Patent ID: 12207922

DETAILED DESCRIPTION OF THE EMBODIMENTS

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.

Provided is a method of determining a concentration (Ca) of a first analyte (a) in sweat excreted by a first sweat gland type at a first skin location (i) having the first sweat gland type and a second sweat gland type which does not excrete sweat containing the first analyte. The method comprises measuring a first concentration (Cai) of the first analyte at the first skin location and measuring at least one parameter of sweat excreted by the second sweat gland type at a second skin location (ii) having the second sweat gland type but not the first sweat gland type. The at least one parameter is used to determine a dilution factor (Dai) which quantifies dilution of the first analyte by sweat excreted by the second sweat gland type at the first skin location. This dilution factor (Dai) is then used to correct the first concentration (Cai) so as to determine the concentration (Ca).

Various skin locations have both sweat glands of the first sweat gland type, e.g. the apocrine gland, and the second sweat gland type, e.g. the eccrine gland. When attempting to determine the concentration of a first analyte (a) excreted by glands of the first sweat gland type only at such a (first) skin location (i), the determination is hampered by the unknown, and potentially variable, dilution of the first analyte by the sweat excreted by glands of the second sweat gland type.

The present invention is based on the realisation that the dilution effect resulting from the sweat excreted by glands of the second sweat gland type at the first skin location (i) may be quantified by measuring at least one parameter of sweat excreted by the second sweat gland type at a second skin location (ii) which has the second sweat gland type but not the first sweat gland type. This is because the respective average secretion rates of glands of the second sweat gland type at the first and second skin locations may either be equal, for instance when the first and the second skin locations are relatively clo se together, or may at least be proportional to each other in a predictable way. Alternatively or additionally, the respective concentrations of a second analyte solely excreted by the second type of sweat gland at both the first skin location and second skin location may be equal, or proportional to each other. However at the first skin location, the measured concentration of the second analyte is lowered due to dilution by sweat of the first sweat gland type. By measuring the concentration of the second analyte at both skin locations, the dilution at the first skin location may be determined and this also enables determination of the dilution of the first analyte at the first skin location.

This enables determination of a dilution factor (Dai) quantifying dilution of the first analyte by sweat excreted by the second sweat gland type at the first skin location (i) using the at least one parameter of sweat excreted by the second sweat gland type at the second skin location (ii). This dilution factor factor (Dai) is then used to correct a measured first concentration (Cai) of the first analyte for dilution by the sweat excreted by glands of the second sweat gland type at the first skin location (i).

The present invention thus provides a differential measuring method (and a related apparatus) for determining the corrected concentration (Ca). The first skin location (i) may, for instance, have apocrine and eccrine glands. By measuring the first concentration (Cai) 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) which has eccrine glands only, the undiluted concentration of the first analyte (a) in the apocrine sweat may be determined unambiguously.

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.

FIG.1shows an apparatus100according to an embodiment. The apparatus100comprises a single patch102which is positioned on, e.g. adhered to, a first skin location i, as represented by the darker pattern on the left hand side ofFIG.1, and a second skin location ii which is adjacent the first skin location i. A single patch102spanning the adjacent first i and second ii skin locations may mean that the respective average secretion rates of glands of the second sweat gland type at the first i and second ii skin locations may be equal, or close to equal, which may simplify calculation of the dilution factor (Dai). Alternatively, the apparatus100may include two separate patches, e.g. for respectively attaching to non-adjacent first i and second ii skin locations.

Whilst not apparent from the plan view provided inFIGS.1and2, the patch102may include a first layer which contacts the skin and a second layer disposed on the first layer, such that the first layer is effectively interposed between the skin and the second layer. The second layer may cover the various sweat sampling and sensing components of the patch102.

As shown inFIG.1, the apparatus100comprises a first sensor104. The first sensor104is for measuring a first concentration (Cai) of the first analyte at the first skin location i. Sweat is collected from the first skin location i by a first collection hole106in the first layer and transported to the first sensor104via a channel108. The channel108extends past the first sensor104and terminates at an air vent110delimited by the second layer.

The first sensor104may employ any suitable analyte concentration measurement principle, providing the first sensor104is 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.

