Patent Application
20250235149
This invention relates to an apparatus for transporting sweat droplets.
Non-invasive, semi-continuous and prolonged monitoring of biomarkers that indicate disease/health status and well-being is in demand for monitoring, for example, dehydration, stress, sleep, children's health and in perioperative monitoring.
Sweat, tear fluid and saliva may all be obtained non-invasively. Sweat is a particularly accessible biofluid, and is a rich source of information relating to the physiology and metabolism of a subject.
Some examples of clinical relevant components of sweat are Na+, Cl− and/or K+ to monitor dehydration, lactate as an early warning for inflammation (which is relevant to sepsis), glucose for diabetics and neonates, and cortisol in relation to sleep apnea and stress monitoring.
Continuous monitoring of high-risk patients, such as those with serious chronic conditions, pre- or post-operative patients, and the elderly, using sweat biomarker monitoring devices can provide higher quality diagnostic information than regular biomarker spot checks as normally done by repeatedly drawing multiple blood samples. Such continuous monitoring may be in a hospital setting or elsewhere. Human sweat alone or as mixture with sebum lipids may be an easily accessible source for biomarker measurements in wearable on-skin devices. For instance, cholesterol is an important biomarker associated with elevated risk in development of cardiovascular diseases. Inflammatory markers or cytokines, such as interleukins (e.g. TNF-α, IL-6) play an important role in the immune response and detection or disease monitoring of joint damage in rheumatoid and psoriatic arthritis, and bowel disease.
Persons in a sedentary state, such as hospital patients, have a minimal sweat rate and there is therefore a significant delay between sweat excretion and biomarker detection, which can prevent timely monitoring and early warning of any impending complication. The concentration of particular relevant biomarkers is sweat rate dependent and therefore sweat rate per gland has to be assessed for a clinically relevant interpretation. Conventional sweat sensing solutions have limited application since they require the monitored person to be engaged in exercise, and tend to use rather complex microfluidics and sensors to determine the sweat rate.
WO 2018/125695 A1 discloses wearable sweat biosensing devices with active sweat sampling. An active method is described for transporting sweat which utilizes the electromechanical effect of electrowetting. Electrowetting plates comprise a hydrophobic dielectric layer (e.g., Teflon) covering electrodes. A sweat coupling “wicking” component made of a hydrophilic material permits sweat from the skin surface to slowly diffuse over time to the electrowetting plates, whereupon the sweat is transported via the electromechanical effect. This approach is very time consuming, and may be ineffective for small sweat volumes due to evaporation. Moreover, the technique entails mixing of sweat received from the skin at different times, which is undesirable for reliable semi-continuous biomarker measurements.
WO 2021/074010 A1 discloses an apparatus for transporting sweat droplets to a sensor. The apparatus comprises a chamber for filling with sweat. The chamber has an inlet lying adjacent the surface of the skin, which inlet permits sweat to enter and fill the chamber. The chamber has an outlet from which a sweat droplet protrudes once the chamber has been filled. The apparatus further comprises a fluid transport assembly which is designed to enable the sweat droplet protruding from the outlet to become detached from the outlet of the chamber. The sweat droplet is subsequently transported by the fluid transport assembly to the sensor. Once the protruding droplet has been released from the outlet, the outlet is made available for a subsequent sweat droplet to protrude therefrom upon further filling of the chamber. The released sweat droplet is transported via the fluid transport assembly at least as fast as the subsequent sweat droplet protrudes from the outlet such that the respective sweat droplets do not contact each other before reaching the sensor. Thus, the apparatus supplies sweat to the sensor in a dropwise manner.
As noted above, it has been demonstrated in the literature that small droplets can be transported by electrowetting. Further, droplets can split and merge by utilizing electrowetting. Complex droplet manipulation of several droplets with electrowetting has been shown on a matrix of electrodes. When many electrodes are involved an active matrix driver layer has been used below the electrode matrix layer to reduce the final number of electrical connection to the control electronics of a device. This active matrix driver layer controls each electrode individually. However, when a wearable disposable patch format is in need, the costs for such a set-up may limit the application space.
The invention is defined by the independent claims. The dependent claims define advantageous embodiments.
According to an aspect there is provided an apparatus for transporting sweat droplets, the apparatus comprising: a plurality of chambers defined in a substrate, each of the chambers having an inlet for receiving sweat from the skin, and an outlet delimited by a surface of the substrate and arranged such that a sweat droplet forms and protrudes therefrom following filling of the chamber with sweat, wherein the outlets are radially grouped around a central portion of the surface of the substrate to define at least first, second and third groups of chambers; and an electrowetting arrangement comprising: a plurality of electrodes, each electrode being electrically chargeable and dischargeable, wherein the electrowetting arrangement comprises first, second, and third limbs of electrodes configured to permit transport of the sweat droplets from the first group, in the case of the first limb, to or towards a central region, similarly centrally from the second group, in the case of the second limb and similarly centrally from the third group, in the case of the third limb by charging and discharging of the electrodes; and a conductive trace arrangement arranged to electrically connect electrodes of the first, second, and third limbs to each other.
The radial grouping of the outlets around a central portion of the surface of the substrate may mean that the outlets of each of the groups, and in particular the first, second and third groups, are arranged in a radial segment defined between two (e.g. notional) radii extending from the central portion, and a portion of a (e.g. notional) boundary, for example circumference, circumscribing the plurality of chambers so that each of the plurality of chambers are located within the boundary.
