Osmotic sweat extraction and sensing system for continuous biomarker monitoring

Abstract

In some example embodiments, there may provided a system that includes an osmotic pump; a fluidics structure coupled to the osmotic pump, and at least one sensor configured to measure a concentration of at least a first analyte in a biofluid collected using the system.

Description

OSMOTIC SWEAT EXTRACTION AND SENSING SYSTEM FOR CONTINUOUS BIOMARKER MONITORINGCross-Reference to Related Application

[0001] This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. provisional patent application number 63 / 568,355, filed on March 21, 2024, and titled “Osmotic Sweat Extraction and Sensing System for Continuous Biomarker Monitoring”, the contents of which are hereby incorporated by reference in their entirety.Technical Field

[0002] The disclosure relates to osmotic sweat extraction and sensing systems for biomarker monitoring.Summary

[0003] In some example embodiments, there is provided a system. The system may include an osmotic pump; a fluidics structure coupled to the osmotic pump, the fluidics structure including a first surface and a second surface distal to the first surface, the fluidics structure having a first end and a second end distal to the first end, the fluidics structure comprising a first portion that extends to a channel portion which extends to a third portion; at least one sensor configured to measure a concentration of at least a first analyte in a biofluid collected using the system; wherein the osmotic pump is disposed on the first surface of the fluidics structure and at the first end of the fluidics structure and at the first portion of the fluidics structure; wherein the osmotic pump is configured to draw the biofluid from a skin surface towards the osmotic pump via the first portion of the fluidics structure through the channel portion where the at least one sensor is disposed; and wherein the second surface of the fluidics structure is configured to be in contact with the skin surface of a wearer of the system to enable the biofluid collection.

[0004] In some variations, a source of power for the system is provided, wherein the source of power includes at least one battery, at least one biofuel cell configured to harvest biofluid from the wearer to provide bioenergy for the system, and / or at least one supercapacitor. The skin surface may be located at a finger and / or a forearm. The biofluid may include sweat and / or an interstitial fluid collected by the fluidics structure from the wearer of the system. The at least one sensor may be a plurality of sensors, each of the plurality of sensors configured to measure acorresponding analyte. The at least one sensor may measure at least the first analyte, wherein the first analyte comprises glucose, lactate, vitamin C, levodopa, sodium, potassium, chloride, calcium, ammonium, alcohol, uric acid, caffeine, proteins, sweat, and / or a sweat rate. The at least one sensor may include at least two electrodes, wherein the at least two electrodes include an anode and a cathode. The at least two electrodes may include a reference electrode. The at least two electrodes may include a conductive current collector. The at least two electrodes include one or more of enzyme, mediator, polymer, surfactant, crosslinker, stabilizer, plasticizer, antibody, aptamers, peptides, molecularly imprinted polymers (MIP), ligands, cells, protein receptor, and / or synthetic receptors. The enzyme may include glucose oxidase, lactate oxidase, uricase, horse radish peroxidase, cholesterol oxidase, polyphenol oxidase, tyrosinase, alcohol oxidase, glucose dehydrogenase, alcohol dehydrogenase, and / or lactate dehydrogenase. The mediator may include ferrocene, quinones, ferricyanide, tetrathiafulvalene, polyoxometalates, nicotinamide adenine dinucleotide (NADH), and / or Prussian blue. The at least one sensor may measure at least the first analyte based on voltammetry, potentiometry, amperometry, and / or impedance, and / or wherein the measurements are processed to determine an estimate of a blood glucose concentration trend or other trend of the first analyte. The osmotic pump may include a gel including at least one polymer or at least one monomer, wherein the gel is treated with a solvent. The polymer may be composed of polyacrylamide, polyvinyl alcohol, alginate, chitosan, hyaluronic acid, collagen, poly(N-isopropylacrylamide), polyethylene oxide, polyacrylic acid, and / or gelatin. The solvent may be composed of water, glycerol, sugar, and / or electrolytes. The fluidics structure may be a paper based material. The fluidics structure is shaped as a serpentine to provide a channel for the biofluid.

[0005] The details of one or more variations of the subject matter described herein are set forth in the accompanying drawings and the description below. Other features and advantages of the subject matter described herein will be apparent from the description and drawings, and from the claims.Brief Description of the Drawings

[0006] The accompanying drawings, which are incorporated in and constitute a part of this specification, show certain aspects of the subject matter disclosed herein and, together with the description, help explain some of the principles associated with the disclosed implementations. In the drawings,

[0007] FIG. 1 illustrates a system disposed on a ventral side of a fingertip, in accordance with some embodiments described herein;

[0008] FIG. 2 illustrates an exploded view of the system, in accordance with some embodiments described herein;

[0009] FIG. 3 illustrates the system disposed on a dorsal side of a fingertip, in accordance with some embodiments described herein;

[0010] FIG. 4 illustrates a flattened, layout view of the system, in accordance with embodiments described herein; and

[0011] FIG. 5 illustrates another example a sensing system, in accordance with some embodiments described herein;

[0012] FIG. 6 depicts an example implementation of a fluidics structure, in accordance with some embodiments described herein; and

[0013] FIG. 7 illustrates another example a sensing system including electrodes, in accordance with some embodiments described herein.Detailed Description

[0014] Practical wearable electronics platforms for non-invasive personal health monitoring may require advanced sensing modalities and highly integrated electronic systems. However, when considering long-term continuous healthcare monitoring, such systems can face limitations due to inadequate energy supply, sensing system capabilities, user experience, intricate circuitry regulation, large device dimensions, and / or the like.