A second sensor120,121is provided in the apparatus100for measuring the at least one parameter of sweat excreted by the second sweat gland type at the second skin location ii, which has the second sweat gland type but not the first sweat gland type.

In the embodiment shown inFIG.1, the second sensor includes a detector120for measuring a (third) concentration (Ceii) of the second analyte at the second skin location ii. The detector120is supplied with sweat by the channel124extending between the second collection hole122, which receives sweat from the second skin location ii, and the detector120. The channel124further extends beyond the detector120, and terminates at the air vent126.

The distance between the first and second sweat collection holes106,122(132inFIG.2) may be at least partly determined by intended sampling location(s). The distance separating the first and second sweat collection holes106,122(132inFIG.2) from each other may be, for example, at least about 1 cm, such as at least about 2 cm.

When, for example, the first sweat sensor104and the second sweat sensor120,121are included in a single patch, the first and second sweat collection holes106,122(132inFIG.2) may be separated from each other, i.e. the distance between the respective edges of the sweat collection holes106,122(132inFIG.2), by at least about 1 cm, such as at least about 2 cm.

Irrespective of whether the first and second sweat sensors104,120,121are included in a single patch, the first and second collection holes106,122(132inFIG.2) may each, for example, have a maximum area of about 2 cm2, such as an area of about 1 cm2.

The detector120may employ any suitable analyte concentration measurement principle, providing the detector120is able to measure the (third) concentration (Ceii) 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).

In the embodiment shown inFIG.1, a third sensor112is provided for measuring a (second) concentration (Cei) of a second analyte (e) at the first skin location i. The second analyte may be in sweat excreted by the second sweat gland type and may not be in sweat excreted by the first sweat gland type. The third sensor112is supplied with sweat by the channel116extending between the further first collection hole114, which receives sweat from the first skin location i, and the third sensor112. The channel116further extends beyond the third sensor112, and terminates at the air vent118.

The third sensor112may employ any suitable analyte concentration measurement principle, providing the third sensor112is able to measure the (second) concentration (Cei) 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).

An optional flow rate analyser128may be included in the apparatus100, as shown inFIG.1. This flow rate analyser128may, for instance, comprise a thin channel129extending around the patch102. The thin channel129, which is progressively filled with sweat via an additional collection hole130at the first skin location i, provides an indication of the flow rate from the first skin location i by measurement of the length of the thin channel129which becomes filled with sweat as a function of time. The term “thin” in this context (and in relation to the flow rate sensor121) refers to the channel129being thinner, i.e. having a relatively smaller diameter bore, in comparison to the channels108,116and124which are intended to carry sweat to the respective sensor/detector104,116and120, rather than providing an indication of flow rate.

Any suitable detection principle may be used to measure the degree of filling of the thin channel129. For example, the position of the meniscus in the thin channel129as a function of time may be determined from a suitable image. In this respect, the flow rate analyser128may include a camera (not shown), and the apparatus100may, for instance, include a controller (not shown inFIGS.1and2) loaded with suitable image analysing software for detecting the meniscus. Alternative flow rate sensing principles may also be contemplated, such as calorimetric flow sensing, temperature gradient driven flow sensing, etc.

Whilst the flow rate analyser128may be useful due to the dependency of concentrations of particular components on the sweat rate, this flow rate analyser128is not essential in the context of the embodiment shown inFIG.1for determining the dilution factor (Dai) which quantifies dilution of the first analyte by sweat excreted by the second sweat gland type at the first skin location i. The dilution factor (Dai) may be derived using the second concentration (Ceii) and the third concentration (Ceii), as respectively measured by the third sensor112and the detector120in the apparatus100as depicted inFIG.1, as will now be explained in more detail.

The first concentration (Cai) of the first analyte (a) at the first skin location i, as measured using the first sensor104, may be expressed in terms of the dilution factor (Dai) and the corrected concentration (Ca) in the following way:
Cai=Ca·Dai(Equation A).

Similarly, the second concentration (Cei) of the second analyte (e) at the first skin location i, as measured using the third sensor112, may be expressed in terms of a further dilution factor (Dei), 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 (Ce) in the following way:
Cei=Ce·Dei(Equation B).

