EP4374963A1

EP4374963A1 - Electrowetting apparatus and method of operating the same

Info

Publication number: EP4374963A1
Application number: EP22209197.7A
Authority: EP
Inventors: Eduard Gerard Marie Pelssers; Emma MOONEN
Original assignee: Koninklijke Philips NV
Current assignee: Koninklijke Philips NV
Priority date: 2022-11-23
Filing date: 2022-11-23
Publication date: 2024-05-29

Abstract

Provided is an electrowetting apparatus (100) suitable for transporting sweat droplets (124). The electrowetting apparatus comprises a plurality of electrodes (102) arranged to define a transportation path (104) along which the sweat droplets are transportable. An electrowetting transport control circuit (106) charges and discharges the plurality of electrodes in sequence along the transportation path to enable the sweat droplets to be transported along the transportation path. A sensing circuit (134) provides, via connection of the sensing circuit with at least one electrode (126) of the plurality of electrodes, an electrical signal indicative of droplet presence on the transportation path. A switch (140) enables switching between the electrowetting transport control circuit being connected to and disconnected from the at least one electrode whose connection with the sensing circuit enables the sensing circuit to provide the electrical signal. The capability to disconnect such electrode(s) from the electrowetting transport control circuit assists to alleviate noise from the latter interfering with droplet presence detection. Following the sensing circuit providing the electrical signal, the at least one electrode can be reconnected to the electrowetting transport control circuit to enable sweat droplet transportation via the at least one electrode to resume. Further provided is a method of operating such an electrowetting apparatus, and related computer program.

Description

FIELD OF THE INVENTION

This invention relates to an electrowetting apparatus suitable for transporting sweat droplets. The invention further relates to a method of operating such an electrowetting apparatus, and a related computer program.

BACKGROUND OF THE INVENTION

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 clinically 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-a, 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.
Examples of biomarkers that can be detected in eccrine/apocrine sweat are: small molecules such as urea, creatinine, cholesterol, triglycerides, steroid hormones (cortisol), glucose, melatonin; peptides and proteins, including cytokines such as IL-1alpha, IL-1beta, IL-6, TNF alpha, IL-8 and TGF-beta IL-6, cysteine proteinases, DNAse I, lysozyme, Zn-α2-glycoprotein, cysteine-rich secretory protein-3 and Dermcidin; and large biomarkers such as the Hepatitis C virus.
Capture species, such as antibodies, aptamers, molecular imprint polymers, etc., may be used to detect certain biomarkers via capture species binding specifically to the target biomarker. In other cases, biomarkers, such as lactate and glucose, may be electrochemically detected, e.g. using an enzymatic amperometric sensor.
As summarized by Mena-Bravo and de Castro in "Sweat: A sample with limited present applications and promising future in metabolomics", J. Pharm. Biomed. Anal. 90, 139-147 (2014), it has been found that the results from sweat sensing can be highly variable, and a correlation between values determined from blood and sweat samples appears to be lacking for various biomarkers. In this respect, historical studies in this area have involved relatively crude sampling techniques, such as collecting large sweat volumes in bags or textiles. Deficiencies in such techniques may have been a contributing factor to this apparent lack of correlation. The review of Mena-Bravo and de Castro thus highlights further key frustrations with conventional sweat sensing techniques in terms of the difficulty of producing enough sweat for analysis, the issue of sample evaporation, the lack of appropriate sampling devices, the need for trained staff, and issues relating to the normalization of the sampled volume.
Efforts have been made to address these issues by bringing wearable sensors into nearly immediate contact with sweat as it emerges from the skin. An example is the wearable patch presented by Gao et al. in "Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis", Nature 529, 509-514 (2016). The patch includes a sensor array for measuring Na⁺, K⁺, glucose, lactate, and skin temperature. However, the focus of this study is on the development and the integration of the sensors themselves which, whilst evidently crucial, does not address issues relating to sweat sample collection. The latter is mostly done by placing a several cm² sized absorbent pad between the skin and the sensor. The assumption is that, providing ample sweat is produced (hence tests are carried out on individuals that are exercising), the pad will absorb the sweat for analysis, and newly generated sweat will refill the pad and "rinse away" the old sweat. It is, however, likely that the time-dependent response of the sensor does not directly reflect the actual level of biomarkers over time because of accumulation effects. The sample collection and presentation to the published sensors may not be well-controlled so that continuous reliable sensing over a long period of time is difficult. Such patches may also not be designed to handle the tiny amounts of sweat that are produced under normal conditions, i.e. in the order of subnanoliters to nanoliters per minute per sweat gland.
Adult humans produce heat in the order of 100 Joules per second (100 Watt) when at rest. For a person wearing clothes at a temperature of around 22°C this heat is removed by passive means such as losing heat by conduction and convection. In this case, the core temperature remains constant. However, when i) a person engages in physical labor or exercise and/or ii) the ambient temperature is increased, such conduction/convection processes are insufficient to maintain the core temperature. To maintain homeostasis, the body induces dilation of blood vessels in the skin to cool the blood, and starts to produce sweat which by evaporation cools the skin.
The amount of sweat produced by persons at ambient temperature with only light exercise or light labor is relatively small as discussed by Taylor in "Regional variations in transepidermal water loss, eccrine sweat gland density, sweat secretion rates and electrolyte composition in resting and exercising humans", Extrem Physiol Med 2013; 2:4, and Simmers in "Prolonged and localised sweat stimulation by iontophoretic delivery of the slowly-metabolised cholinergic agent carbachol", Journal of Dermatological Science 89 (2018) 40-51". In the so-called thermal neutral zone, which is in the range of about 25°C to 30°C, the core temperature remains very stable and inducing sweat production is not required for cooling down the body. This zone is defined for a naked man at rest. For a person in a resting state wearing clothes, the thermal neutral zone is lower: in the range of about 13°C to 22°C. Hence, when the temperature is in this zone and the person is in a resting state, the sweat production is very low.
According to Taylor, in resting and thermal neutral conditions the sympathetic discharge (secretion by the coil of the sweat gland) may not elicit measurable sweating since sweat reabsorption may match its formation rate. Simmers measured the sweat production rates of persons that were wearing clothes, being exposed to an air-conditioned environment, doing primarily non-manual labor and found sweat rates with a typical value of about 0.3 nl/min/gland (values measured between zero and 0.7 nl/min/gland). When persons are at rest but at an elevated temperature of 36°C, a sweat production rate was measured by Taylor to be, on average, 0.36 mg·cm²·min^-1. When assuming 2.03 million sweat glands per 1.8 m² (skin area of an average person) and sweat density of 1 g/ml, the average sweat production is about 3.2 nl/min/gland. Due to the elevated temperature above the thermal neutral zone the body requires cooling and indeed the sweat production rate is increased.
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 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. Transport of the released sweat droplet may be via electrowetting.
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.