[0015] In some embodiments, there is provided a wearable sweat sensing system that operates on, for example, the skin surface, such as a wearer’s fingertip or other portion of the wearer. This sweat sensing system may be wearable, wireless, energy autonomous, and / or multiplexed. Alternatively, or additionally, the sweat sensing system may utilize a high- efficiency, self-voltage-regulated wearable microgrid power system based on enzymatic biofuel cells and / or batteries to harvest and store energy from natural perspiration without any required body movement or physical exertion. The sweat sensing system may thus operate efficiently at rest.

[0016] The sensing system couples an osmotic pump and a fluidics structure, such as paperbased fluidics, to feed (which may be continuously and / or semi-continuous) a wearer’s naturalfingertip perspiration to a sensor array for sensing including measurement which may be an on- demand, multi-metabolite sweat sensing using the wearer’s perspiration (e.g., sweat). Alternatively, or additionally, the use of low-power electronics for signal acquisition and / or wireless data transmission may enable the sensing system (also referred to herein as an apparatus or sensing apparatus) to be powered wholly (or at least in part) by natural fingertip perspiration, while the sensing system passively detects or measures (e.g., from the collected sweat) glucose, lactate, vitamin C, levodopa, sodium, potassium, chloride, calcium, ammonium, alcohol, uric acid, caffeine, proteins, and / or sweat (as well as levodopa levels within the sweat over time, sweat rate, or other analytes over one or more time periods). The integrated sweat sensing system on for example a fingertip disclosed herein may, in some implementations, provide a solution to effortless, reliable, and / or self-sustainable sweat sensing in a more comprehensive and non- invasive metabolic sensing architecture.

[0017] FIG. 1 illustrates an example of a sensing system 100 from the perspective of a first (e.g., ventral) side of a fingertip of a wearer (e.g., a user), in accordance with some embodiments.

[0018] The sensing system 100 may include an osmotic pump 102, a fluidics structure 104 (also referred to as “fluidics”), and / or at least one sensor 106a. The sensing system 100 operates to extract or collect fluid from a portion of the body (e.g., a finger or other skin surface) of a user or wearer of the sensing system. And, the sensing system’s sensor(s) may be used to detect and / or measure a concentration of at least one analyte in the fluid. For example, the sensing system 100 may be configured to measure the concentration of at least one analyte in fluid extracted from the wearer-user’s body. Examples of analytes include lactate, vitamin C, glucose, L-dopa, and / or the like.

[0019] The osmotic pump 102 may, as noted, be used to extract fluid from a portion of a wearer’s body. For example, the sensing system 100 may be disposed on a fingertip of a user such that the osmotic pump 102 causes the extraction of fluid (e.g., sweat or other biofluid) from the fingertip of the user. The osmotic pump uses osmotic pressure to draw the biofluid, such as sweat, from the fingertip towards the osmotic pump 102, such that the at least one sensor 106a (including its electrodes 108a-d) can detect and / or make measurements on the extracted sweat.

[0020] In some embodiments, there may be a plurality of sensors 106a-e coupled to interconnects 165 that carry the measurements to a circuit board, such as flexible printed circuit board (fPCB) 114. The sensors 106a-d may be disposed on, coupled to, and / or comprise one ormore electrodes 108a-d. In the example of FIG. 1, the electrode 108e is a reference electrode (e.g., a common, a ground and / or the like) shared among electrodes 108a-d to enable measurements.

[0021] Referring again to the osmotic pump 102, it may be coupled to the fluidics structure 104. The fluidics structure 104 may be configured to interface directly with the wearer’s body, such as the skin surface located at the fingertip or other locations (e.g., forearm, etc.). The osmotic pump 102 may be disposed on the fluidics structure 104, such that when the osmotic pump 102 extracts fluid from the body of the user, the fluid enters the fluidics structure 104.

[0022] Moreover, the fluidics structure 104 is coupled to the sensor 106. Fluid that has entered the fluidics structure 104 may be directed (e.g., drawn by osmotic pressure) towards at least one sensor, such as the sensor 106a, so that the sensor can detect and / or make measurements (e.g., measure a concentration of one or more analytes in the fluid, such as sweat).

[0023] In the example of FIG. 1 for example, the fluidics structure 104 has a first surface 180 and a second surface 182 that is distal to the first surface 180. Moreover, the fluidics structure has a first end 192 and a second, opposite end 190 that is distal to the first end. And, the fluidics structure 104 comprises a first portion 195 (e.g., a section) that extends to a channel portion 197, wherein the channel portion extends to a third portion 199 of the fluidics structure 104.