The respective dilution factors Daiand Deiboth have values between 0 and 1, and are related to each other by the following equation:
Dai+Dei=1  (Equation C).

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:

Dai=1-CeiCeii.(Equation⁢⁢D)

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.
Ce=Ceii(Equation E);
This assumption holds particularly when the first and second locations i and ii are relatively close to each other, as may be the single patch102embodiments depicted inFIGS.1and2, providing that the patch102has an area, for example, in the order of only a few cm2. Note that in Equation E, Ceiiis the (third) concentration of the second analyte (e) at the second skin location ii. Substituting Equation E in Equation D gives Equation I:

Dai=1-CeiCeii.(Equation⁢⁢I)

Using Equation I, the second concentration (Cei) and the third concentration (Ceii) measured using the third sensor112and the detector120respectively, the dilution factor (Dai) may thus be determined. The corrected concentration (Ca) may then be calculated from the dilution factor (Dai) and the first concentration (Cai) using Equation II (obtained by rearranging Equation A):

Ca=CaiDai.(Equation⁢⁢II)

The units of the corrected concentration (Ca), the first concentration (Cai), the second concentration (Cei) and the third concentration (Ceii) may all be, for instance, mol/L. Whilst not essential, measuring a total sweat flow rate using the flow rate analyser128may permit assessment of the mean quantity of sweat that the subject is excreting, which may be used to refine the above calculations.

Whilst not shown inFIG.1, the apparatus100may optionally include a flow rate sensor for measuring a flow rate of sweat from the second sweat gland type at the second skin location ii. Such a flow rate sensor may be an alternative or in addition to the flow rate analyser128. Such a flow rate sensor may, as will be described in more detail in relation toFIG.2, provide an alternative means for estimating the dilution factor (Dai). This may, for example, provide verification or enable refinement of the dilution factor (Dai) derived from measuring the second Ceiand third Ceiiconcentrations of the second analyte (e).

Turning toFIG.2, an apparatus100according to an alternative embodiment is depicted. As in the case ofFIG.1, the apparatus100comprises a single patch102which is positioned on, e.g. adhered to, the first skin location i, as represented by the darker pattern on the left side of the apparatus100, and a second skin location ii which is adjacent the first skin location i. Alternatively, the apparatus100may include two separate patches, e.g. for respectively attaching to non-adjacent first i and second ii skin locations.

As shown inFIG.2, the apparatus100comprises a first sensor104for measuring a first concentration (Cai) of the first analyte at the first skin location i. Similarly to the embodiment shown inFIG.1, in operation of the apparatus100depicted inFIG.2sweat is collected from the first skin location i by a first collection hole106in the first layer of the patch102and transported to the sensor104via a channel108. The channel108extends past the first sensor104and terminates at an air vent110delimited by the second layer of the patch102.

The first sensor104may employ any suitable analyte concentration measurement principle providing the first sensor104is 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).

In the embodiment shown inFIG.2, the second sensor for measuring the at least one parameter of sweat excreted by the second sweat gland type at the second skin location ii comprises a flow rate sensor121. This flow rate sensor121may, for instance, comprise a thin channel131extending around the patch102. The thin channel131is interposed between the first and second layers of the patch102, and terminates at an air vent134which corresponds to an aperture delimited by the second layer. The thin channel131is progressively filled with sweat via a second collection hole132at the second skin location ii, and thus provides an indication of the flow rate from the second skin location ii by measurement of the length of the thin channel131which becomes filled with sweat as a function of time.

Any suitable detection principle may be used to measure the degree of filling of the thin channel131. For example, the position of the meniscus in the thin channel131as a function of time may be determined from a suitable image. In this respect, the flow rate sensor121may include a camera (not shown), and the apparatus100may include a controller (not shown inFIGS.1and2) loaded with suitable image analysing software. Alternative flow rate sensing principles may also be contemplated, such as calorimetric flow sensing, temperature gradient driven flow sensing, etc. Such flow rate sensing principles are well-known per se and will not be further described herein for the sake of brevity only.