SUMMARY OF THE INVENTION

The invention is defined by the independent claims. The dependent claims define advantageous embodiments.
According to examples in accordance with an aspect of the invention, there is provided an electrowetting apparatus for transporting a sweat droplet, the electrowetting apparatus comprising: a plurality of electrodes arranged to define a transportation path along which the sweat droplet is transportable; an electrowetting transport control circuit for charging and discharging the plurality of electrodes connected to the electrowetting transport control circuit in sequence along the transportation path to enable the sweat droplet to be transported along the transportation path; a sensing circuit for providing, via connection of the sensing circuit with at least one electrode of the plurality of electrodes, an electrical signal for indicating droplet presence on the transportation path; and a switch configured to enable switching between said at least one electrode being connected to and disconnected from the electrowetting transport control circuit.
It is desirable to detect the presence of a sweat droplet on the transportation path, for example for the purpose of counting such detected sweat droplets produced over time in order to estimate a sweat rate per sweat gland. Moreover, providing such droplet presence detection functionality using electrode(s) already provided for electrowetting transportation may provide various advantages, including a simpler physical design in which requirement for a dedicated droplet sensor in addition to the electrowetting electrodes is obviated.
Various challenges have nonetheless been encountered in using electrode(s) employed for electrowetting transportation to provide droplet presence detection functionality. In particular, severe background noise from the electrowetting transport control circuit may hamper detection of relatively weak electrical signals associated with the presence of a sweat droplet. Moreover, droplet presence detection may be hampered by movement of the sweat droplet by the electrowetting transport control circuit away from the at least one electrode (whose connection with the sensing circuit enables the sensing circuit to provide the electrical signal) before the sensing circuit has been able to provide an electrical signal that is reliably indicative of the presence, or otherwise, of a sweat droplet.
For these reasons, the electrowetting apparatus comprises a switch that enables switching between the at least one electrode (whose connection with the sensing circuit enables the sensing circuit to provide the electrical signal) being connected to and disconnected from the electrowetting transport control circuit. The capability to disconnect, e.g. isolate, the at least one electrode from the electrowetting transport control circuit may assist to reduce interference with the electrical signal by noise associated with the electrowetting transport control circuit, thereby enabling discernment of relatively small signal differences corresponding to the presence or absence of a sweat droplet adjacent the at least one electrode.
Moreover, the switch may also enable, in some embodiments, a sweat droplet to be immobilized adjacent to the at least one electrode (whose connection with the sensing circuit enables the sensing circuit to provide the electrical signal) so that the electrical signal can be more reliably indicative of the presence, or otherwise, of a sweat droplet.
In some embodiments, the switch is configured to enable switching between a first configuration in which said at least one electrode is connected to the electrowetting transport control circuit and is disconnected from the sensing circuit, and a second configuration in which said at least one electrode is connected to the sensing circuit and is disconnected from the electrowetting transport control circuit. This may provide particularly convenient switching operation, since the connection of the at least one electrode (whose connection with the sensing circuit enables the sensing circuit to provide the electrical signal) to and disconnection from the sensing circuit may be respectively accompanied by disconnection from and connection to the electrowetting transport control circuit.
In some embodiments, the electrical signal is indicative of a capacitance between the at least one electrode and at least one counter electrode spaced apart from the at least one electrode.
In such embodiments, the transportation path may, for example, be between the at least one electrode and the at least one counter electrode.
The capacitance of a capacitor formed by the electrode(s) and the counter electrode(s) may be in the range 1 to 100 pF, such as typically about 2.5 pF. The difference in this typical value is in the order of about 0.5 pF between air and sweat. This is a relatively small value and noise may obscure the difference between air and a sweat droplet being between these electrodes. However, this noise may be decreased by controlling the switch to isolate the electrode(s), whose connection with the sensing circuit enables the sensing circuit to provide the electrical signal, from the electrowetting transport control circuit.
It is noted that implicit in the transport of the sweat droplet along the transportation path of the electrowetting apparatus is a hydrophobic region, e.g. a hydrophobic coating, that covers each of the plurality of electrodes. The hydrophobic region is contactable by the sweat droplet.
In embodiments in which the electrical signal is indicative of a capacitance between the at least one electrode and the at least one counter electrode, the hydrophobic region further serves to enable capacitance measurement because the hydrophobic region assists to electrically isolate the at least one electrode from the at least one counter electrode.
One or more layers of dielectric material may be interposed between the plurality of electrodes and the hydrophobic region.
Such dielectric material layer(s) may be provided for the primary purpose of facilitating electrowetting transport of the sweat droplet, but may also be beneficial in respect of the above-mentioned capacitance measurement. This is due to the dielectric material(s) contributing to electrical isolation of the at least one electrode from the at least one counter electrode.
It is also noted that a further hydrophobic region may be arranged between the counter electrode(s) and the transportation path. The further hydrophobic region may itself provide a degree of electrical isolation, although any deficiency in terms of the electrical isolation provided by the further hydrophobic region may be compensated by the above-described covering of the plurality of electrodes.
In some embodiments, the electrowetting transport control circuit is configured to implement the charging and discharging of the plurality of electrodes by controlling an electric field between each of the plurality of electrodes and the at least one counter electrode. Thus, the counter electrode may be advantageously utilized for both electrowetting transportation and droplet presence detection.
In some embodiments, the electrowetting apparatus comprises a further switch configured to enable switching between the at least one counter electrode being connected to and disconnected from the electrowetting transport control circuit, e.g. a ground of the electrowetting transport control circuit. This may further assist to reduce interference with the electrical signal by noise associated with the electrowetting transport control circuit.
In some embodiments, the plurality of electrodes comprises three or more sets of electrodes, with each set having two or more electrodes, and wherein the electowetting transport control circuit comprises a switching system that includes a switching element for each of the sets of electrodes, with each switching element being switchable to enable charging and discharging of a respective set of electrodes. In such embodiments, only the electrodes of a given set may be connected to each other, without electrical connections being present between electrodes that respectively belong to different sets.
Such sets of electrodes, with the switching element, e.g. relay, for each set may assist to reduce a number of electrical connections between the plurality electrodes and the switching system relative to, for example, a scenario in which each electrode of the plurality of electrodes were to be individually controlled.
In some embodiments, eight electrodes to four hundred electrodes may be included in each set.
When, for example, there are two to ten sets of electrodes, the number of electrodes in the plurality of electrodes may be sixteen to four thousand. Five sets of electrodes may result in the number of electrodes in the plurality of electrodes being forty to two thousand.
In some embodiments, the at least one electrode comprises, and in some embodiments consists of, a single electrode of one of the sets of electrodes. This may assist to mitigate the risk of an electrical signal deriving from one of the electrodes of a given set to which a sweat droplet is adjacent being rendered unmeasurable by electrical signals deriving from the other electrodes of the set to which no sweat droplet is adjacent, noting the relatively small capacitance difference between the sweat droplet and air.
During providing of the electrical signal by the sensing circuit, each of the electrodes may be connected to ground, except the electrode(s) whose connection with the sensing circuit enables the sensing circuit to provide the electrical signal.
Moreover, it may well be the case that a sweat droplet is located adjacent more than one electrode of the set, such that the at least one electrode comprising only a single electrode of the set may assist to avoid signal confusion associated with several sweat droplets being respectively adjacent electrodes of the same set, once again noting that eight electrodes to four hundred electrodes may be included in each set.
In some embodiments, the sensing circuit comprises a transimpedance amplifier arranged to convert a current in the sensing circuit to a voltage output.
Measuring a change in voltage arising from the presence of the sweat droplet may necessitate a relatively large resistor to pick up such a voltage signal, and this may also create a relatively large impedance that may cause increased electrical noise pickup. The transimpedance amplifier may enable measurement of the electrical current with a relatively low impedance electrical circuit, thereby minimizing pickup of environmental electrical noise.
An additional advantage may be that the distance between the electrodes and the transimpedance amplifier can be relatively large, and therefore no electrical amplification may be required to be implemented on a sweat sampling device, e.g. a wearable sweat sampling device. Rather, the electrical amplification may be instead located in a separate acquisition device. This can make product development easier, for instance without having to incorporate electrical amplification in a wearable sweat sampling device, e.g. via an application-specific integrated circuit (ASIC) included in the wearable sweat sampling device, e.g. an on-sweat patch ASIC.
In some embodiments, the transimpedance amplifier comprises a capacitor in parallel with a feedback resistor of the transimpedance amplifier.
The feedback resistor in combination with the capacitor may form a first frequency filter, in other words a high-pass filter. Such a capacitor may, for example have a capacitance in the range of 100 to 1000 pF, such as about 300 pF. Alternatively or additionally, the resistance of the feedback resistor may be in the range of 300 to 600 kQ, such as about 470 kQ.
In some embodiments, the electrowetting apparatus comprises one or more processors configured to control the switch to switch between said at least one of the plurality of electrodes being connected to and disconnected from the electrowetting transport control circuit.
Alternatively or additionally, the processor(s) may be configured to obtain the electrical signal while said at least one electrode is disconnected from the electrowetting transport control circuit.
For example, the one or more processors comprises: a first processor configured to control the switch to switch between said at least one electrode being connected to and disconnected from the electrowetting transport control circuit, and optionally to control the further switch to switch between said at least one counter electrode being connected to and disconnected from the electrowetting transport control circuit; and a second processor configured to obtain the electrical signal while said at least one electrode is disconnected from the electrowetting transport control circuit.
In some embodiments, the one or more processors is or are configured to obtain the electrical signal from the sensing circuit as an electrical signal as a function of time, and transform the electrical signal as a function of time to an electrical signal as a function of frequency.
Such a transform, for example Fourier transform, may provide a filter for significant improvement in noise reduction. The Fourier transform may provide a relatively high-quality filter.
In embodiments in which the sensing circuit includes the transimpedance amplifier, the output of the transimpedance amplifier, in the form of a voltage output as a function of time, may be fed into an algorithm executing the Fourier transform. Such an algorithm may be run on the processor(s).
As an alternative to the Fourier transform, the electrowetting apparatus may include a lock-in amplifier.
Such a lock-in amplifier enables selection of a certain frequency that is to be observed, and enables measurement of both the amplitude and the phase shift (with respect to the original AC signal as produced by an alternating current power supply included in the sensing circuit). The measured amplitude corresponds to the resistance, and the phase shift corresponds to the capacitance.
It is noted that, as well as enabling counting of sweat droplets, the electrowetting apparatus may enable a measure of a volume of a sweat droplet to be extracted from the electrical signal.
By counting the sweat droplets the sweat rate may be determinable. Moreover, an electrical signal resulting from a sweat droplet that is partially overlapping with the at least one electrode and the counter electrode may be measured, followed by measurement of an electrical signal resulting from a sweat droplet that fully covers these electrodes, and subsequently measurement of an electrical signal resulting from again the sweat droplet that is partially overlapping with these electrodes during movement of the sweat droplet along the transportation path.
The capacitance value during the partial overlap may contain the information on the volume of the droplet.
Whilst the manner in which the sweat droplets are formed may be designed to obtain sweat droplets of a uniform volume, some variation in volume may nonetheless arise. Moreover, two sweat droplets may merge along the transportation path. Hence part of the present disclosure concerns measurement of the droplet volume.
In some embodiments, the droplet volume measurement comprises continuously calibrating the measured value for the sweat droplet by measuring the electrical signal when the at least one electrode and the counter electrode are fully covered by a sweat droplet. The latter should be a constant value, however it is known that measurement between two electrowetting electrodes is not fully an ideal capacitor since it also contains a, although high, electrical resistance value (in the order of megaohms) and it is known that there is a drift in this resistance value. Since the isolated electrodes fully covered by a droplet should give the same value, the measurement in the case of the electrodes being partially covered by a droplet may be calibrated.
Alternatively or additionally, an external capacitor may be provided over the at least one electrode and the counter electrode.
In such embodiments, the resultant high pass filter may enable measurement on a plateau (the region where the signal is independent of the applied frequency), thereby rendering the measurement independent of drift in the resistance value.
More generally, the one or more processors may be configured to extract a measure of a volume of a sweat droplet from the electrical signal.
In some embodiments, the electrowetting transport control circuit comprises a first alternating current power supply that outputs an alternating voltage and the sensing circuit comprises a second alternating current power supply that outputs an alternating voltage.
In some embodiments, a supply voltage frequency of the first alternating current power supply is different from that of the second alternating current power supply. Thus, the supply voltage frequency may be appropriately selected according to the electrowetting transportation functionality of the electrowetting transport control circuit and according to the droplet presence sensing functionality of the sensing circuit.
Preferably, the supply voltage frequency provided by the first alternating current power supply is lower than that provided by the second alternating current power supply.
In some embodiments, a supply voltage frequency of the first alternating current power supply is in the range of 500 to 1500 Hz, such as about 1000 Hz.
Alternatively or additionally, a supply voltage frequency of the second alternating current power supply may be in the range of 2000 to 8000 Hz, preferably in the range of 3000 Hz to 7000 Hz, such as about 5000 Hz.
In some embodiments, a peak-to-peak amplitude voltage provided by the first alternating current power supply is different from that of the second alternating current power supply. Thus, the peak-to-peak amplitude voltage may be appropriately selected according to the electrowetting transportation functionality of the electrowetting transport control circuit and according to the droplet presence sensing functionality of the sensing circuit. Preferably, the peak-to-peak amplitude voltage provided by the first alternating current power supply is higher than that provided by the second alternating current power supply.
In some embodiments, the first alternating current power supply's peak-to-peak amplitude voltage is in the range of 25 to 100 V, preferably in the range of 70 V to 90 V, such as about 80 V.
Alternatively or additionally, the second alternating current power supply's peak-to-peak amplitude voltage may be in the range of 1 to 20 V, preferably in the range of 5 to 15 V, such as about 10 V.
Such an amplitude voltage of the second alternating current power supply has been found to be low enough to minimize the risk of the sensing circuit causing migration of the sweat droplet whose presence is being detected, whilst high enough to facilitate sensing, e.g. capacitive sensing, of such a sweat droplet.
It is noted that the electrowetting apparatus may include a plurality of transportation paths, with each electrowetting path being defined by a respective plurality of electrodes, for example with a plurality of electrowetting transport control circuits being included in the electrowetting apparatus, and each electrowetting transport control circuit charging and discharging electrodes of one of the pluralities of electrodes connected thereto in sequence along the respective transportation path to enable the sweat droplet to be transported along the respective transportation path.
In such embodiments, the sensing circuit may provide, via connection of the sensing circuit with an electrode belonging to each of the pluralities of electrodes, an electrical signal for indicating droplet presence on each of the respective transportation paths.
Each plurality of electrodes, e.g. together with its associated electrowetting transport control circuit, may be regarded as an "electrowetting structure". Thus, a single sensing circuit can be used to sense droplet presence on more than one electrowetting structure.
One potential benefit to the electrowetting apparatus including more than one electrowetting structure, such as two, three, four, five, or more electrowetting structures, is that the electrowetting apparatus may be still able to operate in a scenario in which one of the electrowetting structures is rendered inoperable, e.g. as a result of a manufacturing defect, such as a dust particle introduced during manufacture causing a broken electrical line (noting that the surface area in which the electrodes and electrical lines are provided may be relatively large relative to electronic chips, and thus may be slightly more susceptible to dust particle-related manufacturing errors).
More generally, the electrowetting apparatus according to any of the embodiments disclosed herein may be included in a sweat sampling apparatus comprising one or more chambers each having an inlet that receives sweat from skin.
At least part of the sweat sampling apparatus, such as the chamber(s) and the electrodes of the electrowetting apparatus may be included in a wearable device, such as a wearable patch.
In some embodiments, the wearable device comprises an attachment arrangement, such as adhesive and/or fastenings, configured to enable attachment of the at least part of the sweat sampling apparatus to a body part such that said inlet(s) receive sweat from the skin of the body part.
According to another aspect, there is provided a method of operating an electrowetting apparatus having a plurality of electrodes arranged to define a transportation path along which a sweat droplet is transportable, an electrowetting transport control circuit for charging and discharging the plurality of electrodes connected to the electrowetting transport control circuit in sequence along the transportation path to enable transportation of the sweat droplet, a sensing circuit, and a switch, the method comprising: controlling the switch to disconnect at least one electrode of the plurality of electrodes from the electrowetting transport control circuit; and obtaining, while the at least one electrode is disconnected from the electrowetting transport control circuit, an electrical signal from said at least one electrode for indicating droplet presence on the transportation path.
The electrowetting apparatus according to any of the embodiments disclosed herein may be operated in the method.
In some embodiments, the method further comprises controlling the switch to, following said obtaining, connect the at least one electrode to the electrowetting transport control circuit. Thus, the migration of droplet(s) along the transportation path can resume.
Further provided is a computer program comprising computer program code which, when executed on one or more processors, causes the one or more processors to perform all of the steps of the method according to any of the embodiments described herein.
One or more non-transitory computer readable media may be provided, which non-transitory computer readable media have a computer program stored thereon, with the computer program comprises computer program code which is configured, when the computer program is run on the one or more processors, to cause the one or more processors to implement the method according to any of the embodiments described herein.
The processor(s) may be, for example, the processor(s) included in the electrowetting apparatus described herein.
More generally, embodiments described herein in relation to the electrowetting apparatus may be applicable to the method and computer program, and embodiments described herein in relation the method and computer program may be applicable to the electrowetting apparatus.
These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the invention, and to show more clearly how it may be carried into effect, reference will now be made, by way of example only, to the accompanying drawings, in which:

