construed as limiting the scope.