The inclusion of the flow rate sensor121in the apparatus100shown inFIG.2means that the at least one parameter may include a flow rate of sweat from the second sweat gland type at the second skin location ii. The dilution factor Daimay be determined from this measured flow rate.

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 Daithe 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.

In an embodiment, determining the dilution factor (Dai) 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 (Dai).

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 (Dai) as function of the flow rate of sweat from the second sweat gland type (e.g. eccrine glands) at the second skin location ii.

The apparatus100shown inFIG.1may, for example, be used to determine the dilution factors (Dai) of each of the volunteers by measuring the second (Cei) and third (Ceii) concentrations of the second analyte (e) at the first i and second ii skin locations respectively, as previously described. A suitable flow rate sensor, such as the flow rate sensor121described above in relation to the apparatus100shown inFIG.2may be used to determine the flow rate of sweat from the second sweat gland type at the second skin location ii for each of the volunteers.

A correlation may thus be made between the dilution factor (Dai) 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 (Dai) for a flow rate measured using the flow rate sensor121of the apparatus100shown inFIG.2. In turn, the determined dilution factor (Dai) may then be used to determine the corrected concentration (Ca) from the first concentration (Cai). The predetermined correlation may thus effectively permit extrapolation to zero flow rate from the second sweat gland type (e.g. eccrine glands) at the first skin location i such that the corrected concentration (Ca) may be determined.

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 inFIG.2, only two sensors are required which may make the apparatus100simpler and cheaper to produce. On the other hand, additional concentration sensors, such as the third sensor112and the detector120, as described in relation to the embodiment shown inFIG.1, and/or further flow rate analysers may optionally be included in the apparatus100shown inFIG.2.

At this point it is noted that the connections to and from the various sensors and detectors in the apparatuses100depicted inFIGS.1and2are not shown for the sake of clarity. These connections may, for instance, include wires for providing power to the sensors and/or for communicating the sensor/detector signals to a controller (not shown inFIGS.1and2) which records/displays the signals via a suitably configured user interface (not shown inFIGS.1and2). Alternatively or additionally, the patch (or patches)102may include an on-board chip with an antenna which can receive power wirelessly, and/or transmit the sensor/detector signals wirelessly to the controller recording the signal and/or providing power to the sensors/detectors.

Additional sensors may also be included in the apparatuses100shown inFIGS.1and2, which additional sensors may be employed to measure other components originating from the first sweat gland type, i.e. in addition to the first analyte (a). The same techniques as explained above may be used to correct for the dilution due to sweat from glands of the second sweat gland type at the first skin location i.

FIG.3shows a flowchart of a method200according to an embodiment. In step210, a first concentration (Cai) of the first analyte at a first skin location (i) is measured. This may be achieved using the first sensor104of the apparatus100, as previously described.

In step220, 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 the second sweat gland type but not the first sweat gland type. The at least one parameter is then used in step260to determine a dilution factor (Dai) which quantifies dilution of the first analyte by sweat excreted by the second sweat gland type at the first skin location d). In step270, the first concentration (Cai) is corrected using the dilution factor (Dai) so as to provide a corrected concentration (Ca) of the first analyte (a).

Measuring220the 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 sensor121of the apparatus100shown inFIG.2. In such a scenario, the using260the at least one parameter to determine the dilution factor (Dai) may comprise using a predetermined correlation between the flow rate and the dilution factor (Dai), as previously described.

Alternatively or additionally, the method200may further comprise measuring230a second concentration (Cei) 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 sensor112of the apparatus100shown inFIG.1. In such an embodiment, measuring220the at least one parameter includes measuring a third concentration (Ceii) of the second analyte at the second skin location (ii), which may be achieved using the detector120of the apparatus100shown inFIG.1.

Using260the at least one parameter to determine the dilution factor (Dai) may comprise calculating the dilution factor (Dai) using the second concentration (Cei) and the third concentration (Ceii), e.g. using Equation I, as previously described. Determining270the corrected concentration (Ca) from the first concentration (Cai) using the dilution factor (Dai) may use Equation II.