FIGs. 1A to ID show various configurations of an electrowetting apparatus according to an example;
FIG. 2 shows a sensing circuit of an electrowetting apparatus according to an example;
FIG. 3 provides a block diagram of an electrowetting apparatus according to an example;
FIG. 4 schematically depicts part of a sweat collecting apparatus according to an example;
FIG. 5 schematically depicts part of a sweat collecting apparatus according to another example;
FIG. 6 schematically depicts part of an electrowetting apparatus according to a further example; and
FIG. 7 provides a flowchart of a method according to an example.

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 an electrowetting apparatus suitable for transporting sweat droplets. The electrowetting apparatus comprises a plurality of electrodes arranged to define a transportation path along which the sweat droplets are transportable. An electrowetting transport control circuit charges and discharges the plurality of electrodes in sequence along the transportation path to enable the sweat droplets to be transported along the transportation path. A sensing circuit provides, via connection of the sensing circuit with at least one electrode of the plurality of electrodes, an electrical signal indicative of droplet presence on the transportation path. A switch enables switching between the electrowetting transport control circuit being connected to and disconnected from the at least one electrode whose connection with the sensing circuit enables the sensing circuit to provide the electrical signal. The capability to disconnect such electrode(s) from the electrowetting transport control circuit assists to alleviate noise from the latter interfering with droplet presence detection. Following the sensing circuit providing the electrical signal, the at least one electrode can be reconnected to the electrowetting transport control circuit to enable sweat droplet transportation via the at least one electrode to resume. Further provided is a method of operating such an electrowetting apparatus, and related computer program.
FIGs. 1A to 1D schematically depict an electrowetting apparatus 100 according to an example. The electrowetting apparatus 100 includes a plurality of electrodes 102 whose arrangement defines a transportation path 104 along which sweat droplets are transportable. The electrowetting apparatus 100 further comprises an electrowetting transport control circuit 106 that charges and discharges the plurality of electrodes 102 in sequence along the transportation path 104 to enable the sweat droplets to be transported along the transportation path 104.
In some embodiments, such as that shown in FIGs. 1A to 1D, the electrowetting transport control circuit 106 comprises a switching system 108A, 108B, 108C, 108D, 108E configured to enable switching of each of the plurality of electrodes 102 from being connected to a first terminal of a first power supply 110 to being disconnected from the first terminal of the first power supply 110.
In such embodiments, and with continued reference to FIGs. 1A to 1D, the switching system 108A, 108B, 108C, 108D, 108E may be configured to enable switching of each of the plurality of electrodes 102 to being connected to ground 112 (and a second terminal of the first power supply 110) when disconnected from the first terminal of the first power supply 110.
Any suitable type of switching element can be employed for the switching system 108A, 108B, 108C, 108D, 108E. In some embodiments, such as that shown in FIGs. 1A to 1D, the switching system 108A, 108B, 108C, 108D, 108E comprises a set of relays that are each switchable to enable switching of each of the plurality of electrodes 102 from being connected to the first terminal of the first power supply 110 to being disconnected from the first terminal of the first power supply 110.
In such embodiments, a resistor 114A, 114B, 114C, 114D, 114E may be provided, for example included in, each of the relays of the switching system 108A, 108B, 108C, 108D, 108E.
The resistors 114A, 114B, 114C, 114D, 114E may assist to provide a controlled path for the current of the relay's coil when the relay's switch is opened. The resistor's 114A, 114B, 114C, 114D, 114E conversion of the energy of the coil's magnetic field to heat may permit the relay to switch relatively quickly, which may be particularly beneficial in this electrowetting transport control circuit 106 application.
The resistance of the resistors 114A, 114B, 114C, 114D, 114E may be in the range of 300 to 600 kQ, such as about 470 kQ.
Other relay designs can also be contemplated, for instance including a diode to control the path for the current of the relay's coil as an alternative or in addition to the resistor 114A, 114B, 114C, 114D, 114E.
It is noted at this point that a key is provided in FIGs. 1A to ID that indicates, in relation to the wiring diagrammatically represented in these Figures, electrical lines not being connected 116, electrical lines being connected 118, and switch/switching element, e.g. relay, positions 120.
More generally, in such an electrowetting apparatus 100, and irrespective of the design of the electrowetting transport control circuit 106, each of the plurality of electrodes 102 is covered with a hydrophobic region 122 that is contactable by the sweat droplet.
Any suitable hydrophobic material can be contemplated for the hydrophobic region 122. In some embodiments, the hydrophobic region comprises a chloropolymer and/or a fluoropolymer, for example CYTOP^® or Fluoropel.
In some embodiments, one or more layers of dielectric material is or are interposed between the plurality of electrodes 102 and the hydrophobic region 122.
Various different ways of covering the electrodes 102 in order to enable electrowetting transportation can be contemplated. In embodiments in which one or more dielectric layers is or are provided on the electrodes 102, such dielectric layer(s) may, for instance, include a parylene layer and/or a suitable inorganic layer, such as a tantalum pentoxide or silicon nitride layer coated, e.g. sputtered, on the electrodes 102. In embodiments in which a tantalum pentoxide or silicon nitride layer is coated on the electrodes 102, the tantalum pentoxide or silicon nitride layer may be coated with parylene, and a chloropolymer and/or fluoropolymer hydrophobic layer applied onto the parylene layer.
In the configuration of the switching system 108A, 108B, 108C, 108D, 108E shown in FIG. 1A, none of the electrodes 102 is charged via connection to the first terminal of the first power supply 110. Moreover, all of the electrodes 102 are discharged owing to the switching system 108A, 108B, 108C, 108D, 108E connecting each of the electrodes 102 to ground 112 in this configuration. Thus, the sweat droplet 124 shown on the transportation path 104 is in a static position adjacent the electrode 102 numbered "3" towards the right hand side of the transportation path 104.
In the configuration of the switching system 108A, 108B, 108C, 108D, 108E shown in FIG. 1B, each of the electrodes 102 numbered "4" is selectively charged via connection to the first terminal of the first power supply 110. In this particular example, the switching element 108D, e.g. relay, is actuated to connect the electrodes 102 numbered "4" to the first terminal of the first power supply 110.
Charging of the electrode 102 numbered "4" that is proximal to the sweat droplet 124 may lower the contact angle between the sweat droplet 124 and the hydrophobic region 122, and correspondingly cause the sweat droplet 124 to migrate onto a portion of the hydrophobic region 122 adjacent/facing the charged electrode 102 numbered "4", as shown in FIG. 1B.
By way of explanation, a sweat droplet 124 that is partially in contact with the hydrophobic region 122 may encounter a driving force and counter forces, in the form of viscous drag and contact angle hysteresis, when an electrode 102 is charged proximal to the surface of the hydrophobic region 122 that is being partially contacted by the sweat droplet 124. The driving force may be created by a surface energy gradient arising from charging of the electrode 102 which promotes the motion of the sweat droplet 124, whereas viscous drag and contact angle hysteresis oppose the motion of the sweat droplet 124. The contact angle hysteresis acts as a resistant force to the movement that tries to retain the sweat droplet 124 in its static position. The sweat droplet 124 accelerates under the resultant force of these opposing forces. Thus, the sweat droplet 124 may move from being adjacent the electrode numbered "3" in FIG. 1A to being adjacent the electrode numbered "4" in FIG. 1B due to the charging of the latter by the electrowetting transport control circuit 106.
In general terms, by discharge of an initially charged electrode 102 to which the sweat droplet 124 is adjacent and charging of a successive electrode 102 in a transport direction along the transportation path 104, the sweat droplet 124 may be caused to migrate to a portion of the hydrophobic region 122 adjacent the successive electrode 102, and so on. This sequence may be regarded as an "electrowetting wave".
The electrowetting transport control circuit 106 may be configured, in combination with the plurality of electrodes 102, to provide such an electrowetting wave.
The use of an electrowetting apparatus 100 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 124. The propagation of the electrowetting wave may, in principle, be applied to transport sweat droplets over relatively long distances.
It is noted, with continued reference to FIGs. 1A to 1D, that in addition to the plurality of electrodes 102, the electrowetting apparatus 100 may include at least one counter electrode 126. The electrowetting transport control circuit 106 may accordingly be configured to implement the charging and discharging of the plurality of electrodes 102 by controlling the electric field between each of the plurality of electrodes 102 and the at least one counter electrode 126.
In such embodiments, the transportation path 104 may be arranged between the plurality of electrodes 102 and the at least one counter electrode 126.
A further hydrophobic region 128 may be arranged between the counter electrode(s) 126 and the transportation path 104.
The further hydrophobic region 128 may be formed from any suitable hydrophobic material, such as a chloropolymer and/or a fluoropolymer, for example CYTOP^® and/or Fluoropel, as described above in relation to the hydrophobic region 122.
One or more (further) layers of dielectric material, such as one or more of a parylene layer, a tantalum pentoxide layer and a silicon nitride layer, may be interposed between the counter electrode(s) 126 and the further hydrophobic region 128, similarly to the above-described layer(s) of dielectric material that may be present between the plurality of electrodes 102 and the hydrophobic region 122.
The at least one counter electrode 126 may be provided/formed in any suitable manner. In some embodiments, such as that shown in FIGs. 1A to 1D, the at least one counter electrode 126 comprises, e.g. is in the form of, a conductive layer, for example an indium tin oxide layer. In such embodiments, the further hydrophobic region 128 may be interposed between the conductive layer and the transportation path 104.
In some embodiments, such as that shown in FIGs. 1A to 1D, the transportation path 104 extends along a channel defined between opposing substrate portions 130, 132.
In such embodiments, each of the hydrophobic region 122 and the further hydrophobic region 128 may be exposed to a channel provided between a substrate portion 130 and a further substrate portion 132, along which channel at least part of the transportation path 104 extends.
In some embodiments, the hydrophobic region 122 may be an integral part of the substrate portion 130, provided that the substrate portion 130 is formed from a hydrophobic material.
Alternatively or additionally, the further hydrophobic region 128 may be an integral part of the further substrate portion 132, provided that the further substrate portion 132 is formed from a hydrophobic material.
More generally, each of the at least one counter electrode 126 may be connected to ground 112, as shown in FIGs. 1A to 1D.
The single counter electrode 126, e.g. conductive layer, shown in FIGs. 1A to ID may represent a relatively straightforward way of implementing the at least one counter electrode 126, although any number of counter electrode(s) 126 can be contemplated.
In some embodiments, such as that shown in FIGs. 1A to 1D, the first power supply 110 comprises, e.g. is defined by, a first alternating current power supply whose peak-to-peak amplitude voltage is in the range of 25 to 100 V, preferably in the range of 70 to 90 V, such as about 80 V.