[0024] In some embodiments, at least one sensor 106a may be configured to measure at least a first analyte in a biofluid collected using the sensing system 100. The sensor may be a chemical or biochemical sensor. For example, the sensor 106a (e.g., which may be a chem or biochemical sensor) may be used to measure concentration of at least one analyte in the fluid. For example, the sensor 106a may measure the concentration of an analyte, such as glucose, in biofluid (e.g., sweat or other biofluid) extracted from the wearer-user’s body. In some embodiments, a plurality of sensors are used, each of which measures a corresponding analyte, such as glucose, lactate, vitamin C, levodopa, sodium, potassium, chloride, calcium, ammonium, alcohol, uric acid, caffeine, proteins, sweat, sweat rate, and / or other types of other analytes.

[0025] In some embodiments, the at least one sensor, such as sensor 106a may include at least two electrodes 108a and 108b to enable measurement of for example a concentration of at least a first analyte in the fluid present at the channel portion 197 of the fluidics structure 104. The at least two electrodes may comprise an anode and a cathode. Moreover, the electrodes maycomprise a reference electrode to enable a measurement using the reference electrode and another electrode. The electrodes may include the following components: enzyme, mediator, polymer, surfactant, crosslinker, stabilizer, plasticizer, antibody, aptamers, peptides, molecularly imprinted polymers (MIP), ligands, cells, protein receptor, and / or synthetic receptors. Each electrode may include a conductive current collector made of for example carbon, silver, copper, platinum, gold, and / or an alloy thereof. The enzyme may include glucose oxidase, lactate oxidase, uricase, horse radish peroxidase, cholesterol oxidase, polyphenol oxidase, tyrosinase, alcohol oxidase, glucose dehydrogenase, alcohol dehydrogenase, and / or lactate dehydrogenase. The mediator may include ferrocene, quinones, ferricyanide, tetrathiafulvalene, polyoxometalates, nicotinamide adenine dinucleotide (NADH), and / or Prussian blue. The sensor output may be measured using electrochemical techniques such as voltammetry, potentiometry, amperometry, and / or impedance, and processed with one or more algorithms to get an estimate of for example the blood glucose concentration trend or other analyte concentration. In some embodiments, the sensor is composed of Ag current collectors, carbon anode, and silver oxide cathode on the SEBS substrate. The glucose sensor can be prepared by drop casting sequentially naphthoquinone mediator, carbon nanotube, glucose oxidase solution, glutaraldehyde crosslinker and chitosan on the anode electrode. An external resistor of 1 mega-ohm is soldered between the two electrodes as the discharge load. A lactate sensor may be created by drop casting sequentially NQ, CNT, Lactate Oxidase, GA, and Chitosan on an anode electrode. An external resistor of 75 kQ was soldered between the two electrodes as the discharge load. The vitamin C and 1-dopa sensors can be prepared by drop casting sequentially TTF-TCNQ and chitosan on anode electrodes. The external discharge load used with vitamin C and 1-dopa sensor were 1 and 10 mega-ohms respectively.

[0026] In some embodiments, the osmotic pump 102 draws a fluid (e.g., biofluid, sweat, interstitial fluid, and / or the like) from the wearer’s skin via the first portion 195 of the fluidics structure 104. The fluid is drawn (via osmotic pressure from the osmotic pump 102) from the first portion 195 through the channel portion 197 (where the at least one sensor 106a is disposed) towards the third portion 199 where the osmotic pump is located. Although some of the examples refer to the fluid or biofluid as sweat, other types of fluids including interstitial fluids may be collected as well.

[0027] In some embodiments, the osmotic pump 102 is disposed on the first surface 180 of the fluidics structure 104. Alternatively, or additionally, the osmotic pump may be disposed at the first end 190 of the sensing system 100. Alternatively, or additionally, the osmotic pump may be disposed at the third portion 199 of the fluidics structure. In the example of FIG. 1, the second surface 182 of the fluidics structure is configured to be in contact with a portion of a wearer’s body, such as a finger of the wearer of the sensing system 100, to enable fluid collection.

[0028] In some embodiments, the osmotic pump 102 may comprise a gel and / or a hydrogel to passively extract or draw the biofluid (e.g., sweat and / or the like) from the wearer’s body towards the first portion 195 through the channel portion 197 (where the at least one sensor 106a is disposed) the osmotic pump 102. The osmotic pump is passive in the sense that the biofluid is collected without requiring any action on the part of the user and / or without any external power requirement (as in iontophoresis).

[0029] In some embodiments, the hydrogel may be formed by treating a solution comprising a first monomer. The first monomer may comprise acrylamide. Upon treatment, the first monomer may be polymerized to form the hydrogel. The treatment may comprise UV-curing. The treatment may comprise treatment of the solution comprising a first monomer with another solution (e.g., ethylene glycol). In some implementations, the hydrogel comprises a copolymer of polyvinyl alcohol and polyacrylamide.