The method200may further include steps which enable anatomical variations in sweat gland density and sweat gland activation levels to be accounted for. Whilst the apparatuses100shown inFIGS.1and2include a single patch102, this is not intended to be limiting. Alternatively, a first patch may be attached to the first skin location (i) and a second patch may be attached to the second skin location (ii). In such an embodiment, the first sensor104is included in the first patch and the second sensor120,121is included in the second patch.

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 patch102. 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.

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.

The method200may therefore include the following additional steps, which account for regional variations in both the sweat gland density and the sweat gland secretion/discharge rate.

In step240, a ratio (Ract) 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 step250, a value is generated using the at least one parameter and the ratio (Ract). In this case, the value is used in step260to determine the dilution factor (Dai).

In an embodiment, the ratio (Ract) is calculated using the following equation:

Ract=SRie·GDiieSRiie·GDie;(Equation⁢⁢III)

wherein SRieand SRieare local sweat rates for the glands of the second sweat gland type at the first (i) and second (ii) skin locations respectively, and GDieand GDiieare local densities of the glands of the second sweat gland type at the first (i) and second (ii) skin locations respectively.

Equation III may be derived in the following way. The local sweat rate of the second sweat gland type at a given location (SRloCe) may be expressed as:
SRloCe=SRage·Nage(Equation F);

wherein SRageis the average sweat rate per activated gland of the second sweat gland type and Nageis the average number of activated glands of the second sweat gland type.
Nage=rloce·GDloce·Apatch(Equation G);

wherein rloceis the local ratio of active to inactive glands of the second sweat gland type, GDloceis 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 Apatchis the patch area (which is a known quantity).

The sweat rate is measured at two different skin locations (i) and (ii), yielding two different sweat rates, SRieand SRiie, respectively:
SRie=SRag;ie·Nag;ie=SRag;ie·rie·GDie·Apatch;i(Equation H);
SRiie=SRag;iie·Nag;iie=SRag;iie·riie·GDiie·Apatch;ii(Equation J);

Rearranging Equations H and J gives:

SRag;ie·rie=SRieGDie·Apatch;i;(Equation⁢⁢K)SRag;iie·riie=SRiieGDiie·Apatch;ii.(Equation⁢⁢L)

Dividing Equation K by Equation L gives:

SRa,g;ie·rieSRag;iie·riie=SRieSRiie·GDiie·Apatch;iiGDie·Apatch;i;(Equation⁢⁢M)

Assuming for simplicity that Apatch;ii=Apatch;i(i.e. the patch areas at the two skin locations are the same) and grouping

SRa,g;ie·rieSRag;iie·riie
into a single term, Ract, which captures the ratio of the local activation level of the sweat glands at the two sites, Equation M simplifies to:

Ract=SRieSRiie·GDiieieGD.(Equation⁢⁢III)

If rieis assumed to equal riie(i.e. the ratio of active to inactive sweat glands at the two sites is the same) then the ratio Ractof sweat gland activity

(SRa,g;ieSRag;iie)
at the first and second skin locations may be estimated.

The ratio Ractmay be used, for instance, to correct the measured (third) concentration of the second analyte (Ceii) at the second skin location (ii), for situations where the assumption that Ce=Ceii(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 Ceiimay be corrected by multiplying by Ract. The resulting value may then be used in determining the dilution factor (Dai) using Equation I.

Alternatively, the ratio Ractmay be used to correct the measured (second) concentration of the second analyte (Cei) at the first skin location (i), in which case the (second) concentration Ceimay be corrected by multiplying by

1Ract.

To implement step240, 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.

In a non-limiting example, when the first and second patches are placed on the forehead and dorsal foot respectively, Ractat the peak sweat rate would be, using Equation III:

Ract=(2.5)*(119186)=1.6

The ratio119/186was derived from Table 3 provided in Taylor, and the number 2.5 for the ratio

SRieSRiie
has been derived from the graphs shown in FIG. 3 of Taylor. The latter ratio was determined at the peak local sweat rate at 16 minutes for the forehead and for the dorsal foot. Dividing the respective peak heights for the forehead and the dorsal foot gives 2.5.

Ract=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.

