Integrated device for sampling, storage, and analysis of human milk

Abstract

Disclosed herein are devices, kits and methods relating to the collection and analysis of a biofluid from a mammary gland of a subject. Exemplary embodiments can include a pad with fluidic channels to collect the biofluid and one or more sensors to analyze the biofluid. The pad may comprise a plurality of layers, and may be an integral part of the device or an existing pad to which the device is coupled. The pad may also comprise one or more cutouts that extend partially or completely through the one or more layers of the device to allow the pad to conform to the shape of the mammary gland.

Description

INTEGRATED DEVICE FOR SAMPLING, STORAGE, AND ANALYSIS OF HUMAN MILKTECHNICAL FIELD

[0001] The present invention generally relates to devices configured to collect and / or evaluate breast milk, and diagnose and monitor potential disorders. Also disclosed are kits comprising such devices and methods of making the same.BACKGROUND OF THE INVENTION

[0002] Analysis of human milk is essential for advancing both infant and maternal health. While the link between nutrition and health has long been recognized and modern tools allow detailed monitoring of dietary intake, similar capabilities are lacking for breast milk — Ihc primary source of neonatal nutrition. Despite its critical role in supporting infant growth, immunity, and development, there are currently limited tools for assessing the detailed composition and nutritional quality of human milk. Breast milk is an ideal nutritional source for infants, and plays an important role in multiple aspects of overall health of infant including physical, cognitive, and behavioral development [1,2], Breast milk has also demonstrated a prophylactic effect against many acute and chronic conditions such as sudden infant death syndrome (SIDS), asthma, and obesity [3], Breast milk composition, however, can undergo dramatic changes based on the lactating individual’s nutritional status as well as the presence of metabolic disorders. This change in composition has the potential to significantly impact the child’s growth and development [4, 5], Frequent monitoring of the nutritive factors in breast milk is critical for instituting early intervention strategies such as a change in diet of the nursing parent, supplementation, or medical management in case of deficiencies in milk. Implementing these strategies is most critical for infants vulnerable to growth complications such as those bom premature or with preexisting conditions.

[0003] Beyond its role in infant nutrition, frequent analysis of milk composition is also vital for monitoring maternal and mammary gland health. Mastitis, commonly occurring during lactation, often results from milk stasis within the mammary ducts. The World Health Organization defines four stages: milk stasis, non-infectious mastitis, infectious mastitis, and abscess formation [6], Milk stasis, caused by inadequate milk expression, leads to ductal blockage and swelling, progressing to non-infectious mastitis. Inflammation in breast tissue increases susceptibility to infection, leading to infectious mastitis that typically requires systemic antibiotics and complete milk 14905-3262-5274, v. 1expression to prevent abscess formation. Once an abscess develops, surgical drainage and antibiotic therapy are necessary [6,7], Studies indicate that most mastitis cases require antibiotic treatment, and a notable portion can progress to abscesses if not promptly managed [8, 9], Delayed treatment significantly increases the likelihood of coinplicalions, underscoring the importance of early diagnosis. Although preclinical dcleclion through milk biomarkers is feasible

[0010] , routine screening remains limited due to the lack of accessible, high-frequency diagnostic tools.

[0004] Another key aspect of breastfeeding is the transfer of medications from the mother to the infant through breast milk. Drugs taken by the mother can be secreted into milk and ingested by the infant; however, breastfeeding should only be discontinued if a specific medication poses a greater risk to the infant than the benefits of breastfeeding

[0011] , Developing rapid tools to evaluate drug concentrations in milk is therefore essential for managing breastfeeding during maternal medication use. Drug secretion into milk involves multiple physiological stages, including ingestion, absorption, circulation, and secretion. For instance, acetaminophen is metabolized in the liver before entering the bloodstream and reaching the mammary glands, where it passes into milk via active transport, passive diffusion, or apocrine secretion. The milk-to-plasma ratio, which compares drug concentrations in milk and plasma, determines the level of infant exposure [11, 12], Factors affecting this ratio include protein binding capacity, lipid solubility, molecular weight, drug pKa, and volume of distribution

[0011] ,

[0005] In addition to factors related to the chemical structure of the drug (pKa, solubility, molecular weight), parameters such as age, genetic factors, pathophysiological conditions (i.e., liver disease), body composition, blood flow to tissues, and protein binding capacity all will affect the Vd, and consequently the milk to plasma rat io and the amount of drug in breast milk

[0011] , The heterogeneity of drug secretion in milk is evident from different milk to plasma ratios reported for acetaminophen, all measured from a limited number of study subjects

[0013] , This necessitates frequent and personalized monitoring of drug concentrations in breast milk. Currently, monitoring of medication concentration in breast milk has not been adopted clinically, likely due to a lack of tools able to provide affordable analysis in milk at the point of care.

[0006] Tools for at-home or on-body biochemical analysis are limited. Several products and services for biochemical analysis of breast milk have recently emerged to support breastfeeding management. In 2018, the U.S. Food and Drug Administration (FDA) approved the Miris Human Milk Analyzer (US 7,132,660 B2) for hospital use to quantify breast milk nutrients

[0014] , This infrared-based bench-top instrument is costly, requires trained personnel, and is thus confined to hospital laboratories and milk banks

[0015] , Commercial mail-in services offer another option for nutrient analysis, where users collect milk samples using provided kits and ship them to 24905-3262-5274, v. 1company laboratories. However, these services, priced between $49-$349 [16, 17], introduce logistical challenges and delays in obtaining results. Currently, the only low-cost at-home breast milk test available is the alcohol test strip, designed to detect alcohol, which can negatively affect an infant’s development, growth, and circadian rhythm [18-21], The user applies milk to the strip and observes a color change to determine alcohol presence. However, this strip is limited to alcohol detection only and lacks integration features such as on-body sampling, fluidic processing, or multiplexed biochemical analysis.

[0007] The state-of-the-art tools pose numerous challenges for obtaining useful information through the analysis of breast milk. The expensive mail-in-kits only allow limited number of testings (depending on what the parents can afford) and provide the results with several weeks of delay. The composition of breast milk changes over time to accommodate the needs of a growing child, and is also dependent on the mother’s, therefore frequent analysis is needed to obtain actionable and relevant information on milk content. Another challenge is praclicalily : new parents are often very busy and may lack the time to research testing facilities and collect samples for mail-in services. For breast milk collection and analysis to be practical for busy families, it must be quick, affordable, discreet, and easy to use.

[0008] Lactating individuals face unique health concerns such as nutritional deficiencies, mastitis development, and drug transference through their milk. Therefor it seems only natural to take advantage of a freely-available, non-invasive biofluid to help these individuals monitor the health of themselves and their child. The introduction of accessible, home-based wearable devices for breast milk analysis has the potential to revolutionize the breastfeeding experience. Such devices could empower families with immediate data, offering a safe and well-monitored breastfeeding journey that prioritizes infant nutrition and maternal health.

[0009] What is needed is an integrated system that can easily sample milk, process it, and enable the milk transport to a zone for further analysis. Most discussed prior work relied on large volumes of breast milk that should be collected via pumping or other means. Not all women use pumps to extract and store milk in containers and some only rely on natural feeding, making it difficult to obtain large milk volumes to use the mail-in milk analysis services. This invention describes a multi-layered device, which is an integrated pad in certain embodiments, that can be worn against the breast to sample the small volumes of milk that can be released due to involuntary milk leakage or through hand expression. Involuntary milk leakage, also known as the let-down reflex or milk ejection reflex, is a natural response in nursing women where breast milk is released from the mammary papilla without conscious control. This occurs when the body signals the milk-producing glands to release milk and can be triggered by various factors, including common triggers such as 34905-3262-5274, v. 1hearing a baby cry, or thinking about the baby, or experiencing physical stimulation like breastfeeding or mammary papilla contact

[0022] or hormonal changes (particularly the release of oxytocin). Some women may experience milk leakage at unexpected rimes, such as between feedings or during strong emotional reactions

[0022] , To manage the in-voluntary milk leakage, women often use breast pads (known as lactation pads or nursing bra pads) to absorb the milk and keep the cloth and skin dry. Typically worn for several hours or all day, these pads have a high milk absorption capacity and are discarded with the collected milk at day’s end, without getting any health information or information about the composition of the milk.

[0010] FIG. 1 shows the components of a lactation pad (labeled as 10) that is worn against the breast (labeled as 11). This pad comprises of a water-permeable first layer 13, an absorbing material 14, a water-impermeable layer 15, and an adhesive 16 that is exposed by removing a protecting barrier 17, to secure to the lactation pad to the bra. This lactation pad is the prior art for pads that interface with breast tissue. The absorbing material 14 absorbs the milk and keeps the cloth and skin dry. The disclosed device introduces, for the first time, the integration of fluid storage and sensing capabilities into a lactation pad, thereby transforming it into a “smart lactation pad” with enhanced functionalities. These advancements enable the analysis of biofluid properties and provide insights into the health of the wearer. The invention birther includes embodiments of wearable pads that can couple with standard lactation pads, imparting fluid sensing and / or storage flmctionalities. This enhancement allows for real-time and / or bequent milk analysis or the collection and storage of milk within specialized fluidic layers, facilitating subsequent laboratory analysis and centralized evaluation. The pad, in various embodiments, is designed to be disposable after use, ensuring practicality and convenience.

[0011] A wearable device as such described in this invention can take advantage of the routine process of lactating women wearing a pad to sample the leaked milk during the day for immediate analysis or for storage for analysis at a later time. Wearable technologies such as smart watches, wound dressings, bracelets, armbands, and glasses have become increasingly integrated into daily life. These devices have tansformed healthcare by alleviating hospital workloads and enabling continuous, reliable monitoring for diagnosis and therapy management. Many wearables now incorporate sampling and sensing systems capable of detecting chemical and biological markers in biofluids such as saliva, urine, and sweat, and can be worn on various body parts, including the eye, head, wrist, and fingers, to support health monitoring and medical testing. Despite these advances, women’s health has been largely overlooked, and no wearable devices currently exist for interfacing with the breast to sample biofluids from the mammary glands.44905-3262-5274, v. 1

[0012] Wearable sensors for point-of-care and at-home testing of milk will be an ideal solution for frequent monitoring of milk composition. A wearable patch for on-body milk capture and storage should be flexible and comfortable to wear against skin, be able to conform to the breast shape, and have fluidic inlets close to the mammary glands for milk capture. Moreover, the patch should contain a water-impermeable backing to avoid milk leakage to the user’s cloth.

[0013] This disclosure presents wearable device and point-of-care devices designed for on-breast application to sample breast milk and perform chemical analysis. In certain embodiments, the device incorporates sensors and microfluidic channels into a lactation pad. Lactation pads are typically worn over the breasts to absorb naturally occurring milk leakage, preventing clothing from becoming wet. Currently, the milk collected in these pads is discarded without analysis. By integrating microfluidic channels, a portion of the leaked milk is directed to a sensing zone where sensors assess a composition of fluid secreted from mammary glands. This pioneering device represents the first wearable technology for both on-body sampling and biochemical analysis of breast milk, establishing a platform for detecting various biomarkers. Importantly, this design retains the primary fimction of the lactation pad, ensuring that it does not add any additional burden to the user.

[0014] Research and prior inventions related to devices that mount over the breasts for collection of milk include wearable breast pumps (US11235093B1, US11097039B2, US10639407B2, US12115294B2, US10046097B2, US20200155738A1, ES2949271T3, USD936823S1, USD969305S1). Such pumps usually use vacuum to actively extract the milk and cannot be described as a pad. Other inventions include specialized nursing bra garments (US20200404984A1, US11304457B2) that enable easy access to the breasts during breastfeeding. None of the prior art have attempted to develop a pad shaped device for passive collection of leaked milk and for sensing of the fluid composition either in a point-of-care or wearable setting.SUMMARY OF THE INVENTION

[0015] Embodiments of the present disclosure include devices, kits and methods related to the collection and analysis of a biofluid from a mammary gland of a subject.

[0016] Exemplary embodiments of the present disclosure include a device comprising a pad comprising a first side, a second side and one or more fluidic channels wherein: the first side of the pad is configured to be worn against a mammary gland of a user; and the one or more fluidic channels are configured to collect a biofluid from the mammary gland, and / or mammary ducts, and / or mammary papilla of the user. In certain embodiments the device is configured to analyze54905-3262-5274, v. 1a composition of the biofluid. In particular embodiments the biofluid is human milk. In some embodiments the one or more fluidic channels extend from the first side of the pad to the second side of the pad. In sped He embodiments the second side of the pad comprises a hydrophobic and / or water impermeable and / or water resistant material. In certain embodiments the second side of the pad contains an adhesive. In particular embodiments the device contains at least one fluidic channel layer, one water-permeable layer, one water-impermeable layer, and an oplional fluidic processing layer. In some embodiments the device couples with a lactation pad and / or an absorbing material.

[0017] In specific embodiments the fluid processing layer any of filtration, separation, mixing one or more reagents, transferring to one or more sensors, or any combination thereof. In certain embodiments the one or more fluidic channels are hydrophilic. In particular embodiments the one or more fluidic channels comprise a hydrophobic edge at the first side of the pad. In some embodiments the absorbent material comprises natural materials or polymeric materials. In specific embodiments the natural materials are selected from cotton, linen, silk, wool, hemp, ramie, bamboo, cellulose -based materials, or any combination thereof. In certain embodiments the polymeric materials are selected from poly- acrylate, sodium polyacrylate, a super-absorbing polymer, polyamide, polyethylene, polypropylene, polyester, polyoxymethylene, polyvinyl alcohol, polycarbonates, silicones, fluoropolymers, polyketones, polyacrylic, polystyrenes, poly- lactic acid, poly(lactic-co-glycolic) acid, polyurethane, polyetheretherketone (PEEK), polyimide, polyethylene terephthalate (PET), polyvinyl chloride (PVC), chitosan, thermoplastic elastomers (TPE), polycaprolactone (PCL), polyphenylene sulfide (PPS), acrylic (PMMA), and nylon. In particular embodiments the device further comprises at least one wicking element and / or fluid processing layer, wherein the at least one wicking element and / or one fluid processing layer is in fluid communication with the one or more fluidic channels.

[0018] In some embodiments the at least one wicking element and / or fluid processing layer comprises a paper, glass fiber, nitrocellulose, textile, or any combination thereof. In specific embodiments the at least one wicking element exhibits a capillary wicking. In certain embodiments the at least one wicking element is configured to allow for continuous flow of the biofluid. In particular embodiments the at least one wicking element comprises a terminal end that allow for continuous flow of the biofluid.

[0019] In particular embodiments the at least one wicking element comprises a terminal end that is connected to an absorbing material. In some embodiments the at least one wicking element comprises one or more agents. In specific embodiments the one or more agents comprise a surfactant, a stabilizer, a pH buffer, a pharmacologically active agent, a reagent configured to 64905-3262-5274, v. 1assist in a sensing reaction and / or biomarker stabilization, fluid transport, or any combination thereof. In certain embodiments the at least one wicking element is optionally independently removable from the device. Certain embodiments further comprise a sensory portion comprising one or more sensors, wherein the sensory portion is in fluid communication with the one or more fluidic channels. In particular embodiments the one or more sensors comprise a yarn or fiber. In some embodiments the sensory portion is in fluid communication with the at least one wicking element. In specific embodiments the one or more sensors comprise an optical sensor, a lateral flow assay, a colorimetric assay, an electrochemical sensor, a capacitive sensor, a thermal sensor, a magnetic sensor, a surface-enhanced Raman scattering (SERS)-based sensor, or sensor based on electrochemiluminescence (also known as electrogenerated chemiluminescenceor ECL), or any combination thereof.

[0020] In certain embodiments the electrochemical sensor comprises one or more electrodes, wherein at least one electrode is a reference electrode and at least one electrode is a working electrode. In particular embodiments the electrochemical sensor comprises of more electrodes, where at least one electrode is a counter or auxiliary electrode. In particular embodiments the electrochemical sensor contains more than one working electrode. In some embodiments the one or more sensors comprise a conductive material and / or a semiconductive material. In specific embodiments at least one sensor is flexible and / or stretchable. In certain embodiments at least a portion of a surface of one or more electrodes is modified with a reagent. In certain embodiments one or more reagents comprise one or more of an organic molecule, an antibody, nucleic acid, aptamer, enzyme, nanobody, peptide, a protein, a hydrogel, a polymer, a nanoparticle, a metal organic framework (MOF), covalent-organic frame-works (COF), a biological and / or an organic biorecognition element, an ion-sensing membrane, or a plurality of nano and microparticles or any combination thereof.