[0030] The treatment of the solution comprising the first monomer may be configured to increase the osmotic pressure of the solution. The treatment of the solution comprising the first monomer may be configured to impart (unto the hydrogel) a chemical potential sufficient to establish a chemical potential gradient with respect to the chemical potential of the extracted biofluid. For example, the hydrogel may be configured to have a chemical potential between about three times and about seven times greater than the chemical potential of the fluid (e.g., sweat) extracted from the body. In some embodiments, the hydrogel comprises a chemical potential that is about five times the chemical potential of the fluid extracted from the body. By configuring the hydrogel with such a chemical potential, the swelling of the hydrogel can be controlled. By controlling the swelling of the hydrogel, it can be ensured that fluid extracted from the body is appropriately routed to the fluidics structure 104, instead of being absorbed bythe osmotic pump 102 (e.g., the hydrogel). Further, the treatment of the solution comprising a first monomer can be configured to impart unto the resultant hydrogel a desired degree of crosslinking in the polymers that are created due to the treatment of the hydrogel. By controlling the number of water-absorbing (e.g., cross-linking) polymers in the hydrogel, the swelling of the hydrogel can be reduced or controlled. The cross-linking of the polymers can be controlled by tuning the ratio of the monomers present in the solution comprising the first monomer. Further, the amount of time that the solution comprising the first monomer is treated can be selected to ensure an appropriate degree of cross-linking.

[0031] In some embodiments, the gel or hydrogel is developed using a blend of polyvinyl alcohol (PVA) and polyacrylamide (PAAm). The gel may be composed of distilled water, acrylamide, N,N'-methylenebis(acrylamide), 2-hydroxy-4'-(2-hydroxyethoxy)-2- methylpropiophenone, and PVAin the mass ratio of 0.8375:0.0293:0.0059:0.0017:0.1256. This mixture is transferred to a mold and cured in UV light for 45-60 minutes. The cured gel is transferred to a dish with pure ethylene glycol solution and soaked overnight. After that, discs of 6mm diameter are cut out using a commercial hole puncher and stored in pure ethylene glycol solutions. These circular discs (although other shapes may be implemented) may be used as in the osmotic pump.

[0032] In some embodiments, the fluidics structure 104 may be composed of paper, cellulosic materials, fibers, absorbent pad, and / or other hydrophilic materials as well as thread based material structures, such as wicks and the like. As noted above, the structure of the fluidics structure 104 may include the first portion 195 that extends to the channel portion 197. The third portion 199 may include one or more paper channels 162 separated by gaps 160.These paper channels form a so-called serpentine shape, although other shaped paper channels may be used as well. An advantage of the fluidics structure including the paper channels and gaps prolongs or controls the flow of fluid collection and delays saturation of the fluidic structure 104. The paper channels may have a surface area configured to sustain a flow (e.g., a long-term flow) of fluid through the paper channel. If the surface area of the paper channel is below a threshold surface area for example, the paper channel may be too low such that the paper channel become saturated with biofluid. In certain implementations, the paper channel becomes too saturated once it has collected about thirty microliters of fluid, for example. In some embodiments, the surface area of the paper channel is configured to allow for between about fivemicroliters of fluid and about twenty -five microliters of fluid to be collected before the paper channel becomes saturated. In certain implementations, the surface area of the paper channel is configured to allow for fluid extraction to occur for between about two-and-a-half hours and about three-and-a-half hours. In some implementations, the fluidic structure (including osmotic pump and sensors) may be disposed after saturation and a new fluidics structure (including osmotic pump and sensors) may re-use the system 100 including the fPCB 114 and the like.

[0033] The paper-based fluidic structure 104 provides a relatively high surface area (e.g., above a threshold amount of surface area). In some implementations, the surface area should be between 7 to 10 square centimeters enable the high surface area needed to allow fluid retention volume of at least 10 microliters. Moreover, the serpentine pattern or shape provides one or more of the following advantages: (a) it makes the sweat travel more distance over time; and (b) allows delaying saturation of the paper channel and prolongs sweat inflow. Furthermore, when used under high sweat rates (such as exercise), an evaporation site can also be added at one end of the channel. Evaporation of sweat will help in maintaining the capillary pressure in the channel, which eventually will allow continuous inflow of fresh sweat and prevent mixing of old and new sweat.

[0034] As noted, the at least one sensor, such as the sensor 106a, may comprise an electrochemical sensor, such that biofluid extracted from the body flows through the fluidics structure 104 and flows over the sensor 106a. In some implementations, the biofluid that flows over the sensor 106a is fresh, In other words, by coupling the fluidics structure 104 to the sensor 106a such that fluid flows over the sensor 106a, no old fluid sample remains stuck to the sensor 106 as the older fluid samples are further drawn towards the third portion 199 of the fluidic structure where the osmotic pump 102 is located.