FIG.4shows a block diagram of an apparatus100according to an embodiment. The apparatus100includes the first sensor104and the second sensor120,121, and a controller150. The controller150receives information from the various sensors/detectors included in the apparatus100, as shown by the arrows pointing from the sensors/detectors to the controller150. This information may be communicated to the controller150via wires or wirelessly, as previously described.

In this embodiment, the controller150uses the at least one parameter measured by the second sensor120,121to determine the dilution factor (Dai). The controller150then determines the corrected concentration (Ca) from the first concentration (Cai) using the dilution factor (Dai). In other words, the controller150is configured to implement steps260and270of the method200described above.

When the second sensor comprises the flow rate sensor121, the controller150may determine the dilution factor (Dai) using the predetermined correlation between the flow rate and the dilution factor (Dai). The controller150may also be configured to detect the meniscus of the sweat in the thin channel131from a suitable image, i.e. during the process of determining the flow rate, as previously described.

Alternatively or additionally, when the apparatus100includes the third sensor112and the detector120, the controller150may determine the dilution factor (Dai) using the second concentration (Cei) and the third concentration (Ceii), e.g. using Equation I. The corrected concentration (Ca) may then be calculated from the dilution factor (Dai) and the first concentration (Cai) using Equation II, as previously described.

In an embodiment, the controller150is further configured to implement steps240and250of the method200. In this respect, the controller150may calculate the ratio (Ract) 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 controller150may then generate the value using the at least one parameter and the ratio (Ract), and determine the dilution factor (Dai) using the value.

As shown inFIG.4, the apparatus100includes a user interface155. As shown by the arrow pointing from the controller150to the user interface155, information received and/or computed by the controller150may be sent to the user interface155, which may then display the information. In particular, the user interface155may be used to display the corrected concentration (Ca) of the first analyte (a) determined by the controller150. The user interface155may include any suitable display type. For example, the user interface155may include a LED/LCD display, which may have touchscreen capability permitting entry of parameters by the user, e.g. sweat rate and/or sweat gland density values for use in the Ractcalculation, and so on.

FIG.5illustrates an example of a computer500for implementing the controller150described above.

The computer500includes, but is not limited to, PCs, workstations, laptops, PDAs, palm devices, servers, storages, and the like. Generally, in terms of hardware architecture, the computer500may include one or more processors501, memory502, and one or more I/O devices503that 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.

The processor501is a hardware device for executing software that can be stored in the memory502. The processor501can 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 computer500, and the processor501may be a semiconductor based microprocessor (in the form of a microchip) or a microprocessor.

The memory502can 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 memory502may incorporate electronic, magnetic, optical, and/or other types of storage media. Note that the memory502can have a distributed architecture, where various components are situated remote from one another, but can be accessed by the processor501.

The software in the memory502may include one or more separate programs, each of which comprises an ordered listing of executable instructions for implementing logical functions. The software in the memory502includes a suitable operating system (O/S)504, compiler505, source code506, and one or more applications507in accordance with exemplary embodiments.

The application507comprises numerous functional components such as computational units, logic, functional units, processes, operations, virtual entities, and/or modules.

The operating system504controls the execution of computer programs, and provides scheduling, input-output control, file and data management, memory management, and communication control and related services.

Application507may 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 compiler505), assembler, interpreter, or the like, which may or may not be included within the memory502, so as to operate properly in connection with the operating system504. Furthermore, the application507can 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.

The I/O devices503may include input devices such as, for example but not limited to, a mouse, keyboard, scanner, microphone, camera, etc. Furthermore, the I/O devices503may also include output devices, for example but not limited to a printer, display, etc. Finally, the I/O devices503may 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 devices503also include components for communicating over various networks, such as the Internet or intranet.

When the computer500is in operation, the processor501is configured to execute software stored within the memory502, to communicate data to and from the memory502, and to generally control operations of the computer500pursuant to the software. The application507and the operating system504are read, in whole or in part, by the processor501, perhaps buffered within the processor501, and then executed.

When the application507is implemented in software it should be noted that the application507can 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.

The present invention may, for instance, be applied in the field of patient monitoring. In particular, the method200and apparatus100provided 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.

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. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.