The term “limb” may refer to an overall pathway of electrodes which carries the sweat droplets from the outlets of the respective group to or towards the central region. Each limb may include one or more series of electrodes, as described herein below.
The conductive trace arrangement can be regarded as providing electrical connections with and between the electrodes in a plane or level of the apparatus, with the electrodes being thereby connected in this plane or level by the conductive trace arrangement. The conductive trace arrangement is thus distinct from connections made between different planes, or between different levels, of the apparatus, such as Vertical Interconnection Access (VIA) connections. In other words, a VIA is an electrical connection between layers in a physical electronic circuit that goes through the plane of one or more adjacent layers.
By the first, second and third limbs transporting the sweat droplets centrally from the first, second and third groups respectively, the apparatus may be particularly suitable for incorporation in, for instance, a wearable sweat sensing device, e.g. in the form of a wearable patch.
In such a wearable sweat sensing device, one or more sensors are preferably arranged in the abovementioned central region of the apparatus to or towards which the sweat droplets are transported via (at least) the first, second and third limbs. The arrangement of the limbs, which in at least some embodiments can be regarded as a radial configuration of limbs, may assist to minimize the transportation distance from the outlet(s) positioned farthest from the central region to the sensor(s). This may, in turn, assist to minimize evaporation of sweat droplets during their transportation to the sensor(s).
Moreover, by the conductive trace arrangement being arranged to electrically connect electrodes of the first, second, and third limbs to each other, the physical design of the apparatus can be simplified and/or made more robust, e.g. since fewer vertical interconnect access (VIA) connections may be required and/or the use of matrix driver layer to control the charging and discharging of the electrodes may be obviated. Thus, the complexity of the manufacturing process, costs and sources of errors/breakdowns are reduced.
In some embodiments, the plurality of electrodes comprises a plurality of sets of electrodes, wherein each set comprises electrodes from the first, second and third limbs which are connected to each other.
In such embodiments, a first conductive trace included in the conductive trace arrangement may be configured to connect one of the electrodes of the first limb to one of the electrodes of the second limb, and a second conductive trace included in the conductive trace arrangement may be configured to connect said one of the electrodes of the second limb (connected to the electrode of the second limb) to one of the electrodes of the third limb.
The first limb may comprise at least one series of first electrodes, with each first electrode of the at least one series being configured to release and/or transport one of the sweat droplets protruding from a respective outlet in the first group. The sweat droplet pathway defined by the series of first electrodes may be regarded as a “level zero track”.
The first limb may comprise at least one further series of first electrodes configured to receive sweat droplets from each series of the at least one series of first electrodes, and transport the sweat droplets away, for example centrally away, from the at least one series of first electrodes. The sweat droplet pathway defined by the further series of first electrodes may be regarded as a “level one track”.
There may be no chambers, and hence no outlets, associated with the electrodes of the further series. Thus, the electrodes of the further series may be solely employed for transporting sweat droplets, e.g. to or towards at least one sensor.
In some embodiments, the first limb comprises an additional series of first electrodes, and the first limb comprises a plurality of said further series of first electrodes. In such embodiments, the additional series of first electrodes may be configured to receive sweat droplets from each of the plurality of further series of first electrodes, and transport said sweat droplets away, for example centrally away, from the plurality of further series of first electrodes. The additional series of first electrodes can be regarded as a level two track.
There may be no chambers, and hence no outlets, associated with the electrodes of the additional series. Thus, the electrodes of the additional series may be solely employed for transporting sweat droplets, e.g. to or towards at least one sensor.
Alternatively or additionally, the second limb comprises at least one series of second electrodes, with each second electrode of the at least one series being configured to release and/or transport one of said sweat droplets protruding from a respective outlet in the second group. The sweat droplet pathway defined by the series of second electrodes may be regarded as a level zero track.
The second limb may comprise at least one further series of second electrodes configured to receive sweat droplets from each series of the at least one series of second electrodes, and transport said sweat droplets away, for example centrally away, from the at least one series of second electrodes. The sweat droplet pathway defined by the further series of second electrodes may be regarded as a level one track.
In some embodiments, the second limb comprises an additional series of second electrodes, and the second limb comprises a plurality of said further series of second electrodes. In such embodiments, the additional series of second electrodes may be configured to receive sweat droplets from each of the plurality of further series of second electrodes, and transport said sweat droplets away, for example centrally away, from the plurality of further series of second electrodes. The additional series of second electrodes can be regarded as a level two track.
Alternatively or additionally, the third limb may comprise at least one series of third electrodes, with each third electrode of the at least one series being configured to release and/or transport one of said sweat droplets protruding from a respective outlet in the third group. The sweat droplet pathway defined by the series of third electrodes may be regarded as a level zero track.
The third limb may comprise at least one further series of third electrodes configured to receive sweat droplets from each series of the at least one series of third electrodes, and transport said sweat droplets away, for example centrally away, from the at least one series of third electrodes. The sweat droplet pathway defined by the further series of third electrodes may be regarded as a level one track.
In some embodiments, the third limb comprises an additional series of third electrodes, and the third limb comprises a plurality of said further series of third electrodes. In such embodiments, the additional series of third electrodes may be configured to receive sweat droplets from each of the plurality of further series of third electrodes, and transport said sweat droplets away, for example centrally away, from the plurality of further series of third electrodes. The additional series of third electrodes can be regarded as a level two track.