[0035] Referring again to the sensors 106a-e and two electrodes 108a-e. In some embodiments, a first electrode, such as electrode 108e, is, as noted, a reference electrode. This reference (e.g., common or auxiliary electrode) may be configured to provide a reference, such as a reference potential relative to a second, working electrode used to measure a concentration of a first analyte in the fluid extracted from the body. For example, the second electrode may measure the concentration of an analyte (collected in the fluid extracted from the body) based on a difference in potential between the second electrode and the reference electrode. Alternatively,or additionally, the second electrode may measure the concentration based on a current established between the second electrode and reference electrode.

[0036] As noted, the sensors 106a-e may include (or be coupled to) a plurality of electrodes 108a-f. For example, a third electrode, such as electrode 108c, may be configured to measure a concentration of a second analyte in the fluid extracted from the body; a fourth electrode 108d may measure a concentration of a third analyte in the fluid extracted from the body; and so forth. Although a certain quantity of sensors and electrodes are depicted at FIG. 1, other quantities may be implemented as well (e.g., fewer or more). Alternatively, or additionally, a sensor may include a counter electrode (e.g., a cathode) and at least a first working electrode (e.g., an anode). At least the first working electrode may be developed using carbon with an oxidation-supporting mediator. The counter electrode may be developed using Ag2O. The working electrode may be coupled with the Ag2O counter electrode, which undergoes the reduction of Ag2O to Ag.

[0037] In some implementations, the sensing system 100 comprises a power source, such as at least one biofuel cell (BFCs) 110 and / or at least one battery 112. Alternatively, or additionally, the power source may include one or more capacitors, such as a supercapacitor. The sensing system may also include or printed circuit board, such as a flexible printed circuit board (fPCB) 114 (illustrated in FIG. 2).

[0038] The at least one battery 112 may comprise for example a AgCl-Zn battery, although other types of batteries may be used. Moreover, the battery may be rechargeable. Alternatively, or additionally, the battery 112 may be flexible (and / or stretchable) or capable of being shaped so that it can conform to the shape of a finger. The fPCB 114 may be bonded on the printed circuits by a rapid room-temperature solvent-welding without using any bonding layer or conductive paste, exhibiting satisfied elastic moduli. In some implementations, the biofuel cells are connected in series show an open-circuit potential (OCP) of 1.4 V and achieve their maximum power output at about 1 V. This regulated voltage ensures that the biofuel cells can consistently operate at their maximum power, enabling successful charging of the at least one battery 112. The successful charging of the at least one battery 112 may afford the at least one battery 112 a redox potential of approximately 1 V. In some implementations, by connecting two AgCl-Zn batteries in series, a combined full cell potential of around ~2 V is achieved. The at least one battery 112 may be configured to power a low-power microcontroller unit (MCU) 116 (or other type of processor and memory circuit).

[0039] In some embodiments, sweat from a user’s fingertip may be used to provide sustainable biofuel to the biofuel cells 110 for harvesting biochemical energy at rest, without relying on body movement or unpredictable external conditions, and eventually supporting energy storage in the at least one battery 112. Further, the osmotically extracted sweat supports dynamic non-invasive and continuous potentiometric sensing. The at least one battery 112 thus may be used to extend the energy storage of the system 100 by harnessing the bioenergy harvested by the biofuel cells 110, enabling continuous multiplexed sweat-sensing of key metabolic biomarkers (glucose (Glu), vitamin C (VC), and lactate (LA)) or diseases-related drugs (levodopa (L-dopa)).

[0040] The low-power MCU 116 may be configured to control the fingertip-mounted sensors, 106a-e with the generated signal being sampled via an analog-to-digital converter (ADC). This conversion process transforms the analytical data into digital outputs, and the resulting personalized diagnostics information may be wirelessly transmitted to a user interface. For example, personalized diagnostics information gleaned from the analytical data may be transmitted to a user interface via Bluetooth low energy (BLE) or other type of wired and / or wireless connection. The transmitted information may be further processed and / or directly displayed on a smartphone or laptop, leading to real-time personalized health status evaluation.

[0041] In some embodiments, the osmotic pump 102 includes a gel, such as an osmotic biofluid extraction gel. This gel may include at least one polymer or a monomer of a polymer and is treated with solvent. The polymer may include polyacrylamide, polyvinyl alcohol, alginate, chitosan, hyaluronic acid, collagen, poly(N-isopropylacrylamide), polyethylene oxide, polyacrylic acid, and gelatin. The solvent can include water, glycerol, sugar, and electrolytes. The gel can also include salt, ionic liquid, thickener, crosslinker, accelerator, initiator, and stabilizers. The gel includes salt and non-aqueous solvent to increase the osmotic pressure with respect to the skin, which facilitates sweat extraction. All solvents used to treat hydrogel are benign to the human skin upon contact. The gel can be treated with either low volatile benign solvent (such as glycerol) or be hosted inside a chamber to prevent it from drying during longterm on-skin testing.

[0042] FIG. 2 illustrates an exploded view of the sensing system 100 in accordance with some embodiments described herein, while FIG. 3 illustrates the sensing system 100 disposed on afingertip of a user. FIG. 4 illustrates a flattened, layout version of the sensing system 100, in accordance with some embodiments described herein.