Such a peak-to-peak amplitude voltage may provide a sufficiently strong electric field for implementing the electrowetting transportation of sweat droplets whilst not being so high so as to compromise practical application of the electrowetting apparatus 100, e.g. in a wearable sweat sampling device.
Alternatively or additionally, a supply voltage frequency of the first alternating current power supply may be in the range of 500 to 1500 Hz, such as about 1000 Hz. Such a supply voltage frequency has been found to provide efficient charging of the electrodes 102, and concomitant effective sweat droplet 124 transportation.
In a non-limiting illustrative example, the peak-to-peak amplitude voltage of the first alternating current power supply included in, e.g. defining, the first power supply 110 is about 80 V, and the supply voltage frequency of the first alternating current power supply is about 1000 Hz.
Charging of each of the electrodes 102 may require less than 10 ms, for example less than 1 ms.
The switching system 108A, 108B, 108C, 108D, 108E may be configured such that the sweat droplet 124 migrates, in other words "flips", from one electrode 102 to a successive electrode 102 in 1 to 500 ms, depending on air or oil in the channel 104. Typically, in air less than 10 ms.
In some embodiments, such as that shown in FIGs. 1A to 1D, the plurality of electrodes 102 comprises three or more sets of electrodes 102, with each set having two or more electrodes 102. The switching system 108A, 108B, 108C, 108D, 108E may accordingly include a switching element 108A, 108B, 108C, 108D, 108E, e.g. relay, for each of the sets of electrodes 102, with each switching element 108A, 108B, 108C, 108D, 108E being configured to enable switching of a respective set of electrodes 102 from being connected to the first terminal of the first power supply 110 to being disconnected from the first terminal of the first power supply 110.
In such embodiments, only the electrodes 102 of a given set may be connected to each other, without electrical connections being present between electrodes 102 that respectively belong to different sets. Such sets of electrodes 102, with the switching element 108A, 108B, 108C, 108D, 108E, e.g. relay, for each set may assist to reduce a number of electrical connections between the plurality electrodes 102 and the switching system 108A, 108B, 108C, 108D, 108E relative to, for example, a scenario in which each electrode 102 of the plurality of electrodes 102 were to be individually controlled.
In some embodiments, such as that shown in FIGs. 1A to 1D, the plurality of electrodes 102 comprises five sets of electrodes 102. As shown in FIGs. 1A to 1D, the electrodes 102 numbered "1" correspond to a first set of electrodes 102 that is connected to and disconnected from the first terminal of the first power supply 110 via the switching element 108A, the electrodes 102 numbered "2" correspond to a second set of electrodes 102 that is connected to and disconnected from the first terminal of the first power supply 110 via the switching element 108B, the electrodes 102 numbered "3" correspond to a third set of electrodes 102 that is connected to and disconnected from the first terminal of the first power supply 110 via the switching element 108C, the electrodes 102 numbered "4" correspond to a fourth set of electrodes 102 that is connected to and disconnected from the first terminal of the first power supply 110 via the switching element 108D, and the electrodes 102 numbered "5" correspond to a fifth set of electrodes 102 that is connected to and disconnected from the first terminal of the first power supply 110 via the switching element 108E. In such embodiments, the number of electrical connections between the plurality electrodes 102 and the switching system 108A, 108B, 108C, 108D, 108E is five.
It is noted, for the avoidance of doubt, that the five sets of electrodes 102 in FIGs. 1A to ID is to provide an illustration of the principle, and any number of sets of electrodes 102 can be contemplated, such as two, three, four, six, seven, eight, nine, ten, and so on.
Whilst four electrodes 102 are included in each of the five sets shown in FIGs. 1A to 1D, this is also only for the purpose of illustration. In some embodiments, eight electrodes 102 to four hundred electrodes 102 may be included in each set, in other words eight electrodes 102 to four hundred electrodes 102 may have the same number: "1", "2", "3", etc.
In embodiments, such as that shown in FIGs. 1A to 1D, in which the counter electrode(s) 126 is or are included in the electrowetting apparatus 100, further electrical connection(s) is or are required to connect each of the counter electrode(s) 126 to the electrowetting transport control circuit 106.
In the illustrative non-limiting example shown in FIGs. 1A to 1D, one additional electrical connection to the single counter electrode 126 is provided (in addition to the above-mentioned five electrical connections connecting the five sets of electrodes 102 to the switching system 108A, 108B, 108C, 108D, 108E).
It is desirable to detect the presence of a sweat droplet 124 on the transportation path, for example for the purpose of counting such detected sweat droplets 124 produced over time in order to estimate a sweat rate per sweat gland. Moreover, providing such droplet presence detection functionality using the electrodes 102 already provided for electrowetting transportation may provide various advantages, including a simpler physical design in which requirement for a dedicated droplet sensor in addition to the electrodes 102 is obviated.
To this end, the electrowetting apparatus 100 shown in FIGs. 1A to ID comprises a sensing circuit 134 for providing, via connection of the sensing circuit 134 with at least one electrode 136 of the plurality of electrodes 102, an electrical signal indicative of droplet presence on the transportation path 104.
Any suitable sensing principle may be employed in order for the sensing circuit 134 to provide the electrical signal indicative of droplet presence on the transportation path 104. Particular mention is made of capacitive droplet sensing.
When a droplet 124 passes two electrically isolated electrodes 126, 136 a dielectric value is changed therebetween given that air and moisture, e.g. sweat, have different dielectric values from each other. Such a change in dielectric value is detectable, thereby enabling, for instance, counting of sweat droplets 124, and in certain embodiments determination of the volume of each sweat droplet 124 (as will be explained herein below). Thus, even relatively low sweat rates may be measurable.
Such capacitive droplet sensing by the sensing circuit 134 may also be particularly suitable in the context of transportation via electrowetting, given the associated electrical isolation of the electrodes 102 from the sweat droplet owing to the hydrophobic region 122 and/or dielectric layer(s) between each of the electrodes 102, 126 and the transportation path 104.
In some embodiments, such as that shown in FIGs. 1A to 1D, the electrical signal is indicative of a capacitance between the at least one electrode 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) and the at least one counter electrode 126 spaced apart from the at least one electrode 136.
The sensing circuit 134 may include a second power supply 138.
In some embodiments, such as that shown in FIGs. 1A to 1D, the second power supply 138 comprises, e.g. is defined by, a second alternating current power supply whose peak-to-peak amplitude voltage is in the range of 1 to 20 V, preferably in the range of 5 to 15 V, such as about 10 V.
Such a peak-to-peak amplitude voltage has been found to be low enough to minimize the risk of the sensing circuit 134 causing migration of the sweat droplet 124 whose presence is being detected, whilst high enough to facilitate sensing, e.g. capacitive sensing, of such a sweat droplet 124.
More generally, the peak-to-peak amplitude voltage provided by the first alternating current power supply may be different from that of the second alternating current power supply. Thus, the peak-to-peak amplitude voltage may be appropriately selected according to the electrowetting transportation functionality of the electrowetting transport control circuit 106 and according to the droplet presence sensing functionality of the sensing circuit 134. Preferably, the peak-to-peak amplitude voltage, e.g. in the range of 25 to 100 V, provided by the first alternating power supply is higher than that provided by the second alternating power supply, e.g. 1 to 20 V.
In some embodiments, a supply voltage frequency of the second alternating current power supply may be in the range of 2000 to 8000 Hz, preferably in the range of 3000 to 7000 Hz, such as about 5000 Hz. Such a supply voltage frequency has been found to facilitate capacitive sensing of sweat droplets 124.
In a non-limiting illustrative example, the peak-to-peak amplitude voltage of the second alternating current power supply included in, e.g. defining, the second power supply 138 is about 10 V, and the supply voltage frequency of the second alternating current power supply is about 5000 Hz.
In a further non-limiting example, the peak-to-peak amplitude voltage of the first alternating current power supply included in, e.g. defining, the first power supply 110 is about 80 V, and the supply voltage frequency of the first alternating current power supply is about 1000 Hz, with the peak-to-peak amplitude voltage of the second alternating current power supply included in, e.g. defining, the second power supply 138 being about 10 V, and the supply voltage frequency of the second alternating current power supply being about 5000 Hz.
In such an example, the charging of an electrode 102 may require less than 1 ms, and 10 ms may be used for gathering the electrical signal(s). Typically, a sweat droplet 124 may migrate to a successive electrode 102 in 1 to 500 ms, depending on air or oil in the channel 104. Typically, in air less than 10 ms.
More generally, the supply voltage frequency provided by the first alternating current power supply may be different from that of the second alternating current power supply. Thus, the supply voltage frequency may be appropriately selected according to the electrowetting transportation functionality of the electrowetting transport control circuit 106 and according to the droplet presence sensing functionality of the sensing circuit 134. Preferably, the supply voltage frequency, e.g. in the range of 500 to 1500 Hz, provided by the first alternating power supply is lower than that provided by the second alternating power supply, e.g. 2000 to 8000 Hz.
It is noted that the terms "first" and "second" in the context of the first power supply 110 included in the electrowetting transport control circuit 106 and the second power supply 138 included in the sensing circuit 134 respectively are used to distinguish between the power supplies 110, 138 provided for each of these circuits 106, 134. It is nonetheless noted that in alternative embodiments a single power supply (not visible) could conceivably be employed instead of the first power supply 110 and the second power supply 138 being both included in the electrowetting apparatus 100.
Various challenges have been encountered in using the electrodes 102 and such a sensing circuit 134 to provide the droplet presence detection functionality. In particular, severe background noise from the electrowetting transport control circuit 106 may hamper detection of relatively weak electrical signals associated with the presence of a sweat droplet 124. Moreover, droplet presence detection may be hampered by movement of the sweat droplet 124 by the electrowetting transport control circuit 106 away from the at least one electrode 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) before the sensing circuit 134 has been able to provide an electrical signal that is reliably indicative of the presence, or otherwise, of a sweat droplet 124.
For these reasons, and referring again to FIGs. 1A to 1D, a switch 140 is configured to enable switching between the at least one electrode 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) being connected to and disconnected from the electrowetting transport control circuit 106. The capability to disconnect the at least one electrode 136 from the electrowetting transport control circuit 106 may assist to reduce interference with the electrical signal by noise associated with the electrowetting transport control circuit 106, thereby enabling discernment of relatively small signal differences.