In some embodiments, the at least one series of first electrodes comprises a plurality of series of first electrodes, with each of the plurality of series of first electrodes intersecting with one further series of said at least one further series of first electrodes at different positions relative to each other along said one further series of first electrodes.
Thus, the level zero tracks may move sweat droplets onto several locations of the level one track. This may provide a spatially efficient arrangement which renders the apparatus particularly suitable for incorporation into, for instance, a wearable patch.
In some embodiments, the sweat droplets may be subsequently transported from such level one tracks (with which the level zero tracks intersect at different positions) onto a level two track, e.g. again exiting on several locations of the level two track, and finally the level two tracks may, for instance, transport droplets to or through each a sweat rate sensor and towards a central region at or proximal to which a biosensor may be located.
More generally, in some embodiments the at least one further series of first electrodes comprises a plurality of further series of first electrodes, with each of the plurality of further series of first electrodes intersecting with the additional series of first electrodes at different positions relative to each other along the additional series of first electrodes.
By optimizing the density of the chambers in this manner, a smaller wearable patch incorporating the apparatus can be placed on the skin, whilst maintaining sweat collection performance.
Alternatively or additionally, the at least one series of second electrodes may comprise a plurality of series of second electrodes, with each of the plurality of series of second electrodes intersecting with one further series of said at least one further series of second electrodes at different positions relative to each other along said one further series of second electrodes.
In some embodiments, the at least one further series of second electrodes comprises a plurality of further series of second electrodes, with each of the plurality of further series of second electrodes intersecting with the additional series of second electrodes at different positions relative to each other along the additional series of second electrodes.
Alternatively or additionally, the at least one series of third electrodes may comprise a plurality of series of third electrodes, each of the plurality of series of third electrodes intersecting with one further series of said at least one further series of third electrodes at different positions relative to each other along said one further series of third electrodes.
In some embodiments, the at least one further series of third electrodes comprises a plurality of further series of third electrodes, with each of the plurality of further series of third electrodes intersecting with the additional series of third electrodes at different positions relative to each other along the additional series of third electrodes.
In some embodiments, the apparatus may comprise four, five, six, seven, eight, nine, ten or more of the above-defined limbs.
In some embodiments, each limb is symmetrical due to having a mirror plane extending along a radial centerline of the limb.
In embodiments, in which each limb comprises the mirror plane, conductive traces of the conductive trace arrangement may change direction at said radial centerline of each limb. This may assist to reduce the number of VIAs.
Each direction change at the radial centerline of each limb may result in the conductive trace arrangement appearing star-shaped in plan.
More generally, the apparatus may comprise a further substrate on and/or in which the electrowetting arrangement and the conductive trace arrangement are arranged.
In some embodiments, the further substrate comprises a first radially extending edge and a second radially extending edge, with the limbs being arranged on and/or in the substrate between the first and second radially extending edges.
In certain embodiments, the conductive traces of the conductive trace arrangement extend from proximal to the first radially extending edge around to proximal to the second centrally extending edge.
VIAs may, for example, be provided proximal to the first and/or second radially extending edges. In certain embodiments, the apparatus may not include any VIAs, e.g. due to the process employed for fabricating the ends of the electrical traces proximal to the first and second radially extending edges.
The apparatus may comprise at least one of a first sweat rate sensor, a second sweat rate sensor, and a third sweat rate sensor. Such a first sweat rate sensor may be arranged downstream of the outlets of the first group and configured to determine a sweat rate from sweat droplets transported by the first limb. Similarly, the second sweat rate sensor may be arranged downstream of the outlets of the second group and configured to determine a sweat rate from sweat droplets transported by the second limb, and the third sweat rate sensor may be arranged downstream of the outlets of the third group and configured to determine a sweat rate from sweat droplets transported by the third limb.
More generally, the apparatus may include a sweat rate sensor per limb.
The apparatus may comprise a biosensor configured to determine a sweat analyte concentration. The biosensor may be arranged to receive sweat droplets transported thereto by the first, second and third limbs. The biosensor may thus be centrally positioned, e.g. in or proximal to the central region, such as at or proximal to the central region located on the abovementioned further substrate, in order to receive the sweat droplets transported thereto via the limbs.
In some embodiments, the apparatus comprises a sweat collector, such as an absorber/absorbent pad, arranged downstream of one of more sensors. In particular, such a sweat collector may be arranged downstream of the biosensor when such a biosensor is included in the apparatus.
Such a sweat collector may, for example, be arranged in a space, e.g. a radial segment space, defined between the above-described first and second radially extending edges.
The apparatus may comprise an electric field generator for charging and discharging each of the electrodes of the electrowetting arrangement such as to transport each said sweat droplet. The electric field generator may be connected to the electrodes via the conductive trace arrangement.
According to another aspect there is provided a wearable device, such as a wearable patch, comprising the apparatus described above.
In some embodiments, the wearable device comprises an attachment arrangement configured to enable attachment of the apparatus to a body part such that said inlets receive sweat from the skin of the body part.
Embodiments of the invention are described in more detail and by way of non-limiting examples with reference to the accompanying drawings, wherein:
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.