[0021] In particular embodiments the one or more sensors are configured to detect a level of an ion, an organic molecule, a protein, a metabolite, a drug, an antibody, a hormone, and a nucleic acid in the biofluid. In some embodiments the device contains a processing unit. In specific embodiments the processing unit is an electronic element. In specific embodiments the electronic element comprises an electronic processor. In certain embodiments at least a portion of the device is disposable. In certain embodiments at least a portion of the device is reusable. In particular embodiments the device is electronically connected to a processing unit configured to evaluate and / or indicate a characteristic of at least one property of the biofluid. In some the processing unit comprises a plurality of receiver channels, each processing channel comprising a sensor. In specific embodiments the processing unit is directly coupled with the device, or it is a 74905-3262-5274, v. 1separate unit.

[0022] In certain embodiments the processing unit is in a wireless or wired communication with the device. In particular embodiments the processing unit is a detector, a potentiostat, a potentiometer, or a combi nation thereof. In some embodiments the processing unit may contain a flexible circuit. In specific embodiments the flexiblecircuit is removable. In certain embodiments the sensors may connect to each other and / or to the circuit via snap-on-buttons. In particular embodiments the device is electrically connected to the processing unit via a yarn. In some embodiments the device is in wireless communication with a handheld device configured to provide a data analysis to a user. In certain embodiments the handheld device is a phone, a ring, a tablet, a computer, a watch, or any combination thereof.

[0023] In particular embodiments the device is insertable and / or attachable to an article of clothing. In some embodiments the device is reversibly insertable and / or attachable to an article of clothing. In specific embodiments the device is an article of clothing. In certain embodiments the article of clothing is a bra. In particular embodiments the device further comprises a receptacle in fluid communication with the one or more fluidic channels. In some embodiments the receptacle comprises an absorbent material. In specific embodiments the receptacle is a detachable receptacle. In certain embodiments the detachable receptacle comprises a plurality of colorimetric assays, each configured to detect a distinct biomarker. In particular embodiments the detachable receptacle can be removed from the body and be placed in a separate device. In some embodiments the separate device processes the fluid via any of heating, sonication, rotation, centrifugation, vibration, dispensing reagents, applying energy in form of sound, ultrasound, light, radiation, magnetic, voltage, and / or measures a property of the fluid via microscopy and imaging, and / or per-forming analysis, data storage, and / or data visualization. In specific embodiments the biofluid is transferred to the receptacle and undergoes a processing step.

[0024] In certain embodiments the receptacle further comprises an electronic element. In particular embodiments the receptacle comprises one or more sensors for at least one biomarker. In some embodiments at least one wicking element is disposed within the receptacle, and wherein the at least one wicking element is optionally independently removable from the device. In specific embodiments the receptacle comprises a sensory portion comprising one or more sensors, wherein the sensory portion is in fluid communication with the one or more fluidic channels. In certain embodiments the pad is configured to couple to a lactation pad. In particular embodiments the sensors are configured to perform analysis based on either a distance traveled by the biofluid within the one or more fluidic channels or a length of color developed in the one or more fluidic channels, and wherein the device comprises corresponding markings to facilitate 84905-3262-5274, v. 1quantitative assessment.

[0025] In certain embodiments the one or more fluidic channels comprise markings configured for the quantification of fluid flow or reaction results, and wherein the markings are configured to enable measurement based on the distance traveled by the fluid or the length of a color change formed within the channel, thereby facilitating quantitative and / or semi-quantitative assessments. In particular embodiments the one or more fluidic channels comprise at least one valve configured to regulate, direct, or restrict the flow of the biofluid within the channels. In some embodiments the at least one valve is a mechanical valve, pneumatic valve, thermally-actuated valve, electrochemical valve, or elastomeric valve. In specific embodiments the device can be in fluidic communication with a lactation pad through an open microfluidic channel and wherein the lactation pad can facilitate fluidic transfer in the device.

[0026] In certain embodiments a portion of the device contains an Radio Frequency Identification (RFID) component configured for one or more of the following fiinctions: tracking the usage of the device, identifying the device, monitoring environmental conditions, storing data related to fluid analysis, facilitating wireless communication of data to external devices, enabling authentication and security features, or assisting in inventory management. In certain embodiments, the device comprises one or more inductive coils configured to enable wireless power transfer for device operation, data acquisition, or signal transduction. The inductive coils may be arranged to facilitate near-field or resonant inductive coupling, thereby providing stable, contactless energy delivery to internal electronic components such as sensors, analyzers, data storage modules, or communication circuits. In some embodiments, the inductive system may fiirther serve as a dualfunction element for both power transfer and data communication through modulation of the inductive link. In certain embodiments the device fiirther comprises an integral analyzer.

[0027] Particular embodiments include a method of manufacturing the device of any one of the claims, wherein the pad is manufactured by altering a lactation pad. Specific embodiments include a method of using the device of any one of claims, comprising the steps of placing the device on the body of a subject, wherein the sensors measure a concentration of a drug or drug metabolite in the biofluid over time. Certain embodiments further comprise analyzing collected data to monitor pharmacokinetics of the drug, including absorption, distribution, metabolism, and / or excretion. In particular embodiments the sensors monitor the concentration of the drug in the biofluid to determine whether the concentration is within a therapeutic range, and adjusting the drug dosage based on the concentration to maintain or modify therapeutic efficacy. Certain embodiments include a method of using the device of any one of claims, comprising the steps of measuring a concentration of a drug or drug metabolite in breast milk and simultaneously or 94905-3262-5274, v. 1sequentially measuring the concentration in plasma, to calculate the milk-to-plasma ratio of the drug and assess drug transfer to breast milk for pharmacological and / or safety evaluations and / or health evaluations.

[0028] Particular embodiments include a method of using the device of any one of claims for diagnosis and monitoring of mastitis. Some embodiments include a kit comprising a plurality of the devices of any one of claims. In specific embodiments the kit further comprises one or more active reagents provided separately from the device or within the device. Certain embodiments further comprise a container con figured to receive the device comprising a collected biofluid of a user. In particular embodiments the container is configured to be delivered for analysis. In some embodiments the container is a biohazard container. In specific embodiments the kit comprises a user manual. In specific embodiments a portion of the kit comprises an Radio Frequency Identification (RFID) component configured for one or more of the following functions: tracking the usage of the device, identifying the device, monitoring environmental conditions, storing data related to fluid analysis, lacili tali ng wireless communication of data to external devices, enabling authentication and security features, or assisting in inventory management. In certain embodiments the kit is configured to detect mastitis, wherein the one or more sensors of the pad are configured to detect the level of sodium, potassium, pH, and chloride, and / or a ratio of sodium to potassium in the biofluid.

[0029] Particular embodiments include a kit comprising a device of any one of the claims and an article of clothing. In some embodiments the article of clothing contains the device. In specific embodiments the article of clothing is a bra. In specific embodiments the handheld device is able to perform a variety of artificial intelligence and machine learning algorithms, including but not limited to image segmentation and classification. In certain embodiments the artificial intelligence and machine learning algorithms are run locally or over cloud.

[0030] Particular embodiments include a method of manufacture of the device of any one of claims, the method comprising: disposing the receptacle on a first layer; forming one or more fluidic channels through the first layer and the receptacle. In some embodiments the method further comprising disposing the at least one wicking element and a sensor on the second side of the receptacle, wherein the at least one wicking element is in fluidic communication with the one or more fluidic channels, wherein the sensor is in fluidic communication with the wicking element. In specific embodiments the method further comprises fabrication of the sensor. In certain embodiments, fabricating the sensor comprises: providing graphene on to a polyimide polymeric sheets (PI), wherein providing includes laser engraving method. In certain embodiments fabricating the sensor further comprises: drop casting Ag and / or AgCl ink; sealing the metal 104905-3262-5274, v. 1electrode and counter electrode; electrodepositing a semi-conductive layer; and drop casting an enzymatic membrane.

[0031] Particular embodiments include a method comprising positioning the device of any one of claims, to a breast of a user during a period of lactation; collecting human milk in the device of any one of claims. In some embodiments the method birther comprises delecting at least one biomarker. In specific embodiments the method further comprises reading a result on the device. In certain embodiments the detecting takes place in a processing unit, and wherein the processing unit is external to the device. In particular embodiments detecting at least one biomarker and / or medicinal is carried out continually over several hours. In some embodiments detecting at least one biomarker and / or medicinal is carried out over several minutes. In specific embodiments the method birther comprises removing the device bom the breast and drying the device. In certain embodiments the method birther comprises removing the device from the breast of a user and placing it in separate device for processing. In particular embodiments the processing comprises heating, sonication, rotation, and / or centrifugation.

[0032] Specific embodiments include a system comprising a device of any one of claims and at least on processing unit. Certain embodiments include a system comprising: a compufing device operably coupled to the device of any one of claims, wherein the computing device comprises at least one processor and memory, the memory having computer-executable instructions stored thereon that, when executed by the at least one processor, cause the at least one processor to: perform the method of any one of claims 99 to 105. In particular embodiments detecting at least one biomarker may carried out using artificial intelligence and machine learning models, including but not limited to image segmentation and classification. Certain embodiments include a device comprising: a pad comprising a plurality of layers, wherein the pad is configured to be worn against a mammary gland of a user; and a channel, wherein the channel is configured to collect a biofluid secreted from the mammary gland of the user. In particular embodiments the pad is configured to form a concave shape when placed against a mammary gland of the user. In some embodiments the pad comprises a generally circular shape. In specific embodiments the pad may be a geometric shape such as a circle, oval, or complex polygon. In certain embodiments a portion of a geometric shape, such as a circle, oval, or complex polygon, may be removed or modified to create a design that more effectively conforms to the anatomical contours of the breast.

[0033] In particular embodiments the pad comprises one or a plurality of cutouts that extend partially or completely extends through all layers of the device. Some embodiments birther comprise a sensor configured to analyze the biofluid secreted from the mammary gland of the user. In specific embodiments the sensor is configured to detect one or more of: anion, an organic molecule,114905-3262-5274, v. 1a medication or drug, a nucleic acid, an antibody, a protein, an antigen, a bacteria, a virus, a parasite, a fungus, a mineral, a vitamin, a lipid, and a hormone. In specific embodiments the sensor is configured to measure a composition of the biofluid secreted from the mammary gland of the user. In certain embodiments the channel is a first channel in a plurality of channels; and the plurality of channels are configured to provide a fluidic coupling between the mammary gland of the user and the sensor. In particular embodiments the plurality of layers comprises a first layer, a second layer and a third layer; and the channel traverses the first layer, the second layer and the third layer. In some embodiments cutouts may be made in each layer to manipulate fluidic connection of layers in the device. In specific embodiments the first layer is a fluid permeable layer; and the third layer is a fluid impermeable layer. In certain embodiments the second layer is an absorbent layer. In particular embodiments the second layer may include adhesives to facilitate attachment to the article of clothing. In some embodiments the second layer may include a removable strip at the back that exposes the adhesive. In specific embodiments the pad comprises a fluid inlet configured to direct the biofluid secreted from the mammary gland of the user to the channel. Certain embodiments further comprise a fluidic barrier surrounding the fluid inlet. In particular embodiments the fluidic barrier is generally circular in shape. In certain embodiments, the device may comprise two separate components configured to be joined together by a user prior to use. In some embodiments, one of the components may include or house a standard or conventional lactation pad.

[0034] In particular embodiments the device comprises: a hollow structure configured to accommodate the mammary papilla; at least one skin-contacting layer; and, one or more openings that provide a fluidic connection between the skin-contacting region and a fluidic layer. In particular embodiments, the hollow structure facilitates sensitive-skin protection, biofluid sampling, targeted fluid routing, or any other functional requirement of the device. In particular embodiments, the at least one skin contacting layer is comprises at least one additional layer designed to enhance comfort, breathability, mechanical compliance, moisture management, and / or secure attachment to the skin. In particular embodiments, wherein the fluidic layer 710 may collect, wick, or transport biofluid — such as breast milk, interstitial fluid, sweat, or any combination thereof — Io at least one sensor 712 for chemical, biochemical, electrochemical, optical, or mechanical analysis. In particular embodiments, further comprise a processor that is electrically and / or fluidically coupled to the sensor. In particular embodiments, the processor may perform any of the following functions: signal processing; analog or digital filtering; amplification; application of current or voltage waveforms; wireless or wired power transfer; wireless or wired data communication; on-device computation; local data storage; sensor 124905-3262-5274, v. 1calibration; temperature compensation; timing control; or activation of valves, pumps, or dissolvable membranes. In particular embodiments, the device comprises one or more barrier layers 718 configured to enhance mechanical integrity, provide insulation or dielectric barriers, protect internal components, increase robustness against bending or compression, or otherwise support the structural or functional operation of the device. In particular embodiments, the processor is communicatively coupled to coils, antennas, or other electronic structures enabling wireless communication (e.g., RFID, NFC, Bluetooth), inductive power transfer, resonant sensing, or additional electronic functionalities. In particular embodiments, the device may additionally include at least one colorimetric sensing region fluidically connected to the fluidic layer. In particular embodiments, wherein, the device may include a color indicator chart positioned on the device surface to enable quantitative or semi-quantitative biomarker analysis by visual comparison or by digital imaging via a smartphone or external reader. In particular embodiments, further comprise one or more fluidic processing layers. In particular embodiments, wherein the skincontacting layer or the barrier layer contain openings that allow fluid to exit or enter the device. In particular embodiments, the barrier layer includes one or more openings that permit controlled fluid release or transfer, facilitate user comfort, or enable active breastfeeding while the device remains in place. Some embodiments, further comprise a removable strip located at any suitable region of the device. Some embodiments, further comprise one or more regions configured to store or preserve biofluid for later analysis, archival, or shipment to a processing center. In particular embodiments, the fluidic layer is introduced through hollow channels or structural conduits within the device.

[0035] Embodiments of the invention accordingly comprises the several steps and the relation of one or more of such steps with respect to each of the others, and the apparatus embodying features of construction, combinations of elements and arrangement of parts that are adapted to affect such steps, all is exemplified in the following detailed disclosure, and the scope of the invention will be indicated in the claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary 134905-3262-5274, v. 1fee.

[0037] FIG. 1 depicts the prior art lactation pad.

[0038] FIGS. 2-5 depict illustrative embodiments of an exemplary device according to some aspects of the disclosure.

[0039] FIG. 6 depicts a photograph of an exemplary method of using an exemplary device according to some aspects of the disclosure.

[0040] FIGS. 7-33 depict illustrative embodiments of an exemplary device according to some aspects of the disclosure.

[0041] FIG. 34 depicts a photograph of an exemplary method of device fabrication according to some aspects of the disclosure.

[0042] FIG. 35 illustrates exemplary wearable, sensor-integrated lactation pads and their electrochemical performance. Panels A-C show fluid-flow behavior upon addition of 400 pL of dyed breast milk. Panel D presents cyclic voltammograms following addition of a 2.0 mM [Fe(CN)6 ’ / 4’ solution. Panels E-G show I-t responses of human milk (pristine and glucose-spiked) from different lactation stages. Panel H provides glucose calibration curves, while Panel I shows current-time traces for varying glucose additions. Panel J presents relative current responses after different soaking durations. All I-t measurements were conducted at 0 V, with SD representing three measurements.

[0043] FIG. 36 shows an embodiment of electrochemical sensors in this disclosure where the sensor contains two working electrode (WE) sensing zones, one reference electrode (RE), and one counter electrode (CE).

[0044] FIG. 37 each panel shows as discussed: (A) The mechanism of work of the developed Glucose biosensor. (B) I-t amperometric responses for the glucose biosensor toward glucose in PBS solution. (C) The calibration curve of the glucose sensor in PBS soludon. (D) I-t amperometric responses for the glucose biosensor toward glucose in artificial milk (aMilk) solution. (E) The calibration curve of the glucose sensor in aMilk solution. (F) Batch-to-batch variability of the produced glucose biosensor. (G) Selectivity of the glucose biosensor toward glucose in the presence of interfering milk components. (H) Shelflife measurements of the biosensor after storage for different periods of time. I-t measurements were conducted at 0 V potential and standard deviation represents three different measurements.

[0045] FIG. 38 shows the fabrication process of the LIG electrodes and the oxidation of acetaminophen on the surface of the working electrode.

[0046] FIG. 39 shows square-wave voltammetry (SWV) characterization of acetaminophen in144905-3262-5274, v. 1buffer and human milk. Panels A-B present raw and background-corrected SWVs at 10 pM acetaminophen, while Panel C shows pH-dependent SWVs across pH 1.8-9.7. Panel D provides a PBS calibration curve (0.1-50 pM), and Panel E shows the corresponding oxidalion-polenlial-pl I relationship. Panels F-G display raw and corrected SWVs for 200 pM acetaminophen in 6-month milk, and Panel H shows the linear dependence of oxidation peak current on the square root of scan rate for 70 pM acetaminophen in milk.

[0047] FIG. 40 depicts a schematic of an exemplary device according to some aspects of the disclosure.