In this respect, the capacitance of a capacitor formed by the electrode(s) 136 and the counter electrode(s) 126 may be in the range 1 to 100 pF, such as typically about 2.5 pF. The difference in this typical value is in the order of about 0.5 pF between air and sweat. This is a relatively small value and noise may obscure the difference between air and a sweat droplet 124 being between the electrically isolated electrodes 126, 136. However, this noise may be decreased by controlling the switch 140 to isolate the electrode(s) 136 from the electrowetting transport control circuit 106.
Moreover, the switch 140 may also enable, in some embodiments, the sweat droplet 124 to be immobilized adjacent the at least one electrode 136 so that the electrical signal can be more reliably indicative of the presence, or otherwise, of a sweat droplet 124.
Referring again to FIG. 1B, the sweat droplet 124 is adjacent the electrode 102 numbered "4" towards the right hand side of the transportation path 104, which also happens to be the at least one electrode 136 whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal. In FIG. 1B the position of the switch 140 is such that the electrode(s) 136 is or are still connected to the electrowetting transport control circuit 106. However, in FIG. 1C the position of the switch 140 is changed to a position in which the electrode(s) 136 is or are disconnected from the electrowetting transport control circuit 106. This may reduce interference with the electrical signal by noise associated the electrowetting transport control circuit 106, as previously described.
Moreover, the lower peak-to-peak amplitude voltage, e.g. 1 to 20 V, provided by the second alternating current power supply may be sufficiently low to minimize the risk of the sensing circuit 134 causing migration of the sweat droplet 124 still at the position of the neighboring electrode numbered "3" or at the position of the successive electrode numbered "5". Hence, the position of the sweat droplet 124 may be maintained until the electrode(s) 136 is or are connected again to the electrowetting transport control circuit 106, at which point the sweat droplet 124 may again migrate along the transportation path 104.
It is noted that the droplet migration shown in FIG. ID is implemented via the switching element 108E, e.g. relay, connecting each of the electrodes 102 numbered "5", in other words each of the electrodes 102 belonging to that set, to the first terminal of the first power supply 110.
In some embodiments, the switch 140 is configured to enable switching between a first configuration in which the at least one electrode 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) is connected to the electrowetting transport control circuit 106 and is disconnected from the sensing circuit 134, as shown in FIGs. 1A, 1B and 1D, and a second configuration in which the at least one electrode 136 is connected to the sensing circuit 134 and is disconnected from the electrowetting transport control circuit 106, as shown in FIG. 1C. This may provide particularly convenient switching operation, since the at least one electrode's 136 connection to and disconnection from the sensing circuit 134 may be respectively accompanied, e.g. automatically, by disconnection from and connection to the electrowetting transport control circuit 106.
The switch 140 can be implemented in any suitable manner. For example, the switch 140 may comprise a relay.
In embodiments, such as that shown in FIGs. 1A to 1D, in which the electrowetting transport control circuit 106 is configured to implement the charging and discharging of the plurality of electrodes 102 by controlling an electric field between each of the plurality of electrodes 102 and the at least one counter electrode 126, the electrowetting apparatus 100 may include a further switch 142 configured to enable switching between the at least one counter electrode 126 being connected to and disconnected from the electrowetting transport control circuit 106. This may further assist to reduce interference with the electrical signal by noise associated with the electrowetting transport control circuit 106.
The further switch 142 can be implemented in any suitable manner. For example, the further switch 142 may comprise a relay.
The further switch 142 may be configured to enable switching between a first configuration in which the at least one counter electrode 126 is connected to the electrowetting transport control circuit 106 and is disconnected from the sensing circuit 134, as shown in FIGs. 1A, 1B and 1D, and a second configuration in which the at least one counter electrode 126 is connected to the sensing circuit 134 and is disconnected from the electrowetting transport control circuit 106, as shown in FIG. 1C.
This may provide particularly convenient switching operation, since the at least one counter electrode's 126 connection to and disconnection from the sensing circuit 134 may be respectively accompanied, e.g. automatically, by disconnection from and connection to the electrowetting transport control circuit 106.
In some embodiments, such as that shown in FIGs. 1A to 1D, the switch 140 is controllable such that the electrode(s) 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) is or are disconnected from the electrowetting transport control circuit 106 while the further switch 142 is controllable such that the counter electrode(s) 126 is or are disconnected from the electrowetting transport control circuit 106.
For example, the first configuration of the switch 140 is selectable at the same time as the first configuration of the further switch 142, and the second configuration of the switch 140 is selectable at the same time as the second configuration of the further switch 142.
Such selection of the configurations of the switch 140 and the further switch 142 may be implemented via processor(s) configured to control the switch 140 and the further switch 142, as described herein below with reference to FIG. 3.
In embodiments, such as that shown in FIGs. 1A to 1D, in which the plurality of electrodes 102 include the sets of electrodes 102, the at least one electrode 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) may comprise, or in some embodiments consist of, a single electrode 136 of one of the sets of electrodes 102. This may assist to mitigate the risk of an electrical signal deriving from one of the electrodes 102 of a given set to which a sweat droplet 124 is adjacent being rendered unmeasurable by electrical signals deriving from the other electrodes 102 of the set to which no sweat droplet 124 is adjacent, noting the relatively small capacitance difference between the sweat droplet 124 and air.
Moreover, it may well be the case that a sweat droplet 124 is located adjacent more than one electrode 102 of the set, such that the at least one electrode 136 comprising only a single electrode 136 of the set may assist to avoid signal confusion associated with several sweat droplets 124 being respectively adjacent electrodes 102 of the same set, once again noting that eight electrodes 102 to four hundred electrodes 102 may be included in each set.
Measuring a change in voltage arising from the presence of the sweat droplet 124 may necessitate a relatively large resistor to pick up such a voltage signal, and this may also create a relatively large impedance that may cause increased electrical noise pickup. In some embodiments, such as that shown in FIGs. 1A to ID and 2, the sensing circuit 134 comprises a transimpedance amplifier 144 arranged to convert a current in the sensing circuit 134 to a voltage output, V_out. The transimpedance amplifier 144 may enable measurement of the electrical current with a relatively low impedance electrical circuit (due to the above-mentioned relatively large resistor being obviated), thereby minimizing pickup of environmental electrical noise.
An additional advantage may be that the distance between the electrodes 102 and the transimpedance amplifier 144 can be relatively large, and therefore no electrical amplification may be required to be implemented on a sweat sampling device, e.g. a wearable sweat sampling device. Rather, the electrical amplification may be instead located in a separate acquisition device. This can make product development easier, for instance without having to incorporate electrical amplification in a wearable sweat sampling device, e.g. via an application-specific integrated circuit (ASIC) included in the wearable sweat sampling device, e.g. an on-sweat patch ASIC.
In such embodiments, the V_out of the transimpedance amplifier 144 may be proportional to a value of the alternating current present between the electrode(s) 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) and the counter electrode(s) 126.
In some embodiments, such as that shown in FIGs. 1A to 1D and 2, the sensing circuit 134, e.g. the transimpedance amplifier 144 included in the sensing circuit 134, includes an operational amplifier 146. It is noted that the power supply lines to the operational amplifier 146 depicted in FIGs. 1A to 1D and 2 have not been drawn.
Any suitable type of operational amplifier 146 can be contemplated. Particular mention is made of an operational amplifier 146 with a low input bias current. A non-limiting example of the latter is a TL072CP operational amplifier from Texas Instruments.
In some embodiments, such as that shown in FIGs. 1A to 1D and 2, the transimpedance amplifier 144 comprises a capacitor 148 in parallel with a feedback resistor 150 of the transimpedance amplifier 144. The feedback resistor 150 in combination with the capacitor 148 may form a first frequency filter.
Such a capacitor 148 may, for example have a capacitance in the range of 100 to 1000 pF, such as about 300 pF.
Alternatively or additionally, the resistance of the feedback resistor 150 may be in the range of 300 to 600 kQ, such as about 470 kQ.
It is noted that in the non-limiting example shown in FIGs. 1A to 1D, the resistance of all of the resistors 114A, 114B, 114C, 114D, 114E and the feedback resistor 150 may be in the range of 300 to 600 kQ, such as about 470 kQ.
In some embodiments, such as that shown in FIG. 3, the electrowetting apparatus 100 comprises one or more processors 152 configured to control the switch 140 to switch between the at least one of the plurality of electrodes 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) being connected to and disconnected from the electrowetting transport control circuit 106. Control signal(s) for controlling the switch 140 is or are schematically represented in FIG. 3 by the arrow extending from the block denoting the processor(s) 152 to the block denoting the switch 140.
In some embodiments, such as that shown in FIG. 3, the one or more processors 152 is or are configured to control the further switch 142 to switch between the at least one counter electrode 126 being connected to and disconnected from the electrowetting transport control circuit 106. Control signal(s) for controlling the further switch 142 is or are schematically represented in FIG. 3 by the arrow extending from the block denoting the processor(s) 152 to the block denoting the further switch 142.
Alternatively or additionally, the processor(s) 152 may be configured to obtain the electrical signal while the at least one electrode 136 (whose connection with the sensing circuit 134 enables the sensing circuit 134 to provide the electrical signal) is disconnected from the electrowetting transport control circuit 106. The electrical signal being obtained by the processor(s) 152 is schematically represented in FIG. 3 by the arrow extending from the block denoting the sensing circuit 134 to the block denoting the processor(s) 152.
For example, the one or more processors 152 comprises: a first processor configured to control the switch 140 to switch between said at least one electrode 136 being connected to and disconnected from the electrowetting transport control circuit 106, and optionally to control the further switch 142 to switch between said at least one counter electrode 126 being connected to and disconnected from the electrowetting transport control circuit 106; and a second processor configured to obtain the electrical signal while said at least one electrode 136 is disconnected from the electrowetting transport control circuit 106.
The first processor may also control the switching system 108A, 108B, 108C, 108D, 108E.
In some embodiments, the one or more processors 152 is or are configured to obtain the electrical signal from the sensing circuit 134 as an electrical signal as a function of time, and transform the electrical signal as a function of time to an electrical signal as a function of frequency.