Sampling of sweat over time, for determining the sweat rate per gland and for determining biomarker concentration in sweat, is hampered by the small sweat rate especially in the case of persons in sedentary state: which can be as low as 0.1-0.3 nl per minute for one eccrine sweat gland. It has been shown that a ‘discretized sweat collection’, i.e. sweat collection of discrete sweat droplets, using electrowetting on dielectrics (EWOD) creates a unique way to optimize the sweat liquid flow towards a sweat rate sensor and a biosensor: the latter determining the concentration of a biomarker. In the literature often methods are described that collect sweat via a continuous flow of sweat, however, even to fill a small microfluidic chamber positioned on the human skin with a height of 50 μm can take tens of hours for a person in sedentary state. Hence, these methods are limited to persons with high sweat rate such as athletes and laborers doing heavy exercise. The presented ‘discretized sweat collection’ method can collect sweat in tens of seconds and typically uses another 10-30 seconds for transport to the sensors.
However, especially in sedentary state the active gland density is rather low: typically, 10 active glands per cm2. Note that this number does vary from individual to individual and varies per body location. To have sufficient sweat to serve the measurement of the biomarker concentration, the sampling of one cm2 of skin is desired. However, to allow sweat collection in the order of seconds the sweat collection chambers have to be very small in height and diameter. Due to the small diameter of typically 10 to 100 μm, and more typically between 20 to 60 μm, many of these chambers may be required, such as in the order of ten thousand. Each sweat droplet emerging from a hole of such a cylindrical chamber has to be transported to the sensors. With an EWOD trajectory these droplets can be transported in the order of a few tens of seconds to the sensors. However, each chamber has to be affiliated to an electrode, to enable transport by EWOD. Consequently, the EWOD trajectory requires a large number of electrodes, also in the order of ten thousand.
This increase of scale and complexity on the fluid side has an impact on the increase of complexity in terms of the electrical connections required for the EWOD trajectory. The need for droplet transport from the sweat collection chambers towards a centralized biosensor whilst dealing with a relatively large number of collection chambers where the sweat sample is discretized, i.e the sweat sample comprises discrete sweat droplets, creates a large number of electrical paths that need to cross each other. In order to achieve this, a large number of VIAs may be required and they add complexity, cost and generate a source of error/breakdown. Without optimization, the number of VIAs for a EWOD design, serving about 10,000 tiny collection chambers, may be large, e.g. in the order of several thousands. The alternative of employing a matrix driver layer may add to the cost and complexity and may be incompatible with the device being wearable.
Provided is an apparatus for transporting sweat droplets, e.g. to one or more sensors. The apparatus comprises a plurality of chambers for filling with sweat. Each chamber is defined in a substrate, and has an inlet lying adjacent the surface of the skin. The inlet permits sweat to enter and fill the chamber. Each chamber also has an outlet, delimited by a surface of the substrate, from which a sweat droplet protrudes once the chamber has been filled. The outlets are radially grouped around a central portion of the surface of the substrate to define at least first, second and third groups of chambers. The apparatus further comprises an electrowetting arrangement comprising a plurality of electrodes. Each of the electrodes is electrically chargeable and dischargeable. The electrowetting arrangement comprises at least first, second, and third limbs of electrodes configured to permit transport of the sweat droplets centrally from the first group in the case of the first limb, centrally from the second group in the case of the second limb, and centrally from the third group in the case of the third radial portion by charging and discharging of the electrodes. The electrowetting arrangement also includes a conductive trace arrangement arranged to electrically connect electrodes of the first, second, and third limbs to each other.
By the first, second and third limbs transporting the sweat droplets centrally from the first, second and third groups respectively, the apparatus may be particularly suitable for incorporation in, for instance, a wearable sweat sensing device, e.g. in the form of a wearable patch.
In such a wearable sweat sensing device, one or more sensors is or are preferably arranged in the central region of the apparatus to or towards which the sweat droplets are transported via the first, second and third limbs. The arrangement of the limbs, which in at least some embodiments can be regarded as a radial configuration of limbs, may assist to minimize the transportation distance from the outlet(s) positioned farthest from the central region to the sensor(s). This may, in turn, assist to minimize evaporation of sweat droplets during their transportation to the sensor(s).
Moreover, by the conductive trace arrangement being arranged to electrically connect electrodes of the first, second, and third limbs to each other, the physical design of the apparatus may be simplified and/or made more robust, e.g. since fewer vertical interconnect access (VIA) connections may be required to avoid short circuiting issues and/or the use of matrix driver layer to control the charging and discharging of the electrodes may be obviated.
Examples of VIA manufacturing processes include through-glass VIAs (TGVs) in glass substrates, redistribution layer (RDL) circuit patterning on glass, and channels and shaped VIA-forming in glass substrates. A VIA is an electrical connection between layers in a physical electronic circuit that goes through the plane of one or more adjacent layers. If well made, PCB VIAs may primarily fail due to differential expansion and contraction between the copper plating and the PCB in the out of plane direction (Z). This differential expansion and contraction may induce cyclic fatigue in the copper plating, eventually resulting in crack propagation and an electrical open. Various design, material, and environmental parameters will influence the rate of this degradation. This is especially relevant for wearable devices. Hence it is desirable to minimize the number of VIAs included in the electrowetting arrangement.
It is noted that the dropwise or discretized flow of sweat offers several unique benefits with respect to continuous flow. The delay between excretion of sweat and the actual determination of the biomarker concentration may be reduced, e.g. from typically 1-2 hours to about 10-15 minutes for subjects in a sedentary state. The capability of handling minute amounts of sweat and being able to transport this relatively rapidly to the sensor may enable, in the case of the sensor comprising a biomarker sensor, biomarker concentrations to be determined, even when subjects are in a sedentary state. Moreover, the sweat rate may be more straightforwardly determined, e.g. using simpler sensors, when the sweat is provided as discrete sweat droplets rather than as a continuous flow.