[0048] FIG. 41 illustrates acetaminophen detection in breast milk using a smart nursing -bra pad with FIG electrodes and filter-paper interfaces. Panels A-B show fluid distribution at 0 and 30 s after adding 300 pF of dyed 6-month milk with 4 mMPanel C confirms electrode contact via cyclic voltammetry. Panels D-E present SWVs and calibration curves for varying acetaminophen concentrations in 6-month milk. Panel F shows recovery measurements at 200 pM acetaminophen across 1-, 6-, and 12-month milk. Panels G-I demonstrate reproducibility across electrodes, bending cycles, post-loading intervals, and electrode storage.

[0049] FIG. 42 shows an acetaminophen continuous monitoring study. A. Device design. B. Two minutes after drop casting 200 uE of 6-month breast milk sample, dyed yellow, onto the bra pad, showing the channel is filled with liquid. C. Ten minutes after applying 200 pF of the blue-dyed 6-month breast milk sample, deinonslrali ng the channel is fully refreshed with the new sample. D. Continuous measurement of 70 uM acetaminophen in 6-month breast milk using modified FIG electrodes integrated into the bra pad. E. Calibration of acetaminophen levels in 6-month breast milk using the modified FIG electrodes integrated into the bra pad. F. Pharmacokinetics of acetaminophen measured by the modified FIG electrodes in 6-month breast milk samples, with varying acetaminophen concentrations.

[0050] FIGS. 43-46 depict illustrative embodiments of an exemplary device according to some aspects of the disclosure.

[0051] FIG. 47 shows electrochemical sensing of acetaminophen in milk using fiber-based electrodes (SSf, C-SSf, and C-AuNP-SSf). Panels A-C present SWVs, calibration, and reproducibility in pH 7 buffer using C-AuNP-SSf. Panels D-F show corresponding measurements in 6-month breast milk. Panels G-H illustrate SWV performance and calibration using a fully yam-based system incorporating fiber electrodes for working, reference, and counter functions. Panel I compares responses of the yam-based system in 1- and 12-month milk samples at 74.10 pM acetaminophen.154905-3262-5274, v. 1

[0052] FIG.48 shows integrated measurements in milk using fiber-based electrodes. (A) Schematic of the integrated yam-based sensor with a hydrophilic gauze over the sensing zone for improved milk sampling and sensing. (B) Square wave voltammograms (SWVs) of integrated sensors measured in 166.4 pM acetaminophen in 6-month milk. The three colors show readout from three different sensor patches.

[0053] FIG. 49 illustrates a series of potential shapes that can conform to the contours of a breast. These shapes are designed to provide comfortable coverage while ensuring flexibility and adaptability to various anatomical forms.

[0054] FIG. 50 illustrates a series of potential shapes that can conform to the contours of a breast, each featuring strategically placed outlets and out-cuts to enhance comfort, flexibility, and functionality.

[0055] FIGS. 51-56 depict illustrative embodiments of an exemplary device according to some aspects of the disclosure.

[0056] FIG.57 shows the dependence of color intensity on target biomarker levels in breast milk, measured using colorimetric sensors integrated into exemplary device embodiments.

[0057] FIGS. 59-60 show the characterization and accuracy of K+and Na+sensors, as well as the integrated reference electrode, embedded in exemplary device embodiments for ion measurements in human milk for mastitis diagnosis.

[0058] FIG. 61 shows the characterization and accuracy of Li+sensors, as well as the integrated reference electrode, embedded in exemplary device embodiments for ion measurements in human milk.

[0059] FIGS. 62-67 depict illustrative embodiments of an exemplary device according to some aspects of the disclosure.

[0060] FIG. 68 depicts an exemplary system diagram of a lactation cover.

[0061] FIG. 69 depicts an exemplary flow chart depicting an exemplary method of analyzing breast milk.

[0062] FIG. 70 depicts an exemplary system diagram of a dry milk card, or sample collection for off-site analysis.DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0062] The current invention can be more easily understood by referring to the de -tailed description, examples, drawings, and claims provided, along with their preceding and subsequent explanations. However, prior to discussing the articles, systems, and / or methods described, it should164905-3262-5274, v. 1be noted that this in vention is not confined to the specific or illustrative aspects presented unless explicitly stated, as these aspects can naturally differ. Additionally, it should be acknowledged that the terminology used is intended solely to describe particular aspects and is not meant to be restrictive.

[0063] Each and every feature described herein, and each and every combination of two or more of such features, is included within the scope of the present invention, provided that the features included in such a combination are not mutually inconsistent.

[0064] The description provided below serves as an enabling guide to the invention in its most effective, currently known form. Experts in the relevant field will under-stand that numerous modifications can be made to various aspects of the invention while still achieving its beneficial outcomes. It will also be evident that some of the invention’ s advantages can be realized by using certain features without the need for others. Therefore, those with ordinary skill in the field will recognize that many adjustments and customizations of the invention are both possible and potentially beneficial in specific scenarios, all of which fall within the scope of the invention. Consequently, the following description is presented to illustrate the principles of the invention, not to limit them.

[0065] All patents and publications mentioned in the specification are indicative of the levels of skill of those skilled in the art to which the invention pertains. References cited herein are incorporated by reference herein in their entirety to indicate the state of the art as of their filing date, and it is intended that this information can be employed herein, if needed, to exclude specific embodiments that are in the prior art.DEFINITIONS

[0066] As used herein, the term “subject” refers to any animal (e.g., a mammal), including, but not limited to, humans, non-human primates, rodents, and the like. Typically, the terms “subject” and “patient” are used interchangeably herein in reference to a human subject.

[0067] In this context, the singular terms “a,” “an,” and “the” should be interpreted to include their plural forms unless explicitly stated otherwise. For instance, mentioning a “device” or an “electrode” encompasses scenarios involving two or more such devices or electrodes, unless the context clearly specifies otherwise.

[0068] In additional aspects, the terms “wicking element” and “microfluidic channel” may be used interchangeably as described here. A wicking element is characterized by its capability to draw fluid without the assistance of a pump. It is acknowledged that a wicking element can be referred to as a microfluidic channel. However, it is also recognized that not all microfluidic 174905-3262-5274, v. 1channels possess the wicking property (i.e., the ability to pull fluid without a pumping mechanism or any external force).

[0069] In this context, the terms “optional” or “optionally” indicate that the event or condition being described may or may not take place, encompassing both situations where the event or condition happens and where it does not. In this specification’s description and claims, the term “comprise” and its variations, such as “comprising” and “comprises,” signify “including but not limited to” and are not meant to exclude other components, segments, elements, or steps. Additionally, it should be under-stood that “comprise,” “comprising,” and “comprises,” as they pertain to different aspects, elements, and features of the disclosed invention, also encompass the more restrictive meanings of “consisting essentially of’ and “consisting of.”

[0070] The terms “for example,” “such as,” and their grammatical equivalents are implicitly followed by the phrase “and without limitation,” unless explicitly stated otherwise. Additionally, these phrases are intended solely for illustrative purposes. The term “exemplary,” as used in this context, means “an example of’ and is not meant to indicate a preferred or ideal embodiment.

[0071] Unless specified otherwise, all technical and scientific terms used here have the same meaning as commonly understood by someone with ordinary skill in the relevant field of this invention. Throughout this specification and in the following claims, certain terms will be referenced and defined accordingly.

[0072] The term “or” should be understood as “and / or.” When ranges of values are provided, they are intended as a concise way to refer to each individual value within the range unless stated otherwise, with each specific value incorporated here as if listed individually. All range endpoints are included within the range and can be combined independently. Unless specified otherwise or clearly contradicted by the context, all methods described here may be carried out in any appropriate sequence. When a range is provided, it is understood to include both the lower and upper values specified. For example, the range “x to y” includes x, y, and all values there between. Similarly, the phrases “x, y, z, or less” and “x, y, z, or greater” are intended to encompass the specific values listed, approximate values (“about x,” “about y,” “about z”), and all values less than or greater than the specified values, respectively. Additionally, a range expressed as “x to y” is understood to include “about x to about y.”

[0073] The expressions “ambient temperature” and “room temperature” as used herein are understood in the art and refer generally to a temperature from about 15 °C to about 40 °C.

[0074] Numerical values and ranges in this disclosure are approximate, with specific examples reported as accurately as possible but subject to measurement error. Any184905-3262-5274, v. 1combination of provided values may be used, and ranges described as “about” include the endpoints and all values in between. It is understood that the term “between,” when used in the context of ranges, encompasses the boundary values of the range. For instance, a range stated as between 10 and 15 includes both 10 and 15, unless otherwise specified. This range format is provided for convenience and should be interpreted flexibly. It encompasses not only the explicitly stated numerical values at the range limits but also all individual values and subranges within that range, as if each were explicitly recited. For example, a range of “0.1% to 5%” includes 0.1%, %, all intermediate values (e.g., 1%, 2%, 3%, 4%), and all subranges within the stated range (e.g., 0.5% to 1.1%, 2.4% to 5%, 0.5% to 3.2%, 0.5% to 4.4%, etc.).

[0075] The recitation of value ranges herein is intended to serve as a shorthand method of referring to each individual value within the range, unless stated otherwise, and each value is considered incorporated into the specification as if it were explicitly listed. Ranges provided are understood to represent all values within that range. For example, a range of 1 to 50 includes any individual number or combination of numbers from the set consisting of 1, 2, 3, 4, 5, ..., 49, 50, as well as any subranges, such as 10-40, 20-50, or 5-35. Likewise, numerical ranges defined by endpoints include all subranges contained within that range. For instance, a range of 1 to 5 includes subranges like 1-1.5, 1.5-2, 2-2.75, 2.75-3, 3-3.90, 3.90-4, 4-4.24, 4.24-5, as well as broader ranges like 2-5, 3-5, 1-4, and 2-4.

[0076] In still further aspects, when the specific values are disclosed between two end values, it is understood that these end values can also be included. In additional aspects, when a range is provided along with exemplary values, it is understood that any subranges can be formed between any of the exemplary values within the broader range.

[0077] It will be understood that when an element is described as being “connected” or “coupled” to another element, it may be either directly connected or coupled, or there may be intervening elements. However, when an element is described as being “directly connected” or “directly coupled” to another element, no intervening elements are present. Other terms used to describe the relationship between elements or layers should be interpreted in a similar manner (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” “on” versus “directly on”). As used here, the term “and / or” encompasses any and all combinations of one or more of the listed items.

[0078] It will be understood that while the terms “first,” “second,” etc. , may be used to describe various elements, components, regions, layers, and / or sections, these terms should not be interpreted as limiting. They are merely used to distinguish one element, component, region, layer, or section from another. Therefore, a “first” element, component, region, layer, or section 194905-3262-5274, v. 1described herein could just as easily be referred to as a “second” element, component, region, layer, or section without changing the meaning or departing from the teachings of the example embodiments.

[0079] Spadaily relative terms such as “beneath,” “below,” “lower,” “above,” “upper,” and similar expressions may be used for convenience in describing the relationship between one element or feature and another, as shown in the figures. It should be understood that these terms are intended to cover various orientations of the device during use or operation, not just the orientation shown in the figures. For example, if the device were flipped over, elements described as “below” or “beneath” would be positioned “above” other elements or features. Therefore, the term “below” can refer to both an orientation above and below. The device may also be oriented differently (e.g., rotated 90 degrees or in other positions), and the spatially relative terms used should be interpreted accordingly.

[0080] As used herein, the terms “effective,” “effective amount,” or “conditions effective to” refer to the quantity or condition that is capable of achieving the intended function or property for which the effective amount or condition is specified. The exact amount or condition required may vary depending on the embodiment, influenced by factors such as the materials used and the processing conditions applied. Therefore, it is not always possible to define a precise “effective amount” or “condition effective to.” However, it should be understood that an appropriate effective amount can be easily determined by one of ordinary skill in the art through routine experimentation.

[0081] As used herein, the term “substantially” means that the described event or circumstance either occurs completely or generally, typically, or approximately occurs. As used herein, the term “measured” can refer to an exact or precise quantitative measurement in some contexts, while in other instances, it may refer to measuring relative amounts, rates of change, or qualitative data. It is understood that any measured value can be presented in various forms. In certain cases, the data may be presented as a final concentration, a range, a qualitative response such as “yes” or “no,” or in any other form that effectively conveys the desired information.

[0082] Similarly, when the disclosure refers to a device designed to indicate the presence of at least one characteristic of the fluid, the term “presence” is understood to encompass numerical values, visual representations, qualitative responses, and other forms of indication. It is birther understood that, within the specified context, “presence” can also refer to the simple detection of the indicated property, relative amounts of the property, ranges of different amounts, calibrated amounts compared to different reagents or components, or even precise quantities when possible. In other aspects, the term “presence” may also represent ranges such as “low,” “medium,”204905-3262-5274, v. 1and / or “high,” as well as any intermediate ranges. This indication can be made visually through a color scale or through specific wording or numbers, as desired. It is also understood that any representation that aids the device’s wearer in estimating the amount of the indicated property is included in this disclosure.

[0083] It should be understood that the terms “lactation pad”, “nursing bra pads”, “nursing pads”, “breast pads”, “regular pad”, “regular lactation pad”, “regular nursing pad”, and “disposable nursing pads” all can be used to describe a pad worn by a user during lactation. Exemplary embodiments of such pads comprise a water-permeable top layer, an absorbing material in the middle layer, and a water-impermeable third layer. Such pads can be worn by lactating individuals to absorb the milk leaked involuntarily, and to keep the subject’s clothing and skin dry. It should be under-stood that the terms “smart lactation pad”, “smart nursing bra pads”, “smart nursing pads”, “sensor-embedded lactation pad”, “sensor-integrated lactation pad”, “sensor-embedded nursing pad”, “sensor-integrated nursing pad”, “sensor-embedded nursing bra pad”, “sensor-integrated nursing bra pad”, and “LIG-embedded lactation pad” and combinations of the terms described may be used to refer to embodiments of the present invention disclosed herein.

[0084] It should be understood that the terms “a composition of a biofluid” or “a composition of a fluid” can refer to any chemical or physical properties of the fluid such as concentration of a biomarker in the fluid, presence or absence of a biomarker in the fluid, a ratio or specific relationship between two or more biomarkers present in that fluid, and / or a ratio of groups of biomarkers that are structurally similar in that fluid. Non-limiting examples include a ratio of fat to protein, pH of the fluid, reactivity of the fluid to an agent, electrochemical properties of the fluid, open circuit potential of the fluid measured in an electrochemical cell, redox potential of the fluid, the fluid hydrophobicity and / or hydrophilicity, physical properties of the biofluid, including but not limited to, viscosity, temperature, refractive index, flow rate, dielectric constant, polarizability, turbidity, osmolality, color, absorbance and spectroscopic properties, density, electrical conductivity, surface tension, thermal conductivity, boiling point, freezing point, volatility, specific heat capacity, and permeability.

[0085] For the purposes of this disclosure, the term “biomarker” is defined as any measurable substance, structure, or process present in a biological system that indicates normal or pathological conditions, or responses to therapeutic interventions. Biomarkers may include but are not limited to molecules, cells, genes, gene products, enzymes, metabolites, proteins, hormones, lipids, nucleic acids, ions, and other analytes or biological components detectable in the biofluids. The term “biomarker” also extends to digital biomarkers, which are defined as quantifiable 214905-3262-5274, v. 1physiological, behavioral, or clinical parameters that are collected and measured using digital devices, such as wearables, sensors, or mobile health applications. These digital biomarkers represent data that can indicate health status, disease presence or progression, and responses to treatment. Biomarkers, whether traditional or digital, encompass indicators of health, physiological functions, and pharmacological responses, including both endogenous and exogenous substances and signals used in diagnostic, prognostic, or monitoring contexts.

[0086] It should be understood that the terms “side” and / or “sides” as used herein include an exterior or outer surface of a device or apparatus, including for example, a front surface, a rear surface, a top surface and a bottom surface.

[0087] A variety of general-purpose or specialized computing device environments or configurations may be used. Examples of commonly known computing devices, environments, and / or configurations suitable for use include, but are not limited to, personal computers, server computers, handheld or laptop devices, smartphones, multiprocessor systems, microprocessor-based systems, networked personal computers (PCs), minicomputers, mainframe computers, embedded systems, distributed computing environments that incorporate any of the above systems or devices, and similar technologies.

[0088] The computing devices described herein may include communication connections that enable them to communicate with other devices, if desired. These devices can also feature input devices such as a keyboard, mouse, pen, voice input device, touch input device, and others. Additionally, output devices such as a display, speakers, printer, and the like, may be included. These devices are well-known in the art and do not require further detailed discussion.

[0089] Computer-executable instructions, such as program modules run by a computer, can be utilized. Typically, program modules include routines, programs, objects, components, data structures, and the like, that carry out specific tasks or implement particular abstract datatypes. Distributed coinpuling environments can be employed, where tasks are executed by remote processing devices connected via a communications network or other data transmission medium. In such environments, program modules and other data may be stored both locally and remotely, across various computer storage media, including memory storage devices.