Such a transform, for example Fourier transform, may provide a filter for significant improvement in noise reduction. The Fourier transform may provide a relatively high-quality filter.
In embodiments in which the sensing circuit 134 includes the transimpedance amplifier 144, the V_out of the transimpedance amplifier 144, in the form of a voltage output as a function of time, may be fed into an algorithm executing the Fourier transform. Such an algorithm may be run on the processor(s) 152, e.g. on a processor included in a computer that receives the raw data in a digitized format from an analogue to digital converter.
As an alternative to the Fourier transform, the electrowetting apparatus 100 may include a lock-in amplifier (not visible in the Figures).
Such a lock-in amplifier enables selection of a certain frequency that is to be observed, and enables measurement of both the amplitude and the phase shift (with respect to the original AC signal as produced by the AC source, in other words the second alternating current power supply). The measured amplitude corresponds to the resistance, and the phase shift corresponds to the capacitance.
It is noted that, as well as enabling counting of sweat droplets 124, the electrowetting apparatus 100 may enable a measure of a volume of a sweat droplet 124 to be extracted from the electrical signal.
By counting the sweat droplets 124 the sweat rate in the channel between the substrate portion 130 and the further substrate portion 132 may be determinable. Moreover, an electrical signal resulting from a sweat droplet 124 that is partially overlapping with the isolated electrodes 126, 136 may be measured, followed by measurement of an electrical signal resulting from a sweat droplet 124 that fully covers the isolated electrodes 126, 136, and subsequently measurement of an electrical signal resulting from again the sweat droplet 124 that is partially overlapping with the isolated electrodes 126, 136 during movement of the sweat droplet 124 along the transportation path 104.
The capacitance value during the partial overlap may contain the information on the volume of the droplet 124.
Whilst the manner in which the sweat droplets 124 are formed may be designed to obtain sweat droplets 124 of a uniform volume, some variation in volume may nonetheless arise. Moreover, two sweat droplets 124 may merge along the transportation path 104. Hence part of the present disclosure concerns measurement of the droplet volume.
In some embodiments, the droplet volume measurement comprises continuously calibrating the measured value for the sweat droplet 124 with the electrodes 126, 136 by measuring electrical signal when the isolated electrodes 126, 136 are fully covered by a sweat droplet 124. The latter should be a constant value, however it is known that measurement between two electrowetting electrodes 126, 136 is not fully an ideal capacitor since it also contains a, although high, electrical resistance value (in the order of megaohms) and it is known that there is a drift in this resistance value. Since the isolated electrodes 126, 136 fully covered by a droplet 124 should give the same value, the measurement in the case of the isolated electrodes 126, 136 being partially covered by a droplet 124 may be calibrated.
Alternatively, or additionally, an external capacitor may be provided over the two electrodes 126, 136. In such embodiments, the resultant high pass filter may enable measurement on the plateau (the region where the signal is independent of the applied frequency), thereby rendering the measurement independent of drift in the resistance value.
More generally, and referring again to FIG. 3, the one or more processors 152 may be configured to extract a measure of a volume of a sweat droplet 124 from the electrical signal.
The description provided above has focused on the design of the electrowetting apparatus 100. The following description is provided for explaining sampling of sweat.
FIG. 4 schematically depicts, in cross-sectional view, part of a sweat sampling apparatus 200 according to an example. The sweat sampling apparatus 200 may include the electrowetting apparatus 100 according to any of the embodiments described herein.
The sweat sampling apparatus 200 comprises a chamber 202 having an inlet 204. The inlet 204 receives sweat from the skin 206. As shown in FIG. 4, the inlet 204 may be disposed adjacent to a surface of the skin 206. Whilst a single chamber 202 is depicted in FIG. 4, this is not intended to be limiting, and in other examples a plurality of chambers 202 may be included in the sweat sampling apparatus 200, as will be further described herein below.
The inlet 204 is shown proximal to a sweat gland 208. In this case, the sweat excreted by the sweat gland 208 enters and fills the chamber 202 via the inlet 204. As shown in FIG. 4, the sweat sampling apparatus 200 may comprise a substrate 210 which is attached to the surface of the skin 206. In the depicted example, a lower surface of the substrate 210 is in direct contact with the surface of the skin 206. In this case, the chamber 202 takes the form of an aperture delimited by the substrate 210. The substrate 210 may be formed of any suitable material, e.g. a polymer, capable of being disposed on the skin. For example, the substrate 210 may have at least a degree of flexibility so as to enable conformal application to the surface of the skin 206. More rigid substrates 210 may also be contemplated, providing the inlet 204 can receive sweat from the skin 206.
It is noted that the further substrate portion 132 described above in relation to the electrowetting apparatus 100 may be included in the substrate 210.
In order to collect sweat from a subject, the substrate 210 may, for instance, be adhered to the surface of the skin 206 using a suitable biocompatible adhesive. Alternatively, the substrate 210 may be held against the surface of the skin 206 by fastenings, e.g. straps, for attaching the substrate 210 to the body of the subject.
In some embodiments, each inlet 204 of the plurality of chambers 202 is dimensioned to receive sweat from, on average, 0.1 to 1 active sweat glands. This may assist the sweat sampling apparatus 200 to be used for determination of the sweat rate per sweat gland.
It is preferable that the diameter of the inlet 204 for receiving sweat from the skin 206 is selected to be relatively small, for example 200-2000 µm, such as 300-1200 µm, e.g. about 360 µm or about 1130 µm. The diameter of sweat gland outlets on the surface of the skin 206 are typically in the range of about 60 µm to 120 µm. A relatively small inlet 204 may assist to reduce the chances of two or more sweat glands 208 excreting into the same inlet 204, which can complicate interpretation of the electrical signals. To compensate for the limited amounts of sweat being received into an individual chamber 202, the apparatus 200 may, for instance, include a plurality of such chambers 202, for example 2 to 50 chambers 202, such as 10 to 40 chambers 202, e.g. about 25 chambers 202.
Once the chamber 202 has been filled with sweat, a sweat droplet 124 protrudes from an outlet 214 of the chamber 202. In the example shown in FIG. 4, the outlet 214 is delimited by an upper surface of the substrate 210, and a hemispherical sweat droplet 124 forms on top of the outlet 214 once the chamber 202 has been filled with sweat.
More generally, the sweat sampling apparatus 200 may be configured such that the speed of formation of the sweat droplet 124 is determined by the sweat rate, while the volume of the sweat droplet 124 is determined by the electrowetting apparatus 100. This will be explained in further detail herein below.
The respective areas of the inlet 204 and the outlet 214 may be selected to ensure efficient filling of the chamber 202 and sweat droplet 124 formation over a range of sweat rates.
Each inlet 204 may, for example, have an area between 0.005 mm² to 20 mm².
In some examples, the inlet 204 and the outlet 214 have selected fixed dimensions for this purpose. Alternatively, the apparatus 200 may be configurable such that at least some of the dimensions and geometry relevant to sweat droplet 124 formation can be varied.
In a preferred example, the chamber 202 is dimensioned to fill up with sweat within 10-15 minutes. The formation of the hemispherical sweat droplet 124 following filling of the chamber 202 preferably occurs typically within 10 seconds at relatively low sweat rate, e.g. 0.2 nl/min/gland.
The diameter of the outlet 214 may, for example, be in the range of 10 µm to 100 µm, e.g. 15 µm to 60 µm, such as about 33 µm, in order to assist in controlling the sweat droplet 124 size so that its volume is uniform and reproducible. By the outlet 214 having such a diameter, e.g. about 33 µm, several sweat droplets 124 may be formed during a single sweat burst (typically lasting 30 seconds) of a sweat gland 208, even with sweat rates as low as 0.2 nl/min/gland. Consequently, sufficient sweat droplets 124 may be generated and transported by the sweat sampling apparatus 200 in order for the sweat rate to be reliably estimated.
As an indication of the scale of the part of the exemplary sweat sampling apparatus 200 shown in FIG. 4, the length 216 (denoted by the double-headed arrow) is about 500 µm. More generally, the dimensions of the chamber 202, inlet 204, and outlet 214 may be selected according to, for instance, the sweat rate of the subject. The volume of the chamber 202 may be minimized in order to decrease the filling time. This may assist to ensure a minimal delay between actual sweat excretion and sensing/monitoring of the sweat droplets 124. For example, the volume of the chamber 202 may be in the range of 0.1-100 nl, such as 0.5-50 nl, e.g. 1-20 nl.
The volume of the chamber 202 may be minimized in various ways in order to minimize the time required to fill the chamber 202 with sweat. Such modifications may be, for instance, to the substrate 210 delimiting the chamber 202.
FIG. 4 shows an example in which the chamber 202 tapers from the inlet 204 towards the outlet 214. The volume of such a tapering chamber 202 will be less than, for example, a cylindrical chamber 202 having the same height and base diameter dimensions.
By illustration, the length dimension 216 of the substrate 210 shown in FIG. 4 is about 500 µm, and the tapering chamber 202 in this example has a conical geometry, i.e. having a truncated cone shape with a volume of 1/3πh[R² + Rr + r²] (h = 50 µm; R = 360 µm; r = 33 µm). For a relatively low sweat rate of 0.2 nl/min/gland, the filling time of this tapering chamber 202 may be about 10 minutes and the sweat droplet 124 formation may take around 12 seconds. By contrast, filling of a cylindrical chamber 202 having the same height (50 µm) and base (360 µm) dimensions may take around 50 minutes, and the formation time of the hemispherical sweat droplet 124 may be more than 3 hours.
At this point it is noted that sweat glands 208 tend to excrete in sweat bursts, each sweat burst being followed by a rest period in which the glands 208 are not excreting. During the sweat burst period the sweat rate may be about six times larger than the average sweat rate. The reason is that in a time window of 180 seconds there is typically a sweat burst of 30 seconds and a rest period of typically 150 seconds, hence there is a factor of six between the average sweat rate and the sweat rate during a sweat burst. In the above illustrative example of a chamber 202 having a truncated conical shape, the time to form the depicted sweat droplet 124 is about 12 seconds during the sweat burst of the sweat gland 208.
As an alternative or in addition to the tapering shape of the chamber 202 to minimize its volume, chamber 202 may be partitioned into compartments, with at least some of the compartments being fluidly connected to each other in order to permit the chamber 202 to be filled with sweat. Such compartments may be formed by pillars. Such pillars may form part of the substate 210, and in such an example may be formed by patterning, e.g. etching, the lower surface of the substrate 210. Other suitable ways of forming such pillars will be readily apparent to the skilled person.
A porous material, e.g. a frit-like material, such as a sintered glass material, may partition the chamber 202 into compartments. The volume of the chamber 202 may be decreased due to the space occupied by the partitions between the pores of the porous material. Depending on the shape of the chamber 202, and the degree to which the material partitioning the pores occupies the chamber 202, the filling time of the chamber 102 may be, for instance, reduced by to 1-4 minutes.