The inlet 104 is shown proximal to a sweat gland 108. In this case, the sweat excreted by the sweat gland 108 enters and fills the chamber 102 via the inlet 104. As shown in
The substrate 110 may be formed of any suitable material, e.g. a polymer, capable of being disposed on the skin. For example, the substrate 110 may have at least a degree of flexibility so as to enable conformal application to the surface of the skin 106. More rigid substrates 110 may also be contemplated, providing the inlet 104 can receive sweat from the skin 106.
In order to collect sweat from a subject, the substrate 110 may, for instance, be adhered to the surface of the skin 106 using a suitable adhesive. Alternatively, the substrate 110 may be held against the surface of the skin 106 by fastenings, e.g. straps, for attaching the substrate 110 to the body of the subject.
More generally, the apparatus 100 may be included in a wearable device, such as a wearable patch.
In some embodiments, the wearable device comprises an attachment arrangement, such as the above-described adhesive and/or fastenings, configured to enable attachment of the apparatus 100 to a body part such that said inlets 104 receive sweat from the skin 106 of the body part.
The respective areas of the inlet 104 and the outlet 114 may be selected to ensure efficient filling of the chamber 102 and sweat droplet formation over a range of sweat rates. In some examples, the inlet 104 and the outlet 114 have selected fixed dimensions for this purpose. In a preferred example, each chamber 102 is dimensioned to fill up with sweat at least within 10-15 minutes. The formation of the hemispherical sweat droplet following filling of the chamber 102 preferably occurs typically within 10 seconds at relatively low sweat rate, e.g. 0.2 nl/min/gland.
In an embodiment, each inlet 104 of the plurality of chambers 102 is dimensioned to receive sweat from, on average, 0.1 to 1 active sweat glands. This may assist the apparatus 100 to be used for determination of the sweat rate per sweat gland.
Each inlet 104 may, for example, have an area between 0.005 mm2 to 20 mm2. The inlet area may be selected according to the other dimensions of the chambers 102, and the number of chambers 102 included in the apparatus 100.
Once the chamber 102 has been filled with sweat, a sweat droplet protrudes from an outlet 114 of the chamber 102. In the example shown in
The volume of the chamber 102 may be minimized in various ways in order to minimize the time required to fill the chamber 102 with sweat. Such modifications may be, for instance, to the shape of each of the chambers 102, e.g. using a tapering shape which narrows in the direction of the outlet 114, inclusion of a porous material in the chambers 102, and so on.
The apparatus 100 comprises an electrowetting arrangement which is arranged to transport each sweat droplet protruding from a respective outlet 114. The electrowetting arrangement comprises a plurality of electrically chargeable and dischargeable electrodes 116.
In the non-limiting example shown in
The further substrate 118 may comprise a hydrophobic layer 118A for directly contacting the sweat droplets. Adjacent this hydrophobic layer 118A is at least one dielectric layer 118B, e.g. one, two or more dielectric layer(s) 118B. The electrodes 116 of the electrowetting arrangement are positioned adjacent the at least one dielectric layer 118B. Thus, the at least one dielectric layer 118B is interposed between the electrodes 116 and the hydrophobic layer 124A.
A sweat droplet that is partially in contact with such hydrophobic layer, will encounter a driving force and the counter forces, viscous drag and contact angle hysteresis when an electrode 116 is charged beneath the surface where the droplet is partially overlapping with. The driving force is created by a surface energy gradient which promotes the motion of the sweat droplet whereas viscous drag and contact angle hysteresis opposes the motion of the sweat droplet. The contact angle hysteresis acts as a resistant force to the movement, trying to retain the sweat droplet in its static position. The sweat droplet accelerates under the resultant force of these opposing forces.
Charging of an electrode 116, directly above the hydrophobic layer 118A, will lower the contact angle between the sweat droplet and this layer: causing a pulling force for the sweat droplet to move completely to this surface. Although the surface of hydrophobic layer does not necessarily change, one can speak of a layer switching from a hydrophobic to a hydrophilic property. The sweat droplet may correspondingly migrate onto a portion of the hydrophobic layer adjacent the charged electrode 116. Subsequent discharge of the charged electrode 116 and charging of the subsequent electrode 116 in the transport direction may cause the sweat droplet to migrate to a portion of the hydrophobic layer 118A adjacent the subsequent electrode 116, and so on. This sequence may be regarded as an “electrowetting wave”.
Thus, by coating the electrodes 116 with a hydrophobic layer 118A, such as a hydrophobic layer 118A comprising or consisting of a chloropolymer, for example a fluoropolymer, for example CYTOP® & Fluoropel, and charging/discharging of the electrodes 116 may permit switching of the hydrophobicity properties of the hydrophobic layer 118A. The layer 118B may be a parylene layer but can also be a layered coating of various substances, such as sputtering tantalum pentoxide or silicon-nitride on the electrode, coated with paralene and finally layer 118A is applied.
The use of an electrowetting arrangement in order to transport/migrate sweat droplets may offer relatively rapid migration and precise control over the transport, e.g. velocities, of the sweat droplets. The propagation of the electrowetting wave may, in principle, be applied to transport sweat droplets over relatively long distances.
An electric field generator (not visible) connected to the electrodes 116 may be used to charge/discharge the electrodes 116. The electric field generator may, for example, be included in the apparatus 100, and in particular the electrowetting arrangement. In other examples, the electric field generator is supplied separately from the apparatus 100.