[0043] FIG. 5 depicts an example of a sensing system 500, in accordance with some embodiments. The sensing system 500 is similar in some respects to sensing system 100 but is configured as a sweat-based continuous glucose monitor. Referring to FIG. 5, the sensing system 500 includes a fluidic structure 104 including a sensor 506 including two electrodes 108a-b disposed at the channel portion of the fluidic structure, The osmotic pump 102 draws the finger’s 500 sweat from the first portion 195 of the fluidics structure 104 through the channel portion 197 (where the sensor 506 and electrodes 108a-b are located) and into the third portion 199. The electrodes may carry the measurements to a printer circuit board (e.g., fPCB 114) or other type of memory and processor based device. And, the sensing system 500 power may be provided by one or more batteries, one or more biocell(s), and / or other types of power sources. The osmotic effect is deployed on skin with a high solute-containing hydrogel at the osmotic pomp 102, while the sweat transport is achieved using the fluidic structure 102 (e.g., a paper microfluidic channel as noted above with respect to 162). The use of osmosis may facilitate greater sweat collection compared to natural perspiration alone, which can be executed at different body locations by tuning the hydrogel composition and osmolyte strength. Although FIG 5 depicts the sensing system at the finger, the sensing system 500 may be placed on other surfaces of the body.

[0044] FIG. 6 depicts an example implantation of the sensing system 500. Referring to FIG. 6, the components of the sensing system 500 are encased using stretchable styrene-ethylene- butylene-styrene (SEBS) thermoplastic elastomeric substrates 510a-b, although other types of substrates may be used as well. The substrates 510a-b may prevent the drying of the hydrogel used by the osmotic pump 102 and paper of the fluidic structure 104, while allowing conformal adherence of the sensing system onto the fingertip (or other body part, such as a forearm) where there is a high sweat gland density. The paper channel of the fluidics structure 104 stays sandwiched between the electrode and top SEBS 510a cover. The first portion 195 of the fluidics structure may be sized and shaped as a rectangular section with a relatively large surface area (e.g., 7.2 cm2) to facilitate the prolonged sweat flow via capillary action and prevent the intermixing with old sweat, although other sizes and shapes may be used as well.

[0045] The biofluid (e.g., sweat glucose) collected by the fluidic structure 104 gets detected by the sensor 506. The sensor may be a self-powered, mediator-based and oxygen-independent enzymatic glucose biosensor as shown at FIG. 7, although other type of sensors may be used as well. In the example of FIG. 7, the sensor includes a two-electrode system and relies on its intrinsic potential difference to operate. For example, the anode uses a porous carbon ink along with 1,4 napthaquinone (NQ) mediated oxidation of glucose by the glucose oxidase enzyme (GOx), with open circuit potential (OCP) of about -0.15 V. The cathode is developed using Ag2O (OCP -+0.27 V vs Ag / AgCl) which reduces to Ag. An external load of IMG drives the current flow between the two electrodes, which is dominated by the concentration-limited electrocatalytic reaction on the GOx electrode.

[0046] In some embodiments, there may be provided a method. The method may include applying a system including an osmotic pump to a skin surface and extracting by the system biofluid from the skin surface, wherein the system comprises the osmotic pump; a fluidics structure coupled to the osmotic pump, the fluidics structure including a first surface and a second surface distal to the first surface, the fluidics structure having a first end and a second end distal to the first end, the fluidics structure comprising a first portion that extends to a channel portion which extends to a third portion; at least one sensor configured to measure a concentration of at least a first analyte in a biofluid collected using the system; wherein the osmotic pump is disposed on the first surface of the fluidics structure and at the first end of the fluidics structure and at the first portion of the fluidics structure; wherein the osmotic pump is configured to draw the biofluid from a skin surface towards the osmotic pump via the first portion of the fluidics structure through the channel portion where the at least one sensor is disposed; and wherein the second surface of the fluidics structure is configured to be in contact with the skin surface of a wearer of the system to enable the biofluid collection.