[0090] In its simplest configuration, a computing device generally includes at least one processing unit and memory. Depending on the specific configuration and type of device, the memory may be volatile (random-access memory (RAM)), non-volatile (read-only memory (ROM), flash memory, etc.), or a combination of both. Computing devices can include additional features or functionalities. For instance, a coinpuling device may have extra storage (either removable or non-removable), such as magnetic or ophcal disks, or tape. A computing 224905-3262-5274, v. 1device typically includes various types of computer-readable media. Computer-readable media refers to any available media that can be accessed by the device, encompassing both volatile and nonvolatile media, as well as removable and non-removable media.

[0091] Computer storage media encompass both volatile and non-volatile, as well as removable and non-removable, media used to store information in any method or technology. This includes computer-readable instructions, data structures, pro-gram modules, or other types of data. Examples of computer storage media include memory, removable storage, and non-removable storage. Specific examples are RAM, ROM, electrically erasable programmable read-only memory (EEPROM), flash memory or other memory technologies, CD-ROM, DVDs, and other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage, or any other medium capable of storing and being accessed by a computing device. Any of these types of computer storage media can be integrated into a computing device.

[0092] The computing devices described herein may include communication connections that enable the device to interact with other devices. These connections can be either wireless or wired. Additionally, computing devices may feature input devices such as a keyboard, mouse, pen, voice input device, touch input device, and others. Output devices, including displays, speakers, printers, and similar devices, can also be incorporated. All these devices are well-known in the art and need not be discussed at length here.

[0093] It should be understood that the various techniques described herein can be implemented using hardware components, software components, or a combination of both, as appropriate. Examples of hardware components that may be used include Field-Programmable Gate Arrays (FPGAs), Application-Specific Integrated Circuits (ASICs), Application-Specific Standard Products (ASSPs), System-on-a-Chip (SoC) systems, Complex Programmable Logic Devices (CPLDs), and others. The methods and apparatus of the present disclosure, or certain aspects or portions of them, can be embodied as program code (i.e., instructions) stored on tangible media such as CD-ROMs, hard drives, or other machine-readable storage devices. When this program code is loaded into and executed by a machine, such as a computer, the machine becomes an apparatus capable of practicing the disclosed subject matter.

[0094] Additionally, it is understood that the devices described herein can communicate with other computerized devices through various methods. In some aspects, the sensors may transmit data to computerized devices equipped with cameras or other devices designed to capture a visual response from the measuring device. In other aspects, when the measuring device’s response involves a color change, it is understood that this change can occur within the visible light spectrum.234905-3262-5274, v. 1

[0095] However, it is also understood that the measuring response device may operate in the UV or IR spectra. In these cases, the response can be further analyzed using addilional methods, and the final result can be presented to the device wearer. Furthermore, it is recognized that the response of the devices described herein may include photo fluorescence, fluorescence, and / or luminescent reactions.

[0096] Although aspects of the present invention may be described and claimed under a specific statutory class, such as the system class, this is done for convenience only. One of ordinary skill in the art will recognize that each aspect of the invention can be described and claimed under any appropriate statutory class. Unless explici ( I y stated otherwise, it is not intended that any method or aspect described herein require its steps to be performed in a particular order. Therefore, if a method claim does not specifically state that the steps must follow a particular sequence, no such order should be inferred. This applies to any possible non-explicil interpretations, including logical arrangements of steps, grammatical structure, punctuation, or the number and type of aspects presented in the specification.

[0097] For simplicity, the attached figures do not depict all possible ways (which would be easily recognized by one of ordinary skill in the art based on this disclosure) in which the disclosed system, method, and apparatus can be integrated with other systems, methods, and apparatuses. Additionally, terms like “produce” and “provide” are used to describe the disclosed method, but these are high-level abstractions of the actual operations performed. The specific operations corresponding to these terms may vary depending on the particular implementation and, as indicated in this disclosure, would be readily understood by one of ordinary skill in the art.

[0098] The present invention can be more easily understood by referring to the following detailed description of various aspects of the invention, the examples provided, and the Figures along with their preceding and subsequent descriptions.DEVICE

[0099] In some aspects, disclosed herein is a device comprising: a pad that can be worn against a body, where the pad comprises more than one layer, one or more fluidic channels and a receptacle, wherein the fluidic inlets are positioned in close proximity to the mammary glands and are configured to collect, store, and / or transfer fluids released from the mammary ducts and / or mammary papilla. In certain embodiments of the device, the fluidic channels can transport the fluid to a sensing zone, wherein the device is configured to analyze a composition of the biofluid, and / or the health of the subject, and / or the health of the mammary glands. In certain embodiments of the device, the receptacle can contain an absorbing material where this material 244905-3262-5274, v. 1can absorb large volumes of leaked milk, while some of this leaked milk is directed to a sensing and / or storage zone via embedded fluidic channels. In such exemplary aspects, the device absorbs the excess leaked milk to keeps the skin dry, and to protect the subject’s clothing against gelling wet, while at least performing of the following functions: (1) analyzes a coinposilion of the biofluid, and / or the health of the subject, and / or the health of the mammary glands, (2) processes and stores the biofluid in channels allowing for off-device analysis of the biofluid composition.

[0100] Referring to FIG. 2, the exemplary device 100 as shown includes a first layer 101, a second layer 102, and a third water impermeable layer 103, forming a layered pad, the pad having a fluidic channel 104 traversing first layer 101, second layer 102, and third layer 103. During use, the pad is worn against a body 107 in proximity to the mammary glands. A biofluid 106 secreted from the mammary glands can be captured by the fluidic channel 104. A fluidic barrier 105 can be incorporated to fluidically separate the fluidic channel from the second layer 102. In certain device embodiments, the second layer 102 can be an absorbing material and the third layer 103 can be a water-impermeable and / or water-resistant layer. In some device embodiments, the first layer 101 and the second layer 102 include cutouts (e.g. wherein sections of material are cut or removed in a generally radial pattern from the outer circumference of the pad toward the center of the pad). The cutouts can allow the pad to conform to the body 107 (e.g. mammary gland of the user) and enable fluidic connection between the mammary gland and fluidic channel 104. In the illustrated embodiment, fluidic channel 104 is adjacent to the third layer 103, and can store the secreted biofluid. As depicted in FIG. 2B, the fluidic layer 104 can be removable after it contain the fluid, and can be analyzed off the device. In certain device embodiments as depicted in FIG. 2B, the fluidic layer 104 can have a gripable portion 108 that allows the subject to detach a portion or all of the fluidic layer 104 from the device. This layer can be removable in some embodiments of the device. In certain device embodiments as depicted in FIG. 2B, the fluidic layer 104 can have a perforated section 109 that facilitates detachment of all or a portion of the fluidic layer.

[0101] Referring to FIG. 3, the exemplary device 100 as shown includes a first layer 101, a second layer 102, and a third water impermeable layer 103, forming a layered pad, the pad having a fluidic channel 104 traversing the first layer, the second layer, and the third layer. The pad is worn against a body 107 in proximity to the mammary glands. In some embodiments, the first layer 101 and the second layer 102 include cutouts that enable fluidic connection between the mammary glands and the fluidic channel. The fluidic channel is adjacent to the third layer 103, and a sensor 108 that can analyze the biofluid composition. The device further includes a 254905-3262-5274, v. 1hydrophobic fluidic barrier 105 that separates the fluidic channel 104 from the absorbing material 102. The absorbing material 102 absorbs the excess leaked biofluid to maintain a comfortable dry feel against the subject’s skin. In such exemplary device with fluidic separation between 102 and 104, the separation enables at least one of the following unique functions: (1) the fluid directed to the fluidic channel 104 can undergo processing without concern for reagents used in fluid processing to contact the subject’s skin. (2) the absorbing material may alter the composition of the biofluid making it unsuitable for analysis. The fluidic separation between 102 and 104 avoids such fluid contamination by the absorbing material, while still enabling the wearer to use the pad for prolonged periods with a comfortable, dry skin sensation. (3) The absorbing material 102 may alter the fluid path without fluidic barriers and negatively affect the fluid storage or analysis.

[0102] The vertical layered view of the discussed exemplary device 100 is shown in FIG. 4, where a fluid inlet 101 (placed adjacent to the mammary glands and / or mammary papilla), a layered structure 103 that constitute multiple layers itself, a fluidic barrier 102 that fluidically separates the fluid inlet 101 from the layer 103, a fluidic channel 104 that is adjacent to a sensor 105. The layer structure 103 may contain a fluid permeable layer 1, a layer 2, and a fluid impermeable layer 3, where layer 2 maybe an absorbing material.

[0103] Now ref erring to FIG.5, the exemplary device 100 as shown includes an inlet 101 (placed adjacent to the mammary glands and / or mammary papilla), a layered structure 103 that constitute multiple layers itself, a fluidic barrier 102 that fluidically separates the fluid inlet 101 from the layer 103, a fluidic channel 104 that is adjacent to a sensor 105, and a another layer 106 that can fully or partially cover the sensor 105 and fluidic layer 104. The layer 106 may be a water-impermeable layer. The layer structure 103 may contain a fluid permeable layer 1, a layer 2, and a fluid impermeable layer 3, where layer 2 maybe an absorbing material.

[0104] Referring to FIG. 6, the schematic of the exemplary device 100 as shown includes a layered structure, with the fluidic inlet 102 which will be in proximity to the mammary glands and / or mammary papilla when the pad is worn, a fluidic channel 104 traversing the pad layers, a hydrophobic fluidic barrier 101 that separates the fluidic channel 104 from the absorbing material 103, and a sensor 105 that is in proximity to the fluidic channel 104. In this schematic, the color is used to illustrate the fluid path and is not intended to limit the visual appearance of the collected fluid. The skin interfacing side of the pad is soft and comfortable, while the sensor 105, and fluidic channel 104 are placed over the water impermeable layer at the back of the pad, away from the subject’s skin. In this exemplary device (as shown in FIG. 6) not intended to be limiting, an electrochemical sensor is depicted.264905-3262-5274, v. 1

[0105] Referring now to FIG. 7, the exemplary device 100 as shown includes a processing unit 105 that is placed on the back of the pad. This processing unit 105 may be visible to the subject and can be detachable from the device and / or reused. Such a processing unit can be coupled and / or connected to the sensor 103 for data processing, performing analysis, and / or for coupling with a personal mobile device 107 for wireless (106) or wired data transmission, data storage, and data visualization. The exemplary device 100 can be worn underneath a clothing article not to be limiting such as a bra, and may contain a removable strip 104 to expose an adhesive that enhances the device attachment to the clothing article. The processing unit 105 can be a rigid or flexible circuit. In this exemplary device 100 as shown in FIG. 7, 102 represents a fluidic channel, and 101 represents the back of the pad that does not contact skin.

[0106] Referring now to FIG. 8, the exemplary device 100 as shown includes a processing unit 105 that may be rechargeable or battery-free. In embodiments where the unit is rechargeable, the battery may be recharged using wired and / or wireless methods, including, but not limited to, the use of a near field communication (NFC) protocol. An external device, such as a smartphone, may both charge the battery wirelessly and retrieve data simultaneously. In embodiments where the unit operates without a battery, an external device, such as a smartphone, may supply power to the circuit via near field communication (NFC) when in close proximity, providing sufficient energy for multiple runs and simultaneous data retrieval.

[0107] Referring now to FIG. 9, the exemplary device 100 as shown includes a processing unit 107 that may not be visible to the subject and may be integrated in the layers of the pad. In such exemplary embodiments, any of the following components may be covered with an additional layer in the device and may not be accessible and / or visible to the subject: (1) the processing unit 107, (2) the sensor 106, (3) the fluidic channel 105, (4) the fluidic barrier 106. Referring now to FIG. 10, the exemplary device 100 further comprises one or more inductive coils configured to facilitate wireless power transfer. In certain embodiments, the coils are arranged to enable inductive or resonant coupling with an external power source, thereby supplying energy for device operation, sensor activation, signal processing, or wireless data communication. The inductive coils may be integrated within or adjacent to the device substrate, encapsulated within polymeric or elastomeric layers, and electrically connected to internal circuitry to support autonomous or semi-autonomous functionality.

[0108] Referring now to FIG. 11, the exemplary device 100 as shown can couple with a clothing article which can secure the processing unit 107. The pad 102 is worn alongside an article of clothing 101, and may contain portion of sensors and / or electrical connections that protrude the pad, as shown by 106. In an example not intended to be limiting, the article of 274905-3262-5274, v. 1clothing can be a bra or a nursing bra. The article of clothing can be provided to the subject as part of the claimed device. The exemplary article of clothing can include embedded electrical connections (104) and electrical channels on the clothing, and a secure pocket to contain the processing unit 107. The electrical connections 104 can be incorporated using any method known to art, and such connections can be in permanent electrical communicarion with the processing unit 107 or detach from the processing unit 107. In certain embodiments of the device, the electrical connections 104 can be made of conductive yarn that embroidered or stitched or sewn in the article of clothing. The sensor portion that protrudes as shown by 106 can be electrically connected directly to the processing unit, or connected to electrical connections 104 on the article of clothing via specifically designated connectors on the article of clothing. In certain embodiments of the device, this connection can be done via snap-on buttons.

[0109] Referring now to FIG. 12, the exemplary device 100 as shown can be removed from the body, and connected to a processing unit 102. Such a processing unit can be coupled and / or connected to the sensor 103 for data processing, performing analysis, and / or for coupling with a personal mobile device 103 for wireless or wired data transmission, data processing, data storage, and data visualization.

[0110] Referring now to FIG. 13, the exemplary device 100 as shown can be removed from the body, and placed in a processing unit 101 that performs further processing to the collected fluid to enhance the storage and / or analysis of a fluid composition. Such processing not intended to be limiting includes: centrifugation, rotation, vibration, dispensing reagents, applying energy in form of sound, ultrasound, light, radiation, magnetic, voltage. The processing unit 101 may also measuring energy in form of light, radiation, sound, ultrasound, electrical current, fluorescence, luminescence, take a photo of the device and couple with a personal electronic device for data processing, performing analysis, data storage, and / or data visualization.

[0111] Referring now to FIG. 14, FIG. 15, and FIG. 16, the device may have various sensors embedded in the wearable device. By way of example, colorimetric and lateral flow assays may be incorporated into the device. The resulting data can be processed and interpreted by a processing unit, such as a personal mobile device equipped with camera ftinctionality, to analyze the outcomes of the colorimetric or lateral flow assay. The colorimetric sensors may include a single analysis zone (as shown in FIG. 14) or multiple analysis zones (as shown in FIG. 15) configured for the simultaneous analysis of multiple biomarkers. In the device 100 embodiments as shown in FIGs.14, 15, and 16, 101 is a first layer contacting skin and a body 107, 102 is a second layer that may consist of an absorbing material, 103 is a water impermeable third layer 103, 104 is afliridic channel traversing the first layer, the second layer, and the third layer, 105 is a hydrophobic fluidic 284905-3262-5274, v. 1barrier 105 that separates the fluidic channel 104 from the second layer 102, a sensor 108 that is adjacent to the fluidic channel 104, where the sensor can analyze a composition of the biofluid 106.

[0112] Referring now to FIGs. 17 and 18, the exemplary device 100 as shown includes may integrate the sensing zones in the fluidic layer 104, and a separate sensing component and / or layer may not be used in the device.

[0113] It should be noted that the shape and dimensions of the fluidic channels shown in illustrations are an example of a device embodiment and are not intended to be limiting. Referring now to FIG. 19, the exemplary device 100 can include a fluidic layer 104 that splits the fluid into multiple zones and directs the fluid to multiple embedded sensing zones 105 for fluid analysis. In the depicted exemplary device 100, 101 a fluid inlet (placed adjacent to the mammary glands and / or mammary papilla), 102 a layered structure 103 that constitute multiple layers itself, and 103 are fluid processing layers that do either of the following functions: (1) store one or more reagents for sensing, processing, stabilizing or reacting with components in the biofluid, (2) filtration of biofluid, (3) mixing of reagents into the biofluid, (4) affecting the flow of the biofluid, (3) adding valves and dissolvable membranes for controlling the timing of the assay. The fluid processing layer 103 can have any shape and size and can overlap with the fluidic layer 104.

[0114] Referring now to FIG. 20, artificial intelligence (Al) and machine learning (ML) algorithms, executed on an external device such as a smartphone and / or via cloud processing, are employed for image processing and analysis of one or more colorimetric assays. The algorithm may encompass multiple stages, including image segmentation and classification, as well as other machine learning models, to assess and classify the concentration levels of various biomarkers.

[0115] Referring now to FIGs. 21 and 22, the exemplary device 100 may incorporate one or more colorimetric sensing elements integrated within any layer of the device structure. In certain embodiments, colorimetric sensing zones are embedded within the skin-interfacing layer 101, the hydrophilic transport layer 102, or the water-impermeable layer 103. As depicted in FIGs.21 and 22, in some embodiments the device does not include a discrete fluidic inlet; instead, biofluid such as milk may be passively transported through the hydrophilic layer 102 to the sensing zones by capillary action or wicking. In certain embodiments, the water-impermeable layer 103 is at least partially optically transparent to permit visual observation of color changes within the sensing region. In other embodiments, an optically clear window 110 is incorporated into the device to facilitate visual interpretation of colorimetric responses. The sensing region is configured to exhibit a detectable color change in response to variations in one or more biomarkers 294905-3262-5274, v. 1present in the collected biofluid. In additional embodiments, a color reference chart for qualitative or semi-quantitative evaluation of biomarker concentration may be integrated on the front or back surface of the device, or provided separately to the user for comparison and interpretation. In other embodiments, device might include a removable strip to expose an adhesive for device fixation. In some embodiments, layer 102 can be fiirther modified with at least one fluidic barrier 116 to direct and limit the flow of the fluid.

[0116] Referring now to FIG. 23, the exemplary device 100 as shown includes a fluid inlet 101 (placed adjacent to the mammary glands and / or mammary papilla), a layered structure 103 that constitute multiple layers itself, a fluidic barrier 102 that fluidically separates the fluid inlet 101 from the layer 103, a second fluid barrier 104, a fluidic channel 105 that is adjacent to a sensor 106. The layered structure 103 may contain a fluid permeable layer 1, a layer 2, and a fluid impermeable layer 3, where layer 2 maybe an absorbing material. It should be understood that the order and number of layers and materials depicted in the exemplary device 100 shown FIG.23 is not limiting, and represents one embodiment of the device. In this exemplary device (as shown in FIG. 23) not intended to be limiting, an electrochemical sensor is depicted, but other sensors such as colorimetric, lateral flow, magnetic, distance-based, surface-enhanced Raman (SERS) can also be incorporated.

[0117] Referring now to FIG. 24, FIG. 26, and FIG. 25 the exemplary device 100 as shown includes a fluid inlet 101 (placed adjacent to the mammary glands and / or mammary papilla), a layered structure 103 that constitute multiple layers itself, a fluidic barrier 102 that fluidically separates the fluid inlet 101 from the layer 103, at least one or multiple fluid processing layers 104, a fluidic channel 105 that is adjacent to a sensor 106. The fluid processing layer or layers enhance the fluid collection and analysis via any of the following ftmctions: (1) store one or more reagents for sensing, processing, stabilizing or reacting with components in the biofluid, (2) filtration of biofluid, (3) mixing of reagents into the biofluid, (4) affecting the flow of the biofluid, (3) adding valves and dissolvable membranes for controlling the timing of the assay. The fluid processing layer 104 can have any shape and size and can overlap with the fluidic layer 105. The layered structure 103 may contain a fluid permeable layer 1, a layer 2, and a fluid impermeable layer 3, where layer 2 maybe an absorbing material. It should be understood that the order and number of layers and materials depicted is not limiting, and represents one embodiment of the device. In this exemplary device not intended to be limiting, an electrochemical sensor is depicted.

[0118] While in certain embodiments of the device, a single fluidic inlet was shown, it should be understood that this is not intended to be limiting and more than one inlet can be incorporated in the device to maximize fluid capture. Referring now to FIG. 27, the exemplary device 100304905-3262-5274, v. 1includes multiple fluid inlets 101 (placed adjacent to the mammary glands and / or mammary papilla), a layered structure 103 that constitute multiple layers itself, multiple fluidic barriers 102 that fluidically separates the fluid inlets 101 from the layer 103, a fluidic barrier 104 intended to separate the fluidic channel 105 from 103„ a fluidic channel 105 that includes multiple inlets and is adjacent to a sensor 106. Other embodiments of the such exemplary device with multiple fluid inlets may include other layers for fluid processing to enhance fluid storage and analysis. Now referring to FIG. 28, the exemplary device 100 can include the fluid processing layer 104, where this layer performs any of the following functions: (1) store one or more reagents for sensing, processing, stabilizing or reacting with components in the biofluid, (2) filtration of biofluid, (3) mixing of reagents into the biofluid, (4) affecting the flow of the biofluid, (3) adding valves and dissolvable membranes for controlling the liming of the assay. The fluid processing layer 104 can have any shape and size and can overlap with the fluidic layer 105.

[0119] Now referring to FIG. 29A, the exemplary device 100 includes multiple fluid inlets 101 (placed adjacent to the mammary glands and / or mammary papilla), a layered structure 103 that constitute multiple layers itself, multiple fluidic barriers 102 that fluidically separates the fluid inlets 101 from the layer 103, and a fluidic channel 104. It should be understood that the fluidic channel layer 104 can constitute of a single layer of material that exhibits capillary wicking or made of mul li layers of materials with hollow channels that can be filled with fluid. In the latter arrangement, the fluidic channel includes an inlet 106 that connects the channel to the device fluid inlet 101, atop layer 107, a middle layer 108 with hollow channels that can contain fluids, and a third layer 109 that could include sensing zones. As depicted in FIG. 29B, the fluidic channel 104 can include markings 110 that enable analysis of a composition of the fluid through visual inspection by the subject. It should be understood that the subject may be instructed to place the entire device in a processing unit or remove a portion of the device (such as the fluidic portion of the exemplary device 100 as depicted in FIG.29C) and place it in the processing unit 111 before interpreting the analysis results and markings on the device. The processing unit not intended to be limiting, could process the device with any of the following means: centrifugation, rotation, vibration, dispensing reagents, applying energy in form of sound, ultrasound, light, radiation, magnetic, voltage. The processing unit 101 may also measuring energy in form of light, radiation, sound, ultrasound, electrical current, fluorescence, luminescence, take a photo of the device and couple with apersonal electronic device for data processing, performing analysis, data storage, and / or data visualization.

[0120] Referring now to FIG. 31, the exemplary device 200 as shown includes a first layer 201, a second layer 202, and a third water impermeable layer 203, forming a layered pad, the pad 314905-3262-5274, v. 1having a fluidic channel 204 traversing the first layer, the second layer, and the third layer once, and then traversing the third layer and the second layer again. The pad is worn against a body 207 in proximity to the mammary glands. The fluidic channel 204 is adjacent to the third layer 203, and a sensor 208 that can analyze the biofluid composition. The device further includes a hydrophobic fluidic barrier 205 that separates the fluidic channel 204 from the absorbing material 202. The terminal end of the fluidic channel 204 can be fluidically connected to the absorbing material 202 to use the absorbing material for continuous refreshing the fluidic channel (removing the old fluid and bringing in new fluid) and enabling continuous monitoring capability for the device.

[0121] Referring now to FIG. 30, the exemplary device 200 as shown includes a first layer 201, a second layer 202, and athird water impermeable layer 203, forming a layered pad, the pad having a fluid inlet 210, a fluidic barrier 205 that separates the inlet 210 from any of the layers 201, 202, and 203, and a fluidic channel 204 that is adjacent to a sensor 208. The fluidic layer 204 is fluidically connected to the fluid inlet 205 and to the second layer 202. In certain device embodiments, the layer 202 is an absorbing material that can pump the fluid and / or remove the fluid in the fluidic channel and allowing for new fluid to enter the channel, thus enabling refreshing of the fluidic channel and continuous monitoring with the device. The layer can be covered with an additional layer 209 for aesthetics or functional reasons.

[0122] Referring now to FIG. 32, depicts a photograph of an exemplary device 200 as shown includes a fluidic inlet 201, an absorbing material 203, and a fluidic barrier 202 that fluidically separates the inlet 201 from the absorbing material 203. FIG. 32A shows the front of the pad (contacting skin), where some of the captured fluid is directed in the fluid inlet 201, and excess of the fluid is absorbed by the absorbing material 203. In such exemplary photograph, the blue colored fluid marks the path of the fluid flow and is not intended to be limiting the appearance of the fluid collected and / or analyzed with the device. The fluidic channel 206 captures the fluid from inlet 201 and fransverses the pad layers to contact a sensor 205 that analyzes a composition of the biofluid. The terminal end of the fluidic channel 204 can transverse the water-impermeable layer of the pad a second time to be connected to the absorbing material 202 at its terminal end as depicted in point 206. Such connection allows for refreshing of the fluidic channel 204, and continuous or frequent measurements from the same device.EXAMPLE 1 - Smart Lactation Pad for Glucose Sensing

[0123] This example presents a wearable sensor embedded in a lactation pad for on-body324905-3262-5274, v. 1sampling of breast milk and continuous and / or frequent analysis of glucose levels in breast milk. By integrating microfluidic channels and electrochemical sensors in the lactation pad, milk sampling and analysis becomes part of an existing daily routine for the mother, posing no additional burden for milk sampling and analysis

[0023] , The electrochemical sensors are developed using laser-induced carbonization of polyimide thin films, allowing for development of flexible, low-cost, and high-surface area electrodes. Glucose sensing was done via an enzymatic membrane composed of glucose oxidase, glutaraldehyde, bovine serum albumin, and Nation to achieve enhanced enzyme protection and extended biosensor shelf life and operation in milk. Notably, the wearable device demonstrates high accuracy (96.8 to 104.1%) in measurement of glucose in whole undiluted human milk, collected 1st, 6^, and 12^ months postpartum

[0023] , In some implementation of the device in this study, a smart bra pad is employed to track babies’ glucose intake and potentially identify early signs of health concerns.

[0124] Glucose in breast milk is a vital nutrient that supports infant growth and brain development [24, 25 ] . Higher glucose intake correlates with increased infant weight, length, and BMI

[0026] , raising concerns since milk from overweight or obese mothers contains higher glucose levels

[0027] , potentially reinforcing childhood obesity trends. Conversely, mothers with gestational diabetes exhibit lower milk glucose levels due to impaired insulin sensitivity and altered glucose regulation

[0028] , Untreated neonatal hypoglycemia can cause severe neurological damage, including developmental delays and seizures

[0025] , and while some symptoms are apparent, such as jitteriness or poor feeding

[0029] , asymptomatic cases highlight the need for continuous monitoring of glucose levels in breast milk.

[0125] A platform is developed and capable of sampling breast milk in a wearable device and directing that milk to an electrochemical sensing zone able to measure a wide range of biomarkers. Specifically, a glucose sensing zone is introduced into a wearable smart lactation pad, allowing for either continuous or frequent monitoring of glucose levels in breast milk. Nursing bra pads (FIG. 1) or lactation pads are commonly used by breastfeeding individuals to absorb milk leakage, protect the clothing from stains, and maintain comfort and hygiene throughout the day. Based on this, a user-friendly lactation pad was developed a novel wearable sensor-embedded platform (FIG. 31, and FIG. 32) to collect breast milk and monitor components simultaneously. In this wearable platform, different kinds of elements are integrated (FIG. 33) to realize its function, such as hydrophobic materials to build breast milk gathering area, wicking layer made of cellulose paper to direct sample to measurement site and sensors to collect the electrochemical signal and analyze a composition of the biofluid.334905-3262-5274, v. 1

[0126] For the material of this sensor, laser-induced graphene (LIG) was utilized as electrodes because it is flexible to fit the curve of lactation bra pad and low cost to make the platform at an affordable price point

[0023] , With this wearable sensor-embedded platform, a user can perform a single point measurement by removing it from the body and connecting the device to an analyzer such as a portable potentiostat (FIG. 12), or the user can do continuous monitoring via an analyzer that is mounted on the device either permanently or temporarily (FIG. 9, FIG. 7, and FIG. 11), to transfer data via wireless communication, such as short-range radio frequency protocols, and / or apply current and / or voltage, and / or measure current and / or volt-age for the electrochemical analysis. To realize continuous monitoring, this platform was further developed by connecli ng the wicking layer (cellulose paper) back to the middle absorbent layer in the bra pad (FIG. 32 and FIG. 33). In this case, breast milk was absorbed by the absorbing material in the lactation pad again after flowing through working area of sensor. Because of the absorbing material in the middle layer of the lactation pad and the generated negative pressure, sufficient capillary force was enabled inside the paper to pump breast milk passing the sensor continuously.

[0127] FIG. 33 shows the components of the exemplary smart lactation pad. Front and back of the wearable device are shown in FIG. 33 B and C. The skin inter-facing side of the device is soft and comfortable against skin. A hydrophobic ring separates (204 in FIG. 33A) the general milk absorbing zone from the microfluidic channel (cellulose paper, 206 in FIG. 33A) for milk sampling, and avoids contamination by the absorbing material for the milk that is directed to the sensing zone. The electrochemical sensors(207 in FIG. 33A) are fabricated using laserengraving (Fig. 34) to ensure low-cost of the sensors while maintaining high mechanical stability and flexibility for the sensors (important as lactation pads are pressed to conform to the body shape, subjecting the sensors to mechanical stress). The laser-induced graphene (LIG) electrodes are ftmctionalized with glucose oxidase and a mediator to allow selective detection of glucose in milk (FIG. 34).

[0128] Referring now to FIGs. 21 and 22, the exemplary device 100 may incorporate one or more colorimetric sensing elements integrated within any layer of the device structure. In certain embodiments, colorimetric sensing zones are embedded within the skin-interfacing layer 101, the hydrophilic transport layer 102, or the water-impermeable layer 103. As depicted in FIGs.21 and 22, in some embodiments the device does not include a discrete fluidic inlet; instead, biofluid such as milk may be passively transported through the hydrophilic layer 102 to the sensing zones by capillary action or wicking. In certain embodiments, the water-impermeable layer 103 is at least partially optically transparent to permit visual observation of color changes within the sensing region. In other embodiments, an optically clear window 110 is incorporated 344905-3262-5274, v. 1into the device to facilitate visual interpretation of colorimetric responses. The sensing region is configured to exhibit a detectable color change in response to variations in one or more biomarkers present in the collected biofluid. In additional embodiments, a color reference chart for qualitative or semi -quantitative evaluation of biomarker concentrarion may be integrated on the front or back surface of the device, or, in other embodiments, a separate color chart may be provided to the user for comparison and interpretation.

[0129] In an embodiment, the electrochemical sensors in the device are produced via laser engraving on polyimide polymeric sheets (PI, thickness of 125 pm) using a CO2 laser beam with a wavelength of 9.3 pm. Laser engraving is a scalable, reproducible, and single-step process that forms high-quality graphitic structure without further physical or chemical processing. LIGs have a porous structure with high surface area, excellent electrical conductivity, and outstanding mechanical stability and flexibility, maintaining their electrochemical performance after several bending cycles

[0023] , The structure electrochemical and mechanical properties of produced LIGs are significantly dependent on the delivered laser energy per unit area and the amount of energy delivered. To select and obtain the optimal parameters for engraving, we optimized the laser power and beam diameter at a fixed speed of 20% of the maximum engraving speed of the machine. Here, we optimized engraving conditions to maximize electrical conductivity and electrode surface area (reported

[0023] ). LIG was fabricated using a laser power of 13% and a defocusing distance of 0.30 inch, yielding mechanically stable graphene with a sheet resistance of 7.2 Q / sq. Mechanical durability tests involving repeated 150° bending showed no significant change in sheet resistivity after 50 cycles, confirming the LIG’s robustness and suitability for wearable integration

[0023] ,

[0130] A three-electrode system with a 4 mm working electrode diameter was fabricated under optimized engraving conditions. Electrodes were rinsed, dried, and the reference electrode was prepared using Ag / AgCl ink cured at 60 °C. Electrochemical performance was evaluated by cyclic voltammetry

[0023] , For enzymatic sensing, Prussian Blue (PB, Fe4[Fe(CN)6h) was deposited on the working electrode as a redox mediator

[0023] , Following confirmation of H2O2 response, a glucose oxidase (GOx)-based enzymatic membrane was formed by cross-linking BSA and GOx using glutaraldehyde, with Nation added to enhance selectivity and diffusion. The resulting membrane maintained enzyme activity, improved stability, and minimized interference. At the interface between the biosensor and the solution, GOx catalyzes the oxidation of glucose in the presence of O2 and H2O, yielding gluconic acid and H2O2. On the electrode surface, at a zero or slightly negative potential, Prussian Blue (PB) is reduced to Prussian White (PW). Subsequently, PW reacts with H2O2, reducing it to OI I while being oxidized to regenerate PB. PB is then reduced back to PW, completing a cycle of chemical reactions. The electrochemical 354905-3262-5274, v. 1cathodic current generated in this process corresponds to the produced H2O2, and sequentially the oxidized amount of glucose, allowing for the indirect quantification of glucose concentrarion in the sample.

[0131] Glucose detection was performed using i-t amperometry at a constant potential of 0 V withPB / GOx-modified LIG electrodes. The biosensor showed a clear, concentration-dependent increase in current across 0-5 mM glucose in PBS (FIG. 37B), with steady-state current at 60 s used for calibration (FIG. 37C). A linear response was obtained (slope = -1.27 pA-mM-^, intercept = -0.62 pA, R = 0.996) and a calculated LOD of 0.15 mM. These metrics indicate the sensor’s suitability for quantifying physiological glucose levels (1^4- mM) in human milk.

[0132] The sensor’s practical performance was tested in artificial milk (aMilk) simulating human milk composition, i-t amperometry showed a concentration-dependent increase in current for 0-5 mM glucose (FIG. 37D), with a linear calibration curve (slope = -1.34, intercept = -0.38, FIG.37E). These results confirm the sensor’s linearity and sensitivity are suitable for quantifying glucose in human milk. Batch-to-batch variability was evaluated by fabricating five enzymatic sensor batches under different conditions and testing their response to 1 mM glucose in PBS. No significant differences were observed, indicating consistent manufacturing and performance (FIG.37F). Sensor selectivity was confirmed by testing glucose in the presence of potential interferents (choline, inositol, vitamins E, B2, B3, B4, B5); the response remained consistent (FIG. 37G). Selectivity arises from the enzymatic membrane, which blocks interferents, and the 0 V measurement potential, which prevents oxidation or reduction of other components, enabling reliable glucose detection in complex matrices like human milk.

[0133] The wearable lactation pad with integrated microfluidics (FIG. 35A-C) has a 400 pL dead volume that fills within 60 seconds, as demonstrated using a blue dye. Fluid flow and stable contact with the LIG electrode were validated via CV using 2.0 mM [Fe(CN)e]in 100 mM KC1, showing stable signals after 60 s (FIG. 35D). Integrated LIG-based glucose sensors were then tested with breast milk collected at 1, 6, and 12 months postpartum, confirming accurate glucose measurement across varying milk compositions and potential interferents

[0023] , Glucose concentrations in milk samples were measured directly using the calibration curve from aMilk (FIG. 37E) and validated by spiking with 1.0 and 2.0 mM glucose, i-t amperometry (FIG. 35E-G) showed spike recoveries of 96.8-104.1% with SDs of 3.7-8.3%

[0023] , Calibration curves for 1-, 6-, and 12-month milk samples exhibited comparable slopes (-1.37, -1.37, -1.25 pA-inM-'), closely matching the reference aMilk curve (-1.34 pA-inM-'), demonstrating consistent and364905-3262-5274, v. 1accurate glucose measurement across lactation stages despite potential interferents.

[0134] Channel refresh and dynamic glucose monitoring were tested by sequentially adding breast milk spiked with different glucose concenlralions to the smart lactation pad. After adding 200 pL of 1 mM glucose milk, amperometry began at 60 s. Sub-sequent addition of 100 pF of milk with 2 mM glucose or no glucose produced stable current changes within 120 s, demonstrating a temporal resolution of 2 minutes. FIG. 351 shows the sensor’s amperometric response tracking increases and decreases in glucose, confirming the device’s capability for continuous monitoring. Experiments used 1 -month postpartum milk, which has the highest fat content and viscosity. To assess the effect of prolonged milk exposure on sensor performance, sensors were sub-merged in breast milk for 0, 20, 40, and 60 minutes before glucose measurement. Responses remained consistent even after 60 minutes (FIG. 35 J), demonstrating the sensor’s suitability for long-term monitoring and on-body use.

[0135] Experimental procedures, statistical analyses, and material sources are re-ported in

[0023] , Polyimide (Kapton) film was purchased from McMaster-Carr (USA), cleaned sequentially with acetone, 70% isopropyl alcohol, and DI water, and dried at 60 °C for 30 min. The film was then laser-engraved (VLS2.30, 30 W, 9.3 pm wave-length). Prussian Blue (PB) was electrodeposited using i-t amperometry at 0.4 V for 300 s in a soludon of 5 mM FeCE, 5 mM K3Fe[CN]e, 0.1 M KC1, and 0.1 M HC1 with an Ag / AgCl reference electrode. For glucose sensor fabrication, three solutions were prepared: 1% BSA in PBS, 0.5% glutaraldehyde (GA) in DI water, and 0.5% Nation in DI water. Glucose oxidase (4 mg) was dissolved in 100 pF BSA solution, followed by sequential addition of 100 pF GA and 35 pF Nation. Finally, 4 pF of this mixture was drop-cast on the electrode and dried at ambient conditions for 24 hours.EXAMPLE 2 - Smart Lactation Pad for Measurement of Medications

[0136] Medications taken by the mother can also be transferred through milk. Consequently, breastfeeding should generally continue unless a specific drug poses greater risk than benefit

[0011] , highlighting the need for tools that evaluate drug concentrations in milk to ensure safe medication management during lactation. Acetaminophen is the most commonly prescribed postnatal pain medication

[0030] and is also frequently administered to children and neonates

[0031] , creating potential for both direct and milk-mediated infant exposure. While generally safe, improper dosing can lead to severe health issues, including acute liver failure — Ihc leading cause in children — and over 56,000 annual ER visits

[0032] , Infants are particularly vulnerable due to immature fiver fiinction [33, 34], Carefiil monitoring of acetaminophen in nursing mothers is essential to prevent374905-3262-5274, v. 1toxicity, and quantitative measurement of drug levels in breast milk could guide strategies, such as “pump and dump,” to minimize infant exposure.

[0137] There are no tools for frequent point-of-care or at-home monitoring of acetaminophen in breast milk. For research purposes, the gold standard method for quanli lying acetaminophen (and in general for other medications) is high-performance liquid chromatography for separation coupled with mass spectrometry for detection (HPLC-MS)

[0035] , Analysis with HPLC-MS requires extensive sample preparation, expensive solvents, specialized equipment, and is timeconsuming, thus making it in-appropriate for routine use by nursing mothers in an at-home or point-of-care setting. The concentration of medication in milk is often estimated indirectly using the milk-to-plasma ratio, where the drug is measured in blood or blood plasma

[0011] , These calculations are influenced by the variability in the milk-to-plasma ratio, making it inaccurate to use a single value for varying individuals due to biological differences.

[0138] Disclosed herein is the development of a wearable electrochemical sensor designed for rapid and frequent measurement of acetaminophen levels in breast milk, facilitating convenient at-home monitoring. We introduced two designs for milk sampling fluidics: the first enables continuous monitoring throughout the day, providing real-time measurement of acetaminophen release kinetics in breast milk (as depicted in FIG.31). The second, a simpler design, allows for a single measurement, ideal for use just before breastfeeding (as depicted in FIG. 3). The disclosed wearable platform helps parents determine the optimal strategy for “pumping and dumping” (disposing of milk after exposure) by directly measuring acetaminophen concentrations in milk. With this tool, parents can make informed decisions about when to pump and dump, ensuring safe breastfeeding while managing necessary medical treatments, such as those for postpartum pain. The risk of infant drug overexposure is significant, and the American Academy of Pediatrics recommends avoiding acetaminophen for children under three months without healthcare provider supervision

[0036] , Therefore, the developed wearable device addresses this need and technical gap, enabling accurate and non-invasive monitoring to assist healthcare providers and give nursing parents peace of mind.

[0139] The lactation pad-integrated electrochemical sensor measures acetaminophen in breast milk via drug oxidation using square wave voltammetry (SWV) (FIG. 38). The pad features a 5 cm paper-based microfluidic channel that directs milk from the center to the LIG electrode 2.5 cm away, with a hydrophobic ring isolating the channel from the absorbent material (FIG. 41 A-B). Milk travels through the channel in 30 s for full electrode contact. Acetaminophen levels can be monitored continuously via a flexible potentiostat mounted on the pad or measured at single points using a portable or wireless potentiostat connected to a personal device.

[0140] SWV of milk spiked with 200 pM acetaminophen showed a distinct oxidation peak at 280384905-3262-5274, v. 1mV vs. Ag / AgCl, absent in unspiked milk (FIG. 39F). Background current was removed using a third-degree polynomial fit after masking the peak (FIG.39G). Initial studies were conducted with 6-month postpartum milk, and accuracy was subsequently validated in 1- and 12-month samples. Varying acetaminophen concentrations were introduced, and levels were determined using the calibration curve from 6-month milk (FIG. 41F). Recovery values for three concentrations in 1-and 12-month samples were near 100%

[0037] , confirming that the smart lactation pad performs reliably across the breastfeeding period.

[0141] The mechanical and operational stability of the LIG electrodes in the smart lactation pad was evaluated. Currents measured for 70 pM acetaminophen in 6-month milk remained consistent after 50-100 bending cycles (FIG. 41H), after soaking in milk for up to one hour (FIG. 411)

[0037] , and after storage for 35-50 days (FIG. 41 J), demonstrating robustness against mechanical stress, prolonged milk exposure, and long-term storage. The specificity of the electrochemical acetaminophen sensor was tested against common postpartum antibiotics at their maximum breast milk concentrations. Six-month milk samples were spiked with 70 pM acetaminophen and each antibiotic. Minimal deviations in peak current confirmed that the smart lactation pad accurately detects acetaminophen without interference from these commonly prescribed drugs

[0037] ,

[0142] While bare LIG electrodes are highly sensitive, they are single -use. To enable continuous acetaminophen monitoring, a hydrogel membrane of BSA, GA, and Nation was applied to all electrodes. BSA provides a biocompatible matrix, GA stabilizes the structure via crosslinking, and Nation adds charge-selective permeability. This membrane reduces fouling, enhances selectivity, and shifts sensing to a diffusion-controlled regime, enabling stable, continuous measurements. To ensure a constant flow of breast milk within the channel for continuous measurements, the wicking cellulose paper is reintroduced into the absorbent pad, as shown in FIG. 42A. To illustrate the steady liquid flow within the fluidic channel, a 6-month breast milk sample, dyed yellow, is added on the inlet. FIG.42B displays the pad two minutes after the dropcasting, where the channel is filled with the liquid and has reached the end of the flow loop. Two minutes later, a fresh breast milk sample, dyed blue, is introduced, and FIG.42C shows the pad ten minutes after this second addition, demonstrating that the channel has been fully refreshed with the new liquid.

[0143] A dual-working-electrode design (FIG. 36) was implemented for continuous acetaminophen monitoring. Three coated electrodes embedded in the smart bra pad measured the same concentration every 15 minutes over two hours with <10% variation (FIG. 42D). Calibration in 6-month milk showed a sensitivity of 0.066 pA / pM. Using this setup, pharmacokinetics were evaluated by sequentially introducing acetaminophen-spiked milk (25- 394905-3262-5274, v. 1200 pM) with 15 -minute intervals for channel refresh. The electrodes reliably detected both increasing and decreasing concentrarions, confirming effective sample refreshment and continuous measurement capability (FIG. 42F).EXAMPLE 3 - Other Device Embodiments

[0144] It should be understood that the fluid inlet for capture of fluid from mammary gland may be a water permeable layer that covers the entire or a portion of the skin-contacting side of the pad. Referring now to FIG.40, the exemplary device 300 includes at least a water-permeable first layer 301 that is contact with skin and can sample the biofluid 306, a second layer 302, a sensor 304 adjacent to the second layer 302 where the sensor is configured to analyze a composition of the biofluid, and a third water impermeable layer 303. An analyzer 305 can be coupled with the sensor and placed at different layers of the device or transverse the layers in the device. The analyzer 305 can facilitate signal readout from the sensor, power the sensor, or assist in sample processing or analysis of a composition of the biofluid. In certain device embodiments, a removable strip 307 can be incorporated in the third or terminal layer of the device. Such a strip 307 exposes an adhesive that enhances the attachment of the device to a secondary surface not intended to be limiting such as an article of clothing. In certain embodiments of the device the layer 102 can contain an absorbing material, where this material can absorb large volumes of leaked milk, while some of this leaked milk is directed to a sensing and / or storage zone via embedded fluidic channels. In such exemplary aspects, the device absorbs the excess leaked milk to keeps the skin dry, and to protect the subject’s clothing against getting wet, while at least performing of the following fiinctions: (1) analyzes a composition of the biofluid, and / or the health of the subject, and / or the health of the mammary glands, (2) processes and stores the biofluid in channels allowing for off-device analysis of the biofluid composition.

[0145] While any sensor can be incorporated in the device, an exemplary device embodiment includes incorporation of a flexible sensor made of conductive yarn in the pad. Yam and fiberbased materials offer significant advantages for building medical devices and electrochemical sensors. Their inherent flexibility and softness make them ideal for wearables, ensuring comfort and better patient compliance during prolonged use. These materials are lightweight, low-profile, and breathable, which enhances user comfort and supports skin health by allowing moisture management. The high surface area of fibers improves the interaction with analytes in biofluids, boosting sensor sensitivity and response times. Fibers can also be customized with coatings or fimctionalization for detecting various biomarkers, adding versatility to medical404905-3262-5274, v. 1applications. Seamless integration into textiles enables the creation of smart clothing and wearables that blend traditional apparel with advanced sensing functions. Many fibers are biocompatible, reducing skin irritation risks, and some can be made durable and washable, increasing their usability in real-world conditions. Conductive modifications, such as with carbon nanotubes or metal nanoparticles, enhance electrochemical performance, enabling fibers to function effectively as sensor electrodes. Additionally, the scalability and cost-effectiveness of textile manufacturing make fiber-based devices attractive for large-scale production. Finally, using natural fibers promotes sustainability, adding an eco-friendly aspect to medical de-vice development. A low-cost steel fiber with outstanding conductivity (less than 10 Ohm per feet) and mechanical strength is used to develop a flexible sensing array in one embodiment of disclosed device. Noteworthy, the steel fiber is conductive to the core and not plated over a non-conductive backbone, resulting in outstanding mechanical properties and high resilience.

[0146] Now referring to FIG.43, in the depicted exemplary device 400, conductive yarn can be secured to a layer 402 to create a flexible electrode array. A wide range of techniques can be adopted for this purpose including basic stitching methods, such as running stitches or backstitches, satin stitches and zigzag stitches, chain stitches or blanket stitches, cross-stitching, or using embroidered knots. Each technique can be tailored based on the fiber’s characteristics and the intended use of the secured layer, balancing durability, flexibility, and aesthetics. In the exemplary device 400 (FIG. 43), a basic stitch was used for a silver yarn (labeled as 401 in FIG. 43) and couching was used to secure a stainless steel yam to a textile substrate. Couching is an effective technique where a secondary thread (labeled as 403 in FIG.43) is stitched over the fiber at intervals, anchoring it to the layer beneath without piercing the fiber itself. All or a portion of a fiber can be modified with a coating (modification step shown as 405 in FIG. 43) to tune the electrochemical properties of the fiber. In the exemplary device 400 (FIG. 43), the stainless steel yarn (SSf) was modified with a carbon ink to increase the fiber’s electrochemical activity.406 shows the modified SSf used as a working electrode, 408 shows apristine SSf used as a counter electrode, and 409 shows a silver fiber used as a reference electrode. The working, reference, and counter electrode form an electrochemical sensor and upon contact of fluid to a sensing zone (labeled as 407), a composition of the fluid can be analyzed. In some device embodiments, a portion of yarn (410) can protrude the layer or pad, and be utilized for coupling the sensor to an analyzer.

[0147] Now referring to the exemplary device 400 in FIG.44, the yam-based sensors (402) can be secured to a layer 408, and sandwiched between multiple layers (shown as 405, 406, 407) to create a layered pad that can sample and process the fluid released from mammary ducts. These layers 414905-3262-5274, v. 1may contain reagents for processing of fluid or for assisting in the analysis of fluid. In some device embodiments, a fluid inlet 404 can located above the sensing zone 403 to facilitate transfer of fluid to the sensing zone. In some device embodiments, a portion of yarn (402 in FIG.44A) can protrude the layer or pad, and be utilized for coupling the sensor to an analyzer.

[0148] Now referring to the exemplary device 400 in FIG. 45, yarn-based sensors can be incorporated in layers of the device without securing one or more than one yarn to a layer in the device through sewing or embroidery techniques. In some device embodiments, a portion of yarn (402 in FIG. 45 A) can protrude the layer or pad, and be utilized for coupling the sensor to an analyzer. FIG.45B shows the cross section of the exemplary device 400, where the yarn is in contact with any of the layers employed in the pad construction.

[0149] Referring now to an exemplary embodiment of the device 400 depicted in FIG. 46, a portion of the yarns protruding from the pad can be operatively coupled to an analyzer or an electrical connector via snap-on button assemblies. The yarns may be secured to either the conductive male or female portion of a snap-on button assembly, while the corresponding conductive counterpart (female or male) may be attached to the analyzer or electrical connector. When the male and female portions of the snap-on button assembly are engaged, an electrical connection is established between the yarns and the analyzer or electrical connector, facilitating the transfer of electrical signals or data. This configuration provides a reliable and detachable means for interfacing the yarns with external analytical or electrical systems.

[0150] In certain embodiments, a stainless-steel fiber (SSf) is employed as a flexible conductive element. Due to low intrinsic electrochemical activity of bare SSf, its surface is modi lied with conductive carbon-based inks doped with gold nanoparticles (AuNPs) to enhance electrocatalytic performance. The resulting carbon-AuNP-modified stainless-steel fiber (C-Au-SSf) provides improved electron transfer and high sensitivity for voltammetric detection of acetaminophen. Optimal performance is achieved using 20 pL AuNP solution per 3.5 g of carbon ink, yielding enhanced peak current response and reduced background capacitance. The C-Au-SSf exhibits linear correlation between peak current and acetaminophen concentration within 10-190 pM, with a limit of detection of 1.36 pM and limit of quantification of 4.54 pM. FIG. 47 illustrates rcprcscnlali vc voltammograms and calibration data demonstrating reproducible and stable electrode performance with relative standard deviation below 3%.

[0151] FIG. 47D shows square wave voltammograms (SWVs) of acetaminophen in un-diluted 6-month human milk, exhibiting a linear correlation between peak current and concentration from 9.9 to 218.7 pM (FIG. 47E). The calculated LOD and LOQ were 2.90 pM and 9.66 pM, respectively. The calibration established in 6-month milk was successfully applied to 1 -month 424905-3262-5274, v. 1and 12-month milk samples, yielding recovery values between 95% and 99%

[0013] , These results confirm that the C-Au-SSf enables accurate quantification of acetaminophen across diverse breast milk samples without requiring individual calibration. To assess reproducibility and repeatability, ten C-AuNP-SSf electrodes were tested in 6-month breast milk, yielding an RSD of 5.68% (FIG.47F), demonstrating consistent performance. Reproducibility may be further improved through automated fabrication rather than manual masking. To enable a fiilly integrated yam-based sensing platform, a three-electrode system was developed using a C-AuNP-SSf working electrode, a pristine SSf counter electrode, and an Ag-plated Nylon reference electrode. Calibration in 6-month milk produced clear SWVs (FIG. 47G) and a linear correlation between current and acetaminophen concentration (FIG. 47H). The same system accurately measured acetaminophen in 1 -month and 12-month milk samples (FIG. 471). Following validation of sensitivity and selectivity, a scalable and low-cost sensor array was fabricated via embroidery using a commercial embroidery machine, establishing a flexible, hilly yam-based sensing platform suitable for point-of-care and at-home applications.

[0152] A non-woven polypropylene textile (contact angle 85.7°) was rendered more hydrophobic (127.3°) using a biocompatible waterproofing spray (Scotchgard Fabric Water Shield) to prevent milk leakage and define the electrode’s active surface area. The treated fabric was mounted in an embroidery hoop with a water-soluble stabilizer and integrated into an embroidery machine. Electrodes were formed via lock-stitch embroidery, using stainless steel fiber (SSf) as the bottom bobbin thread and polyester as the top thread to minimize fluid wicking (FIG. 48). Optimized parameters included 2.5 mm stitch length and 35% tension for SSf, and 3.5 mm stitch length with 75% tension and double-pass stitching for Ag-plated yam to ensure conductivity and durability. After embroidery, a laser-cut mask defined the working electrode area for selective coating with C-AuNP ink. A hydrophilic gauze layer was stitched atop the sensing region to aid in milk sampling. When tested with human milk containing 166.4 pM acetaminophen, the embroidered sensor array produced accurate square -wave voltammograms, yielding recovery values of 96.2%, 107.1%, and 108.8%. These results confirm the feasibility of a fully embroidered, yarn-based electrochemical platform for acetaminophen detection in breast milk

[0013] ,EXAMPLE 4 - EMBODIMENTS of DEVICE SHAPE

[0153] Now referring to FIG. 49 and FIG. 50, the present invention contemplates various embodiments where a portion of a geometric shape, such as a circle, oval, or complex polygon, may be removed or modified to create a design that more effectively conforms to the anatomical contours434905-3262-5274, v. 1of the breast, thereby reducing mechanical tension during application. Specifically, FIG. 49 illustrates these embodiments: FIGS. 49 A and B show traditional full shapes, including circular (500) and elliptical (500) profiles. FIGS.49 C and D display modified profiles where an angular or concave section (501) has been removed from a circle or oval, forming notched or arcuate shapes (500) that facilitate improved conformance to the body’s contours. FIGS.49 E, F, and G depict more complex, multidobed shapes (500) with strategically placed recesses or indents (501), providing enhanced flexibility and mechanical compliance. These design modifications aim to address the mechanical stresses encountered when adhering conventional shapes to non-flat surfaces, promoting both comfort and stability through reduced structural tension.

[0154] Now referring to FIG. 50, the invention further contemplates that the afore-mentioned geometric shapes (500), as shown in FIG. 49, may incorporate a plurality of cutouts (502) extending through all layers of the device. These cutouts, which can be of any size, shape, and configuration, are strategically placed to enhance the coupling of the device with the underlying layer, which may be the body surface or an auxiliary component such as a lactation pad. FIG.50 A through G illustrate various embodiments of these shapes with cutouts (502) positioned to promote improved mechanical integration, stability, and adherence during use. The cutouts can be distributed symmetrically or asymmetrically across the shape, providing design flexibility that accommodates different functional requirements while maintaining structural integrity and comfort.EXAMPLE 5 - EMBODIMENTS of DEVICE COUPLING WITH A LACTATION PAD

[0155] In certain embodiments disclosed herein, at least one layer of the device may comprise an absorbing material, enabling the device to function as a conventional lactation pad while simultaneously performing sensing and / or fluid storage. However, it should be understood that, in other embodiments, the device may be configured without an absorbing material and can be adapted to couple with an existing lactation pad. In such embodiments, the device may be permanently affixed to a standard lactation pad or provided as a separate component that the user can attach to a lactation pad. Furthermore, in certain embodiments, the device may include an adhesive layer on one surface, which can be exposed by removing a protective strip, allowing the user to attach the device securely to a lactation pad. Referring now to FIG. 52, an exemplary embodiment of the device (600) configured to couple with a standard lactation pad (601) is depicted. FIG. 52A shows an embodiment where the device is secured to a lactation pad. FIG.444905-3262-5274, v. 152C the device is provided as a separate component that the user can attach to a lactation pad. In devices depicted in FIG. 52A-D, the device has at least one fluid inlet that is positioned near the mammary papilla to capture fluids released from mammary glands. In some embodiments, the device contains layers that sandwich a fluidic channel 603. This fluidic channel transports the fluid to a sensing zone 604. In certain device embodiments as depicted in FIG. 52D, the device may incorporate a plurality of cutouts (605) extending through all layers of the device. These cutouts, which can be of any size, shape, and configuration, are strategically placed to enhance the coupling of the device with a lactation pad. These cutouts may enhance the absorption of excess released fluid by the lactation pad, and / or increase dry feeling against skin, and / or increase the comfort of the subject wearing the device.

[0156] Now referring to FIG. 53 and FIG. 51, the depicted exemplary device 600 includes a water-impermeable first layer 605, a cutout in the first layer (labeled as 611) that exposes a fluidic inlet 602 that is fluidically connected to a fluidic channel 603, a sensor 604 positioned adjacent to the fluidic channel 603, and a last water-impermeable layer 610. The exemplary device 600 can couple with a lactation pad 601. In certain device embodiments, the last layer 610 may contain may include an adhesive layer on one surface, which can be exposed by removing a protective strip, allowing the user to attach the device securely to a lactation pad. In certain device embodiments, the last layer 610 may incorporate a plurality of cutouts (labeled as 608) that do not extend to all the device layers. These cutouts (example of such shown as 609 in FIG.53B) may be strategically positioned to expose a portion of the fluidic layers (example of such shown as 608 in FIG. 53B) at one end of the device, allowing for fluidic connection between the device and a lactation pad when device is coupled with the lactation pad. In such embodiments, the lactation pad may absorb the fluids in the fluidic channel and act as a fluidic pump, continuously removing fluid from the fluidic channel and allowing the channel to be filled with new fluid as it gets leaked from the mammary papilla and / or mammary ducts.

[0157] Now referring to FIG. 54, the depicted exemplary device 600 includes a water-impermeable first layer 605 , a fluidic inlet 602 that is fluidically connected to a fluidic channel 603 , a sensor 604 positioned adjacent to the fluidic channel 603, and a last water-impermeable layer 610. The exemplary device 600 can couple with a lactation pad 601. A portion of the fluidic channel 603 may protrude from the layer 610, and remain exposed at one of the device. When the device exemplary device 600 is coupled with a lactation pad 601 , the portion of the fluidic channel that protrudes the water-impermeable layer can make fluidic contact with the lactation pad. In such embodiments, the lactation pad may absorb the fluids in the fluidic channel and act as a fluidic pump, continuously removing fluid from the fluidic channel and allowing the channel to be filled 454905-3262-5274, v. 1with new fluid as it gets leaked from the mammary papilla and / or mammary ducts.

[0158] Referring now to FIG. 55, an exemplary embodiment of the device 600 is shown, comprising a water-impermeable first layer 605 with a cutout 611 that exposes a fluidic inlet 602 fluidically connected to a fluidic channel 603, a sensor 604 positioned adjacent to the fluidic channel 603, and a last water-impermeable layer 610. The device 600 is configured to couple with a lactation pad 601. In certain embodiments, the fluidic channels may include at least one valve configured to regulate, direct, or restrict the flow of fluid within the channels. The valve may be selected from, but is not limited to, the group consisting of mechanical, pneumatic, thermally-actuated, electrochemical, or elastomeric valves. Such valves may be utilized to assist with fluid storage, sensing a composition of a fluid, or controlling the timing of a reaction, among other functions.

[0159] Referring now to FIG. 56, an exemplary embodiment of device 600 is shown coupled to a lactation pad 601. A fluidic inlet 602 is in fluidic communication with a fluidic channel 603 configured to direct the flow of biofluid toward a sensing region 604. In certain embodiments, the sensing region 604 comprises one or more colorimetric reagents configured to undergo a visually or optically detectable color change in response to the presence or concentration of at least one biomarker within the biofluid. The extent or intensity of the color change may be proportional to the biomarker concentration, thereby enabling qualitative, semi-quantitative, or quantitative assessment of analyte levels. FIG. 57 demonstrates examples of such colorimetric reagents, selective for measurement of glucose, zinc, alcohol, and choline — biomarkers of interest for breast milk analysis.

[0160] In certain embodiments, colorimetric reagents were prepared in aqueous buffer systems and immobilized on 4 mm diameter filter-paper disks, followed by drying at 37 °C for 20 min. A zinc assay was prepared using 1 mM 5-bromopyrogallol-O-sulfonic acid (5-Br-PAPs) in deionized water. A glucose assay mixture included glucose oxidase, horseradish peroxidase, trehalose, and potassium iodide in sodium citrate buffer (pH 6.0). An alcohol assay reagent contained alcohol oxidase, horseradish peroxidase, and a chromogenic mixture of 3,5-dihydroxybenzenesulfonic acid and 4-aminoantipyrine in phosphate-buffered saline (pH 7.4). A choline assay reagent included choline oxidase, horseradish peroxidase, and citrate buffer (pH 6.0), with optional activation by 10 mg / mL ethanol in an ethanol / dimethyl sulfoxide (9:1 v / v) solution. All reagents were homogenized before application and stored dry and light-protected until use.

[0161] Referring now to FIG. 58, an exemplary device 600 configured for coupling with a lactation pad 601 is illustrated. The device 600 is provided as a separate component that can be removably attached to a lactation pad. In the depicted embodiment, the device 600 includes 464905-3262-5274, v. 1at least one fluid inlet 602 and at least one fluidic channel 603 configured to transport fluid to a sensing region. In certain embodiments, the device 600 further comprises a removable strip 615 configured to expose an adhesive layer to facilitate attachment of the device to the lactation pad. In additional embodiments, the device 600 may include an analyzer 616 adapted to receive one or more sensors for performing operations including, but not limited to, power transfer, data acquisition, signal analysis, and other related functions.EXAMPLE 6 - DIAGNOSIS OF MASTITIS

[0162] Mastitis, inflammation of breast tissue caused by blocked milk ducts, affects approximately 33% of lactating mothers. The initial stage of this condition, known as subclinical mastitis, often goes undiagnosed due to its asymptomatic presentation. Previous research has indicated that the sodium-to-potassium ratio (Na K+) increases during subclinical mastitis, positioning this ratio as a potential diagnostic biomarker. In this study, we used LIG-based potentiometric sensors for sodium (Nc ) and potassium (K+), integrated with an ionic liquidbased reference electrode, facilitating the early detection of mastitis. Early detection enables mothers to implement preventative measures before progression to clinically evident mastitis. The device of FIG. 58 is configured for measuring Na+and K+in mammary gland fluid for mastitis diagnosis and monitoring. LIG electrodes are modified with ion-selective membranes incorporating valinomycin for K+and sodium ionophore X for Na+. The sensors exhibit Nernstian responses with slopes of approximately 58-60 mV / decade (FIG. 59)

[0038] , An ionic liquid-based reference electrode and a wicking material are integrated without affecting sensor performance. The device provides accurate measurements in healthy and mastitis-affected milk, comparable to commercial benchtop sensors, confirming its suitability for wearable applications (FIG. 60).EXAMPLE 7 - ANALYSIS OF LITHIUM IN BREAST MILK

[0163] The device of FIG. 58 is configured for the detection of Ei+in breast milk. Lithium, a pharmacological agent for mood stabilization, is transferred into breast milk via active transport, passive diffusion, or apocrine secretion, reaching peak concentrations approximately 2M- hours post-administration. Neonatal exposure poses risks due to immature renal function, including cyanosis, hypotonia, hypothermia, and cardiac complications. The device provides alow-cost, user-friendly platform for real-time lithium monitoring, enabling safer management of maternal lithium therapy and reducing neonatal toxicity risk. In the device of FIG.58, the laser-induced graphene474905-3262-5274, v. 1(LIG) electrodes are modified with a Li+-selective membrane comprising a Li+ionophore. The electrodes exhibit near-Nernstian behavior, with a measured sensitivity of 58.08+0.5 mV / dec and a detection limit of 5.06 pM in aqueous solution. In the presence of vitamins commonly found in breast milk, the electrodes maintain Nemstian response (54.36+1.58 mV / dec) and a detection limit of 28 pM. Using a Li+electrode coupled with a glass fiber wicking layer, the device was validated in pooled breast milk samples spiked with lithium, demonstrating a measurement error below 20% . The platform provides real-time quantitative feedback to support therapeutic management and minimize risk to both mother and infant.EXAMPLE 8-Other Device Embodiments

[0166] Now referring to FIG. 62, FIG. 63, FIG. 64, FIG. 65, FIG. 66, and FIG. 67, in certain device embodiments, an exemplary device 700 may include a hollow structure 706 configured to accommodate the mammary papilla. The hollow structure 706 may facilitate sensitive-skin protection, biofluid sampling, targeted fluid routing, or any other fiinctional requirement of the device. In such embodiments, the device may include a skin-contacting layer 704, and in some embodiments at least one additional layer 716 designed to enhance comfort, breathability, mechanical compliance, moisture management, and / or secure attachment to the skin. In some embodiments, the device may include one or more openings that provide a fluidic connection between the skin-contacting region and a fluidic layer 710. The fluidic layer 710 may collect, wick, or transport biofluid — such as breast milk, interstitial fluid, sweat, or any combination thereof — Io at least one sensor 712 for chemical, biochemical, electrochemical, optical, or mechanical analysis. In certain embodiments, the device may fiirther include a processor 714 that is electrically and / or fluidically coupled to the sensor 712. The processor 714 may perform any of the following functions: signal processing; analog or digital filtering; amplification; application of current or voltage waveforms; wireless or wired power transfer; wireless or wired data communication; on-device computation; local data storage; sensor calibration; temperature compensation; timing control; or activation of valves, pumps, or dissolvable membranes. In some embodiments, the device may include one or more barrier layers 718 configured to enhance mechanical integrity, provide insulation or dielectric barriers, protect internal components, increase robustness against bending or compression, or otherwise support the structural or functional operation of the device. As depicted in FIG. 65, the processor 714 may include coils, antennas, or other electronic structures enabling wireless communication (e.g., RFID, NFC, Bluetooth), inductive power transfer, resonant sensing, or additional electronic functionalities. In484905-3262-5274, v. 1certain embodiments, the device may additionally include at least one colorimetric sensing region 712 fluidically connected to the fluidic layer 710. Such sensing regions may contain reagents that undergo a visible color change proportional to the concentration of a biomarker in the collected biofluid. In some embodiments, the device may include a color indicator chart 720 positioned on the device surface to enable quantitative or semi-quantitative biomarker analysis by visual comparison or by digital imaging via a smartphone or external reader.

[0167] Now referring to FIG. 63, in certain device embodiments, the device may include one or more fluidic processing layers 722. The fluidic processing layer 722 may perform any combination of the following fiinctions: storing reagents for sensing, sample stabilization, enzymatic reaction, labeling, or chemical processing; filtering or pre-treating the biofluid; mixing reagents with the biofluid; regulating or modifying fluid flow; incorporating valves — including mechanical, dissolvable, pressure-activated, or thermally activated valves — Io control assay timing; and enabling sequential or multiplexed testing. The fluidic processing layer 722 may have any suitable shape, thickness, or layout and may overlap spatially with the fluidic layer 710. Referring to the device embodiment shown in FIG. 63B, additional fluidic layers 711 and valves 713 may be incorporated to further direct, process, meter, or route biofluid through the device. In certain embodiments, the skin-contacting layer 704 and / or the barrier layer 718 may contain openings that allow fluid to exit or enter the device to support active infant feeding, improve airflow, enhance comfort or breathability, or accomplish any other desired function.

[0168] Referring to the embodiment in FIG. 64, the barrier layer 718 may include one or more openings that permit controlled fluid release or transfer, facilitate user comfort, or enable active breastfeeding while the device remains in place. As shown in FIG. 66, the fluidic layers and sensors may be located at any position relative to the skin-contacting layer 704 and the hollow structure 706. In some embodiments, the device may include a removable strip 724 located at any suitable region of the device. Removal of the strip 724 may expose an adhesive layer designed for attachment to skin, a garment, or another supporting structure. In certain embodiments, the device may include one or more regions configured to store or preserve biofluid for later analysis, archival, or shipment to a processing center. Such embodiments may serve as integrated drysample collection cards (e.g., dry milk cards). The device may fiirther include perforated or detachable sections that can be removed and sent for remote laboratory testing or confirmatory diagnostics.

[0169] Referring now to FIG. 67, the fluidic layer 710 may be introduced through hollow channels or structural conduits within the device rather than by the addition of new or separate material. In these embodiments, the sensor 712 and processor 714 may be positioned adjacent 494905-3262-5274, v. 1to or in direct contact with such channels to ensure reliable fluidic communication. As in other embodiments, the skin-contacting layer 704 and / or the barrier layer 718 may include openings that allow fluid transport outward from the device to enable infant feeding, increase comfort or breathability, or support other functional requirements.

[0170] FIG. 68 depicts a system diagram 800. System diagram 800 includes a mammary gland 805. Mamary gland 805 produces a biofluid 810. Biofluid 810 may, for example, include milk. Bio Fluid 810 is collected via a lactation cover device 815. The lactation cover device 815 may, for example, include exemplary device 100. Exemplary device 100 may, for example, include a lactation pad. The lactation pad may, for example, be referred to as a cover and be used interchangeably. The lactation pad may, for example, include a cover fluidly coupled to a receptacle to store breast milk. The lactation cover 815 may, for example, include other lactation pad discussed herein. The lactation cover 815 includes a sensor. The lactation cover device may, for example, include a receptacle. The lactation cover device 815 is communicable coupled to an input / output module 825. The input / output module is included in a smart device 820. Smart device may, for example, include a smart phone, computer, and / or other electronic devices. The input / output module 825 is communicatively coupled to a processor 830. The processor 830 is communicatively coupled to a memory 835. Memory 835 stores an analysis engine 840 that may, for example, include a software used to analyze the milk as described in a method 900. The input / output module 825 is communicatively coupled to a cloud database 855. The input / output module 825 is commutatively coupled to a database 850. The input / output module 825 is communicatively coupled to a large learning model (LLM) 845. The large learning model may, for example, include a machine learning model. The large learning model may, for example, include applications of artificial intelligence used to analyze or be used as a supplement to analyze the breast milk.

[0171] FIG. 9 depicts the method 900. Method 900 begins with step 905, wherein a user of the method places a device on the body of a subject. For example, the lactation cover or lactation pad may, for example, be placed on a patient’s breast. In step 910, the lactation pad or cover may, for example, measure the concentration of a drug or drug metabolite. In step 915, the lactation pad may, for example, collect data and communicate it to a processor to monitor pharmacometrics of a drug (e.g., absorption, distribution, metabolism, and excretion).

[0172] In step 920, the user of the method calculates the milk to plasma ratio. This method may, for example, be implemented by a computer processor coupled to a memory configured to complete operations to evaluate the milk.

[0173] In step 925, the user of the method (e.g., a computer processor, a user using a smart 504905-3262-5274, v. 1device) may, for example, determine whether the concentration is within a therapeutic range. If the concentration requires adjustment, in step 930 the user of the method adjusts the does. In step 935, the user of the method determines whether it passes pharmaceutical evaluation. In step 940, the user of the method determines whether it passes safety evaluations. In step 945, the user of the method determines whether it passes health evaluations. The does may, for example, be adjusted if the concentration is not within the Ihcrapculic range, did not pass the pharmaceutical evaluation, did not pass the safety evaluation, or did not pass the health evaluations.

[0174] It will thus be seen that the objects set forth above, among those made apparent from the preceding description, are efficiently attained and, because certain changes may be made in carrying out the above method and in the construction(s) set forth without departing from the spirit and scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

[0175] FIG. 70 depicts an exemplary system 1000 diagram of a dry milk card, or sample collection for off-site analysis. System 1000 includes a patient that has a mammary gland 805. Mamary gland 805 produces biofluid 810. Biofluid may, for example, include breast milk. Biofluid 810 is collected from a lactation cover device 815. Lactation cover device 815 includes a milk card 1010. The milk card may, for example, include an absorbing layer to collect milk samples. The milk card may, for example, be sent off site to be examined. The milk card may, for example, be frozen and shipped to a collection system 1015. Collection system 1015 includes a sensor 1020 coupled to a processor 830 to analyze the milk and communicate it to a collection system 1010. The collection system 1015 may, for example, use an analysis engine 840 to evaluate the milk sample in the milk card 1010. The collection system 1015 may, for example, communicate to cloud database 855. The collection system may, for example, communicate to database 850. The collection system may, for example, communicate to LLM 845.

[0176] It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described and all statements of the scope of the invention which, as a matter of language, might be said to fall there between.514905-3262-5274, v. 1REFERENCESThe following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.US 7, 132, 660 B2US11235093B1US11097039B2US10639407B2US12115294B2US10046097B2US20200155738A1KR101622768B1ES2949271T3USD936823S1USD969305S1US20200404984A1US11304457B2[1] Journal of Pediatric and Neonatal Individualized Medicine (JPNIM), 1, 11-18.[2] Journal of Mind and Medical Sciences, 5, 151-157. 1[3] Pediatric Clinics, 60, 31^4-8. 1[4] Frontiers in nutrition, 7, 54. 2[5] The American journal of clinical nutrition, 99, 734S-741S. 2[6] W. H. Organization, et al., Mastitis: causes and management, Technical report, World Health Organization, 2000. 2[7] Journal of Human Lactation, 30, 10-13. 2[8] American journal of epidemiology, 155, 103-114. 2[9] American Journal of Obstetrics and Gynecology, 108, 78-81. 2

[0010] Pediatrics, 93, 802-806. 2

[0011] Annals of Pharmacotherapy, 37, 1299-1306. 3, 55, 56

[0012] Clinical obstetrics and gynecology, 58, 868-884. 3

[0013] Npj Women’s Health, 3, 48. 3, 63, 64

[0014] Fda-permits-marketing-diagnostic-test-aid-measuring-nutrients-breast-milk,

[0015] Current Developments in Nutrition, 3, nzzl 16. 4524905-3262-5274, v. 1

[0016] Lactationlab, 4

[0017] Milkify, Nutritional analysis, 4

[0018] Pediatrics, 101, e2-e2. 4

[0019] Pediatric Research, 95, 819-826. 4

[0020] UpSpring, Milkscreen,

[0021] Frida, Breastmilk Alcohol Detection Test Strips

[0022] Journal of Nurse-Midwifery, 34, 15-20. 5

[0023] Advanced Functional Materials, 2420973. 48 , 49 , 51 , 52, 54

[0024] Journal of the national medical association, 97, 1010. 48

[0025] Pediatric Clinics, 66, 333-342. 48, 49

[0026] Nutrients, 13, 3724. 48

[0027] Food and Nutrition Sciences, 2011. 48

[0028] Journal of Human Nutrition and Dietetics, 22, 166-169. 48

[0029] Indian Pediatr. 49

[0030] ACOG Clinical Consensus. 55

[0031] J. Pediatr. Pharmacol. Ther., 28, 20. 55

[0032] A. C. Bronstein, D. A. Spyker, L. R. Cantilena Jr, B. H. Rumack, R. C. Dart, 2011 annual report of the american association of poison control centers’ national poison data system (npds): 29th annual report, 2012. 55

[0033] T. W. Hale, Medications and Mothers’ Milk, Springer, New York, 17th edition, 2017. 55

[0034] U. N. L. of Medicine, LactMed: Drugs and Lactation Database, 2024. 55

[0035] Pediatric Pharmacology (New York, NY), 1, 135-141. 55

[0036] Pediatrics, 127. 56

[0037] Device. 57

[0038] Advanced f unctional Materials, 35, 2313707. 70534905-3262-5274, v. 1

Claims

What is claimed is:

1. A device comprising :a pad comprising a first side, a second side and one or more fluidic channels, wherein: the first side of the pad is configured to be worn against a mammary gland of a user; and the one or more fluidic channels are configured to collect a biofluid from the mammary gland, and / or mammary ducts, and / or mammary papilla of the user.

2. The device of claim 1, wherein the device is configured to analyze a composition of the biofluid.

3. The device of any one of claims 1 to 2, wherein the biofluid is human milk.

4. The device of any one of the claims 1 to 3, wherein the one or more fluidic channels extend from the first side of the pad to the second side of the pad.

5. The device of claim 4, wherein the second side of the pad comprises a hydrophobic and / or water impermeable and / or water resistant material.

6. The device of claim 5, wherein the second side of the pad contains an adhesive.

7. The device of claims 1 to 5 where the device contains at least one fluidic channel layer, one water-permeable layer, one water-impermeable layer, and an optional fluidic processing layer.

8. The device of claims 1 to 7 where the device couples with a lactation pad and / or a absorbing material.

9. The device of claims 7, wherein the fluid processing layer any of filtration, separation, mixing one or more reagents, transferring to one or more sensors, or any combination thereof.

10. The device of any one of claims 1 to 9, wherein the one or more fluidic channels are hydrophilic.

11. The device of any one of claims 1 to 10, wherein the one or more fluidic channels comprise a hydrophobic edge at the first side of the pad.544905-3262-5274, v.

112. The device of claim 1 to 11, wherein the absorbent material comprises natural materials or polymeric materials.

13. The device of claim 12, wherein the natural materials are selected from cotton, linen, silk, wool, hemp, ramie, bamboo, cellulose-based materials, or any combination thereof.

14. The device of claim 12, wherein the polymeric materials are selected from poly-acrylate, sodium polyacrylate, a super-absorbing polymer, polyamide, polyethylene, polypropylene, polyester, polyoxymethylene, polyvinyl alcohol, polycarbonates, silicones, fluoropolymers, polyketones, polyacrylic, polystyrenes, poly-lactic acid, poly(lactic-co- glycolic) acid, polyurethane, polyetheretherketone (PEEK), polyimide, polyethylene terephthalate (PET), polyvinyl chloride (PVC), chitosan, thermoplastic elastomers (TPE), polycaprolactone (PCL), polyphenylene sulfide (PPS), acrylic (PMMA), and nylon.

15. The device of any one of claims 1 to 14, wherein the device further comprises atleastone wicking element and / or fluid processing layer, wherein the at least one wicking element and / or one fluid processing layer is in fluid communication with the one or more fluidic channels.

16. The device of claims 15, wherein the at least one wicking element and / or fluid processing layer comprises a paper, glass fiber, nitrocellulose, textile, or any combination thereof.

17. The device of claims 15 or 16, wherein the at least one wicking element exhibits a capillary wicking.

18. The device of any one of claims 15 to 17, wherein the at least one wicking element is configured to allow for continuous flow of the biofluid.

19. The device of any one of claims 15 to 17, wherein the at least one wicking element comprises a terminal end that allow for continuous flow of the biofluid.

20. The device of any one of claims 15 to 19, wherein the at least one wicking element comprises a terminal end that is connected to an absorbing material.

21. The device of any one of claims 15 to 20, wherein the at least one wicking element comprises one or more agents.554905-3262-5274, v.

122. The device of claim 21 , wherein the one or more agents comprise a surfactant, a stabilizer, a pH buffer, a pharmacologically active agent, a reagent configured to assist in a sensing reaction and / or biomarker stabi lizalion, fluid transport, or any combi nalion thereof.

23. The device of any one of claim 15 to 22, wherein the at least one wicking element is optional I y independently removable from the device.

24. The device of any one of claim 1 to 23, further comprising a sensory portion comprising one or more sensors, wherein the sensory portion is in fluid communication with the one or more fluidic channels.

25. The device of claims 24, wherein the one or more sensors comprise a yarn or fiber.

26. The device of claims 24, wherein the sensory portion is in fluid communication with the at least one wicking element.

27. The device of any one of claims 24 to 26, wherein the one or more sensors comprise an optical sensor, a lateral flow assay, a colorimetric assay, an electrochemical sensor, a capacitive sensor, a thermal sensor, a magnetic sensor, a surface-enhanced Raman scattering (SERS) -based sensor, or sensor based on electrochemiluminescence (also known as electrogenerated chemiluminescence or ECL), or any combination thereof.

28. The device of claim 27 , where the electrochemical sensor comprises one or more electrodes , wherein at least one electrode is a reference electrode and at least one electrode is a working electrode.

29. The device of claim 28, where the electrochemical sensor comprises of more electrodes, where at least one electrode is a counter or auxiliary electrode.

30. The device of claim 28, where the electrochemical sensor contains more than one working electrode.

31. The device of claims 24 to 30, wherein the one or more sensors comprise a conductive material and / or a semiconductive material.

32. The device of claims 5 to 24, wherein at least one sensor is flexible and / or stretchable.564905-3262-5274, v.

133. The device of claims 28 to 32, wherein at least a portion of a surface of one or more electrodes is modified with a reagent.

34. The device of claims 33, wherein one or more reagents comprise one or more of an organic molecule, an antibody, nucleic acid, aptamer, enzyme, nanobody, peptide, a protein, ahydrogel, apolymer, a nanoparticle, ametal organic frame-work (MOF), covalent-organic frameworks (COF), a biological and / or an organic biorecognition element, an ion-sensing membrane, or a plurality of nano and microparticles or any combination thereof.

35. The device of any one of claims 24 to 34, wherein the one or more sensors are configured to detect a level of an ion, an organic molecule, a protein, a metabolite, a drug, an antibody, a hormone, and a nucleic acid in the biofluid.

36. The device of any one of claims 1 to 35, wherein the device contains a processing unit.

37. The device of claim 36 where the processing unit is an electronic element.

38. The device of claim 37 , wherein the electronic element comprises an electronic processor.

39. The device of any one of claims 1 to 37, wherein at least a portion of the device is disposable.

40. The device of any one of claims 1 to 39, wherein at least a portion of the device is reusable.

41. The device of any one of claims 1 to 40, wherein the device is electronically connected to a processing unit configured to evaluate and / or indicate a characteristic of at least one property of the biofluid.

42. The device of claim 41, wherein the processing unit comprises a plurality of receiver channels, each processing channel comprising a sensor.

43. The device of claims 41 or 42, wherein the processing unit is directly coupled with the device, or it is a separate unit.

44. The device of any one of claims 41 to 43, wherein the processing unit is in a wireless or wired communication with the device.

45. The device of any one of claims 41 to 44, wherein the processing unit is a detector, a potentiostat, a potentiometer, or a combination thereof.574905-3262-5274, v.

146. The device of any one of claims 41 to 45, wherein the processing unit may contain a flexible circuit.

47. The device of claim 46, wherein the flexible circuit is removable.

48. The device of any one of claims 41 to 46, wherein the sensors may connect to each other and / or to the circuit via snap-on-buttons.

49. The device of any one of claims 41 to 48, wherein the device is electrically connected to the processing unit via a yarn.

50. The device of any one of claims 1 to 49, wherein the device is in wireless communication with a handheld device con figured to provide a data analysis to a user.

51. The device of claim 50, wherein the handheld device is a phone, a ring, a tablet, a computer, a watch, or any combination thereof.

52. The device of any one of claims 1 to 51 , wherein the device is insertable and / or attachable to an article of clothing.

53. The device of any one of claims 1 to 51, wherein the device is reversibly insertable and / or