Controlled local voltages may be employed to generate multiple electrowetting waves. Such electrowetting waves may affect transport/migration of the sweat droplet towards or to, and optionally through, one or more sensors (not visible in
In addition to the electrodes 116, the electrowetting arrangement may include a ground electrode 120. In the non-limiting example shown in
In at least some embodiments, the detachment or release of the sweat droplet from the outlet 114 may occur at the moment that the sweat droplet reaches a certain diameter.
In the non-limiting example shown in
Alternatively or additionally, sweat droplet detachment may be facilitated by the electrowetting arrangement. Detachment from the outlet 114 may occur when the sweat droplet has grown to acquire a sufficiently large diameter that the sweat droplet at least partially overlaps a pair of electrodes 116. In this case, once an electrowetting wave passes along the electrodes 116, the sweat droplet spanning the pair of electrodes 116 may be dislodged from the outlet 114 accordingly. In such an example, the sweat droplets may not be all of a uniform size or volume, because the sweat droplet may continue to grow to varying degrees in the period between the sweat droplet reaching the requisite diameter and the arrival of the electrowetting wave. In this respect, the sweat droplet size may be determined by the frequency of the electrowetting wave.
Accordingly, arranging the electrodes 116 in the further substrate 118 should not be regarded as being limiting, and in alternative non-limiting examples the electrodes 116 of the electrowetting arrangement may be arranged in the substrate 110. In the latter case, the sweat droplets may be released and transported along a hydrophobic layer 118A defining the upper surface of the substrate 110.
More generally, the released sweat droplet may be transported at least as fast as the subsequent sweat droplet protrudes from the outlet 114. Preferably, migration of a sweat droplet is faster than formation, i.e. the protruding, of the subsequent sweat droplet. This is in order to ensure unambiguous sweat droplet definition, i.e. to ensure transport of a train of discrete sweat droplet.
In other words, the fluid transport assembly may maintain the discrete droplet characteristics of the sweat droplets by ensuring rapid transport/migration relative to sweat droplet formation. This may have advantages over a continuous flow of sweat, especially at low sweat rates, in terms of lessening or avoiding diffusion of components, such as biomarkers, between sweat samples collected at different points in time.
It is also noted that, whilst not visible in the cross-sectional representation provided in
In the non-limiting example shown in
The sweat droplet pathway defined by the series 124 of electrodes 116 may be regarded as a “level zero track”, and the sweat droplet pathway defined by the further series 126 of electrodes 116 may be regarded as a “level one track”.
In the non-limiting example shown in
There may be no chambers 102, and hence no outlets 114, associated with, e.g. opposing, the electrodes 116 of the further series 126. Thus, the electrodes 116 of the further series 126 may, in such an example, be solely employed for transporting sweat droplets, e.g. to or towards at least one sensor (not visible in
By the electrodes 116 of the level zero tracks 124A-J being connected to each other in sets (numbered 1 to 5) in this way, the complexity of the electrical connection scheme connecting each electrode 116 to an electric field generator, e.g. an electronic control board of such an electric field generator, may be significantly reduced relative to the scenario in which each electrode 116 is connected to the electric field generator individually.
In the example shown in
It is noted that any suitable number of electrodes 116 can be used in each of the level zero track(s) 124A-J, for example two, three, four, five, six, seven, eight or more.
In some embodiments, the level one track 126 transports sweat droplets 128 towards and through a sweat rate sensor (not visible in
Moreover, in some embodiments a biosensor (not visible in
Since each sequence of electrodes (numbered 1 to 4) of the level one track 126 is followed by a subsequent sequence, each sweat droplet 128 can be seamlessly transported along the level one track 126 without interruption. Defining an electrowetting wave as sequential charging/de-charging of the sets of electrodes 116, in the example shown in
More generally, and referring to
Similarly, the second limb 136 comprises, or more specifically is defined by, a series of second electrodes 116B, each second electrode 116B of the series being configured to release and/or transport one of the sweat droplets protruding from a respective outlet in the second group of chambers 102. The second limb 136/series of second electrodes 116B in this example can thus be regarded as a level zero track.
With continued reference to
By the first, second and third limbs 134, 136, 138 transporting the sweat droplets 128 centrally, e.g. generally radially, from the first, second and third groups respectively, the apparatus 100 may be particularly suitable for incorporation in, for instance, a wearable sweat sensing device, e.g. in the form of a wearable patch.
In such a wearable sweat sensing device, one or more sensors, such as the above-described sweat rate sensor and/or biosensor, are preferably arranged in a central region of the apparatus 100 to or towards which the sweat droplets are transported via the first, second and third limbs 134, 136, 138. The arrangement of the limbs 134, 136, 138, which in at least some embodiments can be regarded as a radial configuration of limbs 134, 136, 138, may assist to minimize the transportation distance from the outlet(s) positioned farthest from the central region to the sensor(s). This may, in turn, assist to minimize evaporation of sweat droplets 128 during their transportation to the sensor(s).
The electrowetting arrangement also comprises a conductive trace arrangement arranged to electrically connect electrodes 116 of the first, second, and third limbs 134, 136, 138 to each other. By the conductive trace arrangement being arranged to electrically connect electrodes of the first, second, and third limbs 134, 136, 138 to each other, the physical design of the apparatus 100 may be simplified and/or made more robust, e.g. since fewer vertical interconnect access (VIA) connections may be required and/or the use of matrix driver layer to control the charging and discharging of the electrodes 116 may be obviated.
In some embodiments, such as the non-limiting example shown in
In such embodiments, a first conductive trace 140A; 140B; 140C; 140D; 140E of the conductive trace arrangement is configured to connect one of the electrodes 116A, particularly one of the series of first electrodes 116A in the case of the example shown in
The outlets 114 and affiliated electrodes 116A, 116B, 116C of the level zero tracks 134, 136, 138 shown in
In the non-limiting example shown in
In the non-limiting example shown in
In some embodiments, such as in the non-limiting example shown in
Each of the at least one series of first electrodes 116AA, 116AB, 116AC constitutes a level zero track, and each of the at least one further series of first electrodes 116AD constitutes a level one track.
The second limb 136 may also comprise at least one series of second electrodes 116BA, 116BB, 116BC, and at least one further series of second electrodes 116BD configured to receive sweat droplets from each series of the at least one series of second electrodes 116BA, 116BB, 116BC, and transport said sweat droplets away, in this case centrally away, from the at least one series of second electrodes 116BA, 116BB, 116BC.
Each of the at least one series of second electrodes 116BA, 116BB, 116BC constitutes a level zero track, and each of the at least one further series of second electrodes 116BD constitutes a level one track.
Similarly, the third limb 138 may comprise at least one series of third electrodes 116CA, 116CB, 116CC, and at least one further series of third electrodes 116CD configured to receive sweat droplets from each series of the at least one series of third electrodes 116CA, 116CB, 116CC, and transport said sweat droplets away, in this case centrally away, from the at least one series of third electrodes 116CA, 116CB, 116CC.
Each of the at least one series of third electrodes 116CA, 116CB, 116CC constitutes a level zero track, and each of the at least one further series of third electrodes 116CD constitutes a level one track.
Similarly to the example shown in
A first conductive trace 140A-O of the conductive trace arrangement is configured to connect one of the electrodes of the first limb 134 to one of the electrodes of the second limb 136. Moreover, a second conductive trace 142A-O of the conductive trace arrangement is configured to connect said one of the electrodes of the second limb 136 (connected to one of the electrodes of the first limb 134) to one of the electrodes of the third limb 138.
Moreover, in some embodiments, such as in the non-limiting example shown in
In the example shown in
In some embodiments, such as in the non-limiting example shown in
The additional series of first electrodes 116ADA can be regarded as a level two track.
In the non-limiting example shown in
Similarly to the examples shown in
The number of outlets 114 and VIAs 144, 148 in the exemplary apparatuses 100 shown in
Many more outlets 114 may be required in certain cases. For instance, if each outlet 114 is 30 μm in diameter and the exit of the gland duct 108 onto the skin 106 is about 40 μm, the skin surface area that is sampled by one outlet 114 has a diameter of about 113 μm (providing at least partial overlap with the exit of a gland 108). Typically, in sedentary state about 10 eccrine glands are active per cm2 skin. To provide sufficient reliability one would like to measure about 10 glands. So, a cm2 of skin may be sampled. This would require about 10000 outlets 114. Note that with higher sweat production the number of active sweat glands per surface area can increase (typically a factor 2 to 10) but still a large amount of collection chambers may be required and hence the number of required VIAs is still significant. When a cauliflower design is provided for serving 10000 outlets 114, without using the teachings of this invention, the number of VIAs may be in the order of thousands. An extrapolation has shown that 4296 VIAs may be required.
In this example, the plurality of electrodes comprises a plurality of sets of electrodes, with each set comprising electrodes from the first, second, third, fourth, fifth, sixth, and seventh limbs 134, 136, 138, 152, 154, 156, 158. A first conductive trace 140 is configured to connect one of the electrodes of the first limb 134 to one of the electrodes of the second limb 136, a second conductive trace 142 is configured to connect said one of the electrodes of the second limb 136 to one of the electrodes of the third limb 138, a third conductive trace 160 is configured to connect one of the electrodes of the third limb 138 to one of the electrodes of the fourth limb 152, a fourth conductive trace 162 is configured to connect one of the electrodes of the fourth limb 152 to one of the electrodes of the fifth limb 154, a fifth conductive trace 164 is configured to connect one of the electrodes of the fifth limb 154 to one of the electrodes of the sixth limb 156, and a sixth conductive trace 166 is configured to connect one of the electrodes of the sixth limb 156 to one of the electrodes of the seventh limb 158.
Moreover, similarly to conductive traces 150A, 150B, 150C shown in
In some embodiments, including the non-limiting example shown in
A single sweat rate sensor 168 may be used in the apparatus 100, but preferably, a sweat rate sensor 168 is provided per limb 134, 136, 138. This may assist the apparatus 100 to determine a sweat rate per sweat gland. In the non-limiting example shown in
In the example shown in
The sweat rate sensor 168 may be configured to count the sweat droplets transported thereto, and in at some cases also determine the volume of each of the sweat droplets.
Any suitable sensing principle can be employed for the sweat rate sensor 168. For example, a capacitance sensing principle may be particularly useful for counting the sweat droplets. Such a sensing principle may also enable estimation of the time during which the sweat droplet passes through the detector, i.e. between the plates of the capacitor, since the dielectric change between air and a sweat droplet (about 99% water) is relatively large (about a factor of 80). The time taken for the sweat droplet to pass through the sweat rate sensor may be indicative of the volume of the sweat droplet.
Alternatively or additionally, the apparatus 100 may comprise a biosensor 170 configured to determine a sweat analyte concentration. The biosensor 170 may be arranged to receive sweat droplets transported thereto by each of the limbs 134, 136, 138, 152, 154, 156, 158.
In at least some embodiments, the apparatus 100 further comprises a sweat collector 172 downstream of the biosensor 170. The sweat collector 172 may provide a storage reservoir for sweat which has been analyzed by the biosensor 170. For example, the sweat collector 172 can be in the form of an absorber/absorbent pad, in other words an absorbent material, configured to absorb the sweat transported thereto.
The apparatus 100 shown in
In the example shown in
Further details can be observed from the enlarged views provided in
In the depicted example, the sweat collector 172 is arranged between the first and second radially extending edges 176A, 176B.
As best shown in
The level zero, level one, and level two tracks and the conductive traces are clearly observable in the enlarged view provided in
At this point it is noted that in the embodiments depicted in
The embodiment of
In this way, the average density of the chambers 102 may be larger, e.g. than with the design shown in
In this particular example, there are four electrodes 116 and so five outlets 114 affiliated to one level zero track. Also, another number of electrodes can be chosen, such as 5 or 6 or 7 electrodes per level zero track. Further, there are twelve level zero tracks affiliated to one level one track, although the number of level zero tracks per level one track may be less towards the centre of the electrowetting arrangement due to space limitations. In this example, each of the 11th level one tracks has nine level zero tracks and the last being the 12th level one tracks has six level zero tracks. Subsequently these twelve level one tracks connect to one level two track, and due to mirroring in total twenty four level one tracks are connected to one level two track (constituting one of the feather-like limbs 134, 136, 138, 152, 154, 156, 158).
There are thirty electrical paths to connect the most peripheral level zero tracks. In addition, there are 220 electrical paths to also connect all level one tracks to the level two tracks and finally about 25 electrical paths connect the level two tracks up to the biosensor 170. Consequently, there are 275 electrical paths starting proximal to one of the radially extending edges 176A, 176B and ending at the other of the radially extending edges 176B, 176A. This constitutes 55 groupings of five electrodes. Proximal to one of the radially extending edges 176A, 176B there are 2 VIAs per grouping and proximal to the other radially extending edge 176B, 176A there is one VIA of this grouping. So proximal to the first radially extending edge 176A there are in total 110 VIAs and proximal to the other radially extending edge there are in total 55 VIAs. This gives a total of 155 VIAs. Further, it can be calculated that twelve level one tracks including the affiliated level zero tracks can serve 675 outlets 114, and that one level two track, with affiliated level one and level zero tracks, can serve 1350 outlets 114. Since there are seven level-two tracks, the whole electrowetting arrangement serves 9450 outlets 114. Just for a comparison, scaling linearly to 10000 outlets 114 there are only about 175 VIAs required.
For comparison, individually addressed electrodes 116 of an electrowetting arrangement serving 10000 outlets would require 10000 VIAs. Thus, the design shown in
Electrical pathways for the electrodes numbered “1” and “4” are located proximal to the other radially extending edge 176A (not visible in
The VIAs 144B connect to an additional conductive trace 182 provided on a surface opposing the surface on which the electrical traces connecting the electrodes are arranged. Similarly, the VIAs 144A connect to another additional conductive trace 184 provided on the surface opposing the surface on which the electrical traces connecting the electrodes are arranged.
What remains is to calculate the transport time of a sweat droplet originating from the outlets 114 the furthest away from the biosensor 170 for the example depicted in
A typical step time of the electrowetting wave may be 0.1 to 1 second. The electrowetting wave may be defined as charging a first electrode, keeping the charge for a certain time, de-charging this electrode and during de-charging start this cycle on the adjacent subsequent electrode and so on, as previously described.
Assuming a step time of 0.1 second, the longest total transport time is 27.5 seconds for the non-limiting example shown in
Whilst
In
The ends of the conductive trace for the electrodes numbered 1 terminate furthest away from where the ends of the conductive trace for the other electrodes, followed by the electrodes numbered 2, and so on.
The ends of the conductive trace arrangement may, in the case of the example depicted in
In the step shown in
In the step shown in
Thus, and as best shown in
The isolator layer 186 could be for instance a ceramic layer or a polymer i.e. Parylene C. In the case the edge thickness of the isolator is decreasing too gradually, a state-of-the-art photolithographic process can be utilized to remove a part of the isolator layer, rendering an edge of the isolator with a more stepwise fashion in thickness. In short, an additional protective layer is applied that is subsequently illuminated through a photolithographic mask. Subsequently certain areas of this protective layer are washed away creating a pattern. Subsequently, an etching step is applied which removes the isolator layer in the appropriate locations, there were the protection layer was removed. Subsequently the protective layer is removed.
The apparatus, systems and methods of the present disclosure may be applied for non-invasive, semi-continuous and prolonged monitoring of biomarkers that indicate health and well-being, for example for monitoring dehydration, stress, sleep, children's health and in perioperative monitoring. As well as being applicable for subject monitoring in general, the present apparatus, systems and methods may be specifically applied to provide an early warning for sudden deterioration of patients in the General Ward and Intensive Care Unit, or for investigation of sleep disorders. Currently, measurements may only be made in a spot-check fashion when a patient is visiting a doctor, although it is noted that the present disclosure may also be usefully applied in performing such spot-check measurements.
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 advantageously be combined. Any reference signs in the claims should not be construed as limiting the scope.
| Number | Date | Country | Kind |
|---|---|---|---|
| 21200652.2 | Oct 2021 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/075717 | 9/16/2022 | WO |