[0047] In view of the above-described implementations of subject matter this application discloses the following list of examples, wherein one feature of an example in isolation or more than one feature of said example taken in combination and, optionally, in combination with one or more features of one or more further examples are further examples also falling within the disclosure of this application:Example 1 : A system comprising: an osmotic pump; a fluidics structure coupled to the osmotic pump, the fluidics structure including a first surface and a second surface distal to the first surface, the fluidics structure having a first end and a second end distal to the first end, the fluidics structure comprising a first portion that extends to a channel portion which extends to a third portion; at least one sensor configured to measure a concentration of at least a first analyte in a biofluid collected using the system; wherein the osmotic pump is disposed on the first surface of the fluidics structure and at the first end of the fluidics structure and at the first portion of the fluidics structure; wherein the osmotic pump is configured to draw the biofluid from a skin surface towards the osmotic pump via the first portion of the fluidics structure through the channel portion where the at least one sensor is disposed; and wherein the second surface of the fluidics structure is configured to be in contact with the skin surface of a wearer of the system to enable the biofluid collection.Example 2. The system of Example 1, further comprising: a source of power for the system, wherein the source of power includes at least one battery, at least one biofuel cell configured to harvest biofluid from the wearer to provide bioenergy for the system, and / or at least one supercapacitor.Example 3. The system of any of Examples 1-2, wherein the skin surface is located at a finger and / or a forearm.Example 4. The system of any of Examples 1-3, wherein the biofluid comprises sweat and / or an interstitial fluid collected by the fluidics structure from the wearer of the system.Example 5. The system of any of Examples 1-4, wherein at least one sensor comprises a plurality of sensors, each of the plurality of sensors configured to measure a corresponding analyte.Example 6. The system of any of Examples 1-5, wherein the at least one sensor measures at least the first analyte, wherein the first analyte comprises glucose, lactate, vitamin C, levodopa, sodium, potassium, chloride, calcium, ammonium, alcohol, uric acid, caffeine, proteins, sweat, and / or a sweat rate.Example 7. The system of any of Examples 1-6, wherein the at least one sensor includes at least two electrodes, wherein the at least two electrodes include an anode and a cathode.Example 8. The system of any of Examples 1-7, wherein the at least two electrodes includes a reference electrode.Example 9. The system of any of Examples 1-8, wherein the at least two electrodes include a conductive current collector.Example 10. The system of any of Examples 1-9, wherein the at least two electrodes include one or more of enzyme, mediator, polymer, surfactant, crosslinker, stabilizer, plasticizer, antibody, aptamers, peptides, molecularly imprinted polymers (MIP), ligands, cells, protein receptor, and / or synthetic receptors.Example 11. The system of any of Examples 1-10, wherein the enzyme includes glucose oxidase, lactate oxidase, uricase, horse radish peroxidase, cholesterol oxidase, polyphenol oxidase, tyrosinase, alcohol oxidase, glucose dehydrogenase, alcohol dehydrogenase, and / or lactate dehydrogenase.Example 12. The system of any of Examples 1-11, wherein the mediator includes ferrocene, quinones, ferricyanide, tetrathiafulvalene, polyoxometalates, nicotinamide adenine dinucleotide (NADH), and / or Prussian blue.Example 13. The system of any of Examples 1-12, wherein the at least one sensor measures at least the first analyte based on voltammetry, potentiometry, amperometry, and / or impedance, and / or wherein the measurements are processed to determine an estimate of a blood glucose concentration trend or other trend of the first analyte.Example 14. The system of any of Examples 1-13, wherein the osmotic pump comprises a gel including at least one polymer or at least one monomer, wherein the gel is treated with a solvent.Example 15. The system of any of Examples 1-14, wherein the polymer is composed of polyacrylamide, polyvinyl alcohol, alginate, chitosan, hyaluronic acid, collagen, poly(N-isopropylacrylamide), polyethylene oxide, polyacrylic acid, and / or gelatin.Example 16. The system of any of Examples 1-15, wherein the solvent is composed of water, glycerol, sugar, and / or electrolytes.Example 17. The system of any of Examples 1-16, wherein the fluidics structure comprises a paper based material.Example 18. The system of any of Examples 1-17, wherein the fluidics structure is shaped as a serpentine to provide a channel for the biofluid.

[0048] One or more aspects or features of the subject matter described herein can be realized in digital electronic circuitry, integrated circuitry, specially designed ASICs, field programmable gate arrays (FPGAs) computer hardware, firmware, software, and / or combinations thereof These various aspects or features can include implementation in one or more computer programs that are executable and / or interpretable on a programmable system including at least one programmable processor, which can be special or general purpose, coupled to receive data andinstructions from, and to transmit data and instructions to, a storage system, at least one input device, and at least one output device. The programmable system or computing system may include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other. These computer programs, which can also be referred to as programs, software, software applications, applications, components, or code, include machine instructions for a programmable processor, and can be implemented in a high-level procedural and / or object- oriented programming language, and / or in assembly / machine language. As used herein, the term “machine-readable medium” refers to any computer program product, apparatus and / or device, such as for example magnetic discs, optical disks, memory, and Programmable Logic Devices (PLDs), used to provide machine instructions and / or data to a programmable processor, including a machine-readable medium that receives machine instructions as a machine-readable signal. The term “machine-readable signal” refers to any signal used to provide machine instructions and / or data to a programmable processor. The machine-readable medium can store such machine instructions non-transitorily, such as for example as would a non-transient solid- state memory or a magnetic hard drive or any equivalent storage medium. The machine-readable medium can alternatively or additionally store such machine instructions in a transient manner, such as for example, as would a processor cache or other random access memory associated with one or more physical processor cores.