The porous material may further serve as a filter for species, such as aggregated proteins, which may otherwise block downstream components of the sweat sampling apparatus 200, such as the outlet 214 or the transportation path 104 of the electrowetting apparatus 100. In addition, the porous material may assist to prevent fouling of the sweat sampling apparatus 200 by certain sweat components and impurities. The porous material may, for instance, be selected to have specific adsorption properties for proteins and other species which it may be desirable to remove from the sweat entering or being contained within the chamber 202. Removing such impurities may be advantageous due to lessening the risk of the impurities altering the surface properties in the electrowetting apparatus 100, e.g. due to adsorption onto a surface of the electrowetting apparatus 100, such as on the surface of the hydrophobic region 122 and/or the further hydrophobic region 128. Thus, the porous material may assist to mitigate the risk that such impurities impair the hydrophilic/hydrophobic balance required for release of the sweat droplets 124 from the outlet 214, and downstream migration of the sweat droplets 124.
In examples where the porous material comprises, or is, an incompressible frit-like material positioned adjacent the surface of the skin 206, the porous material may prevent, partly due to its incompressibility, blockage by bulging of skin 206 into the chamber 202.
The diameter of the pores of the porous material may be, for instance, in the range of 100 nm to 10 µm. The diameter of the partitions between the pores may also, for instance, be in the range of 100 nm to 10 µm, in order to minimize the risk that such partitions themselves block the exit of a sweat gland 208. In this respect, the exit diameter of sweat glands 208 is typically in the range of about 60 µm to 120 µm.
In at least some embodiments, such as that shown in FIG. 4, sweat droplet 124 detachment is effected via electrowetting. In such embodiments, the upper surface of the substrate 210 is provided with electrodes 102 of the electrowetting apparatus 100. Detachment from the outlet 214 may occur when the sweat droplet 124 has grown to acquire a sufficiently large diameter that the sweat droplet 124 at least partially overlaps a pair of consecutive electrodes 102. In this case, once an electrowetting wave passes along the electrodes 102, the sweat droplet 124 spanning the pair of consecutive electrodes 102 may be dislodged from the outlet 214 accordingly. The direction of transport along the transportation path 104 is denoted in FIG. 4 by the arrow 226. In this example, the sweat droplets 124 may not be all of a uniform size or volume, because the sweat droplet 124 may continue to grow to varying degrees in the period between the sweat droplet 124 reaching the requisite diameter and the arrival of the electrowetting wave. In this respect, the sweat droplet 124 size may be determined by the frequency of the electrowetting wave.
In some embodiments, such as that shown in FIG. 5, the sweat sampling apparatus 200 comprises a substrate 228 which is separated from and opposes the substrate 210 delimiting the chamber 202. The substrate 228 may enable control to be exerted over the volume of the sweat droplet 124. This may be achieved, for instance, by the substrate 228 being separated from the substrate 210 by a defined distance 230. The sweat droplet 124 may increase in size until it makes contact with the substrate 228. In practice, when the sweat droplet 124 contacts the substrate 228, the sweat droplet 124 may become detached by "jumping" over to the substrate 228.
The separation distance 230 between the substrate 210 and the opposing substrate 228 may be selected such that it is large enough to ensure that the diameter of the forming sweat droplet 124, e.g. hemispherical sweat droplet 124, is sufficiently large before contacting the opposing substrate 228, i.e. the lower surface of the substrate 228 which opposes the upper surface of the substrate 210.
It is noted that the substrate portion 122 described above in relation to the electrowetting apparatus 100 may be included in the substrate 228.
The lower surface of the substrate 228 may be provided with the electrodes 102 of the electrowetting apparatus 100. In this case, migration of the sweat droplet 124 on the substrate 228 via the electrodes 102 may mean that sweat droplet 124 migration may occur when the next electrowetting wave reaches the sweat droplet 124 which has been released onto the substrate 228. Accordingly, a sufficiently high electrowetting wave frequency may ensure transport/migration of sweat droplets 128 of relatively uniform size/volume to the sensor. On the other hand, if the frequency of the electrowetting waves is relatively slow, the size/volume of the sweat droplet 124 may be determined by both the electrowetting wave frequency and the separation 230 of the substrate 210 and the opposing substrate 228, i.e. since the sweat droplet 124 may grow in the period between electrowetting waves.
In some embodiments, the sweat sampling apparatus 200 may be configured to enable control over the separation 230 between the substrate 210 and the opposing substrate 228. This may, for instance, be achieved by the sweat sampling apparatus 200 comprising a mechanism which engages at least one of the substrates 210, 228, which mechanism is configured to move at least one of the substrates 210, 228 such as to adjust the separation 230 of the substrates 210, 228. The control exerted over the mechanism may be manual and/or automatic. Regarding the automatic control, the sweat sampling apparatus 200 may, for example, control the separation 230 according to the sweat rate of the sweat gland 108. In such an example, the sweat sampling apparatus 200 may include a controller configured to control the mechanism to move at least one of the substrates 210, 228 according to a determined sweat rate, e.g. as detected via the processor(s) 152 and the sensing circuit 134. Thus, the sweat sampling apparatus 200 may be configured to control the separation 230 in a dynamic manner.
At relatively high sweat rates the sweat droplet 124 formation may risk being too rapid, and uncontrollable sweat droplet coalescence may occur. This may be mitigated by increasing the separation 230, since it may take a longer time to detach a larger sweat droplet 124 onto the substrate 228.
At relatively low sweat rates, the number of sweat droplets 124 transported to the electrode(s) 136 may be relatively low. This issue may be alleviated by decreasing the separation 230 in order to increase the number of (smaller) sweat droplets 124 formed on the substrate 228.
More generally, migration of a sweat droplet 124 via the electrowetting apparatus 100 may be faster than formation, i.e. the protruding, of the subsequent sweat droplet 124. This is in order to ensure unambiguous sweat droplet definition, i.e. to ensure transport of a train of discrete sweat droplets.
In other words, the electrowetting apparatus 100 may maintain the discrete droplet characteristics of the sweat droplets 124 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 FIGs. 4 and 5, the channel(s) along which the sweat droplets 124 are transported may be at least partially, and preferably fully, enclosed in order to minimize evaporation of the sweat droplets 124 during their transportation along the transportation path 104.
At least part of the sweat sampling apparatus 200, such as the chamber(s) 202 and the electrodes 102 of the electrowetting 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 at least part of the sweat sampling apparatus 200 to a body part such that said inlets 204 receive sweat from the skin 206 of the body part.
At this point it is noted that whilst the counter electrode 126 may be advantageously utilized for both electrowetting transportation and droplet presence detection, as per the embodiment shown in FIGs. 1A to 1D, this is not intended to be limiting. In this respect, and referring to FIG. 6, the electrowetting apparatus 100 may include a (further) counter electrode 250 that does not participate in the transporting of the sweat droplet along the transportation path 104.
In such embodiments, the electrical signal may be indicative of a capacitance between the at least one electrode 136 and the (further) counter electrode 250 spaced apart from the at least one electrode 136.
In embodiments in which the (further) counter electrode 250 is employed for droplet presence detection, the further switch 142 that enables switching between the at least one counter electrode 126 being connected to and disconnected from the electrowetting transport control circuit 106 may be obviated.
In such embodiments, and in the scenario in which the transimpedance amplifier 144 is included in the sensing circuit 134, the (further) electrode 250 may be continuously connected to the negative input of the operation amplifier 146.
Suitable steps may be taken to handle, e.g. dissipate to ground 112, residual charge from the (further) electrode 250 following provision of the electrical signal, as will be readily appreciated by the skilled person.
In other embodiments (not depicted in the Figures), two electrodes 102 of the plurality of electrodes 102 may be employed for the sensing: the electrode 136 and a neighbouring/consecutive electrode 102 along the transportation path 104 with respect to the electrode 136. In such embodiments, the further switch 142, along with the switch 140, may be included to switch between the neighbouring/consecutive electrode 102 being connected to and disconnected from the electrowetting transport control circuit 106.
FIG. 7 provides a flowchart of a method 300 of operating an electrowetting apparatus according to an example. The electrowetting apparatus has a plurality of electrodes arranged to define a transportation path along which sweat droplets are transportable, an electrowetting transport control circuit for charging and discharging the plurality of electrodes in sequence along the transportation path to enable transportation of sweat droplets, a sensing circuit, and a switch.
The electrowetting apparatus being operated in the method 300 may be the electrowetting apparatus 100 according to any of the embodiments described herein.
The method 300 comprises controlling 302 the switch to disconnect at least one electrode of the plurality of electrodes from the electrowetting transport control circuit.
In step 304, an electrical signal is obtained from the at least one electrode, while the at least one electrode is disconnected from the electrowetting transport control circuit. The electrical signal may be indicative of droplet presence, or absence, on the transportation path.
In some embodiments, such as that shown in FIG. 7, the method 300 further comprises controlling 306 the switch to, following the obtaining 304, connect the at least one electrode to the electrowetting transport control circuit. Thus, the migration of droplet(s) along the transportation path can resume.
Further provided is a computer program comprising computer program code which, when executed on one or more processors, causes the one or more processors to perform all of the steps of the method 300. Such processor(s) may, for instance, be the processor(s) 152 included in the electrowetting apparatus 100.
It is noted that for prototyping purposes, an Arduino single-board microcontroller was employed by the inventors to control 302 the switch 140 to switch between said at least one electrode 136 being connected to and disconnected from the electrowetting transport control circuit 106, and to control the switching system 108A, 108B, 108C, 108D, 108E.
A processor included in a computer, separate from the Arduino single-board microcontroller, was employed to obtain 304 the electrical signal, e.g. in the form of raw data in a digitized format from an analogue to digital converter.
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.
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.
Functions implemented by a processor may be implemented by a single processor or by multiple separate processing units which may together be considered to constitute a "processor". Such processing units may in some cases be remote from each other and communicate with each other in a wired or wireless manner.
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.
A computer program may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.
If the term "adapted to" is used in the claims or description, it is noted the term "adapted to" is intended to be equivalent to the term "configured to". If the term "arrangement" is used in the claims or description, it is noted the term "arrangement" is intended to be equivalent to the term "system", and vice versa.
Any reference signs in the claims should not be construed as limiting the scope.

Claims

An electrowetting apparatus (100) for transporting a sweat droplet, the electrowetting apparatus comprising:
a plurality of electrodes (102) arranged to define a transportation path (104) along which the sweat droplet is transportable;

an electrowetting transport control circuit (106) for charging and discharging the plurality of electrodes connected to the electrowetting transport control circuit in sequence along the transportation path to enable the sweat droplet to be transported along the transportation path;

a sensing circuit (134) for providing, via connection of the sensing circuit with at least one electrode (136) of the plurality of electrodes, an electrical signal for indicating droplet presence on the transportation path; and

a switch (140) configured to enable switching between said at least one electrode being connected to and disconnected from the electrowetting transport control circuit.
The electrowetting apparatus (100) according to claim 1, wherein the switch (140) is configured to enable switching between a first configuration in which said at least one electrode (136) is connected to the electrowetting transport control circuit (106) and is disconnected from the sensing circuit (134), and a second configuration in which said at least one electrode is connected to the sensing circuit and is disconnected from the electrowetting transport control circuit.
The electrowetting apparatus (100) according to claim 1 or claim 2, wherein the electrical signal is indicative of a capacitance between the at least one electrode (136) and at least one counter electrode (126; 250) spaced apart from the at least one electrode.
The electrowetting apparatus (100) according to claim 3, wherein the electrowetting transport control circuit (106) is configured to implement said charging and discharging of the plurality of electrodes (102) by controlling an electric field between each of the plurality of electrodes and the at least one counter electrode (126).
The electrowetting apparatus (100) according to claim 3 or claim 4, comprising a further switch (142) configured to enable switching between the at least one counter electrode (126) being connected to and disconnected from the electrowetting transport control circuit (106).
The electrowetting apparatus (100) according to any one of claims 1 to 5, wherein the plurality of electrodes (102) comprises three or more sets of electrodes, with each set having two or more electrodes, and wherein the electrowetting transport control circuit (106) comprises a switching system (108A, 108B, 108C, 108D, 108E) that includes a switching element for each of the sets of electrodes, with each switching element being switchable to enable charging and discharging of a respective set of electrodes.
The electrowetting apparatus (100) according to claim 6, wherein the at least one electrode (136) comprises a single electrode of one of the sets of electrodes (102).
The electrowetting apparatus (100) according to any one of claims 1 to 7, wherein the sensing circuit (134) comprises a transimpedance amplifier (144) arranged to convert a current in the sensing circuit to a voltage output; optionally wherein the transimpedance amplifier comprises a capacitor (148) in parallel with a feedback resistor (150) of the transimpedance amplifier.
The electrowetting apparatus (100) according to any one of claims 1 to 8, comprising one or more processors (152) configured to:
control the switch (140) to switch between said at least one electrode (136) being connected to and disconnected from the electrowetting transport control circuit (106); and/or

obtain the electrical signal while said at least one electrode is disconnected from the electrowetting transport control circuit.
The electrowetting apparatus (100) according to claim 9, wherein the one or more processors (152) is or are configured to:
obtain the electrical signal from the sensing circuit (134) as an electrical signal as a function of time; and

transform the electrical signal as a function of time to an electrical signal as a function of frequency.
The electrowetting apparatus (100) according to claim 9 or claim 10, wherein the one or more processors (152) is or are configured to extract a measure of a droplet volume from the electrical signal.
The electrowetting apparatus (100) according to any one of claims 1 to 11, wherein the electrowetting transport control circuit (106) comprises a first alternating current power supply, and the sensing circuit (134) comprises a second alternating current power supply.
The electrowetting apparatus (100) according to claim 12, wherein a supply voltage frequency of the first alternating current power supply is different from, preferably lower than, that of the second alternating current power supply; and/or wherein a peak-to-peak amplitude voltage provided by the first alternating current power supply is different from, preferably higher than, that of the second alternating current power supply.
A method (300) of operating an electrowetting apparatus having a plurality of electrodes arranged to define a transportation path along which a sweat droplet is transportable, an electrowetting transport control circuit for charging and discharging the plurality of electrodes connected to the electrowetting transport control circuit in sequence along the transportation path to enable transportation of the sweat droplet, a sensing circuit, and a switch, the method comprising:
controlling (302) the switch to disconnect at least one electrode of the plurality of electrodes from the electrowetting transport control circuit; and

obtaining (304), while the at least one electrode is disconnected from the electrowetting transport control circuit, an electrical signal from said at least one electrode for indicating droplet presence on the transportation path; optionally wherein the method further comprises

controlling (306) the switch to, following said obtaining, connect the at least one electrode to the electrowetting transport control circuit.
A computer program comprising computer program code which, when executed on one or more processors, causes the one or more processors to perform all of the steps of the method (300) according claim 14.