[0049] In the descriptions above and in the claims, phrases such as “at least one of’ or “one or more of’ may occur followed by a conjunctive list of elements or features. The term “and / or” may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For example, the phrases “at least one of A and B;” “one or more of A and B;” and “A and / or B” are each intended to mean “A alone, B alone, or A and B together.” A similar interpretation is also intended for lists including three or more items. For example, the phrases “at least one of A, B, and C;” “one or more of A, B, and C;” and “A, B, and / or C” are each intended to mean “A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together.” Use of the term “basedon,” above and in the claims is intended to mean, “based at least in part on,” such that an unrecited feature or element is also permissible.

[0050] The subject matter described herein can be embodied in systems, apparatus, methods, and / or articles depending on the desired configuration. The implementations set forth in the foregoing description do not represent all implementations consistent with the subject matter described herein. Instead, they are merely some examples consistent with aspects related to the described subject matter. Although a few variations have been described in detail above, other modifications or additions are possible. In particular, further features and / or variations can be provided in addition to those set forth herein. For example, the implementations described above can be directed to various combinations and subcombinations of the disclosed features and / or combinations and subcombinations of several further features disclosed above. In addition, the logic flows depicted in the accompanying figures and / or described herein do not necessarily require the particular order shown, or sequential order, to achieve desirable results. Other implementations may be within the scope of the following claims.

Claims

What is claimed:

1. A system compri sing : an osmotic pump; a fluidics structure coupled to the osmotic pump, the fluidics structure including a first surface and a second surface distal to the first surface, the fluidics structure having a first end and a second end distal to the first end, the fluidics structure comprising a first portion that extends to a channel portion which extends to a third portion; at least one sensor configured to measure a concentration of at least a first analyte in a biofluid collected using the system; wherein the osmotic pump is disposed on the first surface of the fluidics structure and at the first end of the fluidics structure and at the first portion of the fluidics structure; wherein the osmotic pump is configured to draw the biofluid from a skin surface towards the osmotic pump via the first portion of the fluidics structure through the channel portion where the at least one sensor is disposed; and wherein the second surface of the fluidics structure is configured to be in contact with the skin surface of a wearer of the system to enable the biofluid collection.

2. The system of claim 1, further comprising: a source of power for the system, wherein the source of power includes at least one battery, at least one biofuel cell configured to harvest biofluid from the wearer to provide bioenergy for the system, and / or at least one supercapacitor.

3. The system of claim 1, wherein the skin surface is located at a finger and / or a forearm.

4. The system of claim 1, wherein the biofluid comprises sweat and / or an interstitial fluid collected by the fluidics structure from the wearer of the system.

5. The system of claim 1, wherein at least one sensor comprises a plurality of sensors, each of the plurality of sensors configured to measure a corresponding analyte.

6. The system of claim 1, wherein the at least one sensor measures at least the first analyte, wherein the first analyte comprises glucose, lactate, vitamin C, levodopa, sodium, potassium, chloride, calcium, ammonium, alcohol, uric acid, caffeine, proteins, sweat, and / or a sweat rate.

7. The system of claim 1, wherein the at least one sensor includes at least two electrodes, wherein the at least two electrodes include an anode and a cathode.

8. The system of claim 7, wherein the at least two electrodes includes a reference electrode.

9. The system of claim 7, wherein the at least two electrodes include a conductive current collector.

10. The system of claim 7, wherein the at least two electrodes include one or more of enzyme, mediator, polymer, surfactant, crosslinker, stabilizer, plasticizer, antibody, aptamers, peptides, molecularly imprinted polymers (MIP), ligands, cells, protein receptor, and / or synthetic receptors.

11. The system of claim 10, wherein the enzyme includes glucose oxidase, lactate oxidase, uricase, horse radish peroxidase, cholesterol oxidase, polyphenol oxidase, tyrosinase, alcohol oxidase, glucose dehydrogenase, alcohol dehydrogenase, and / or lactate dehydrogenase.

12. The system of claim 10, wherein the mediator includes ferrocene, quinones, ferricyanide, tetrathiafulvalene, polyoxometalates, nicotinamide adenine dinucleotide (NADH), and / or Prussian blue.

13. The system of claim 1, wherein the at least one sensor measures at least the first analyte based on voltammetry, potentiometry, amperometry, and / or impedance, and / or wherein the measurements are processed to determine an estimate of a blood glucose concentration trend or other trend of the first analyte.

14. The system of claim 1, wherein the osmotic pump comprises a gel including at least one polymer or at least one monomer, wherein the gel is treated with a solvent.

15. The system of claim 14, wherein the polymer is composed of polyacrylamide, polyvinyl alcohol, alginate, chitosan, hyaluronic acid, collagen, poly(N- isopropylacrylamide), polyethylene oxide, polyacrylic acid, and / or gelatin.

16. The system of claim 14, wherein the solvent is composed of water, glycerol, sugar, and / or electrolytes.

17. The system of claim 1, wherein the fluidics structure comprises a paper based material.

18. The system of claim 1, wherein the fluidics structure is shaped as a serpentine to provide a channel for the biofluid.

19. A method compri sing : applying a system including an osmotic pump to a skin surface; and extracting, by the system, biofluid from the skin surface, wherein the system comprises any one of claims 1-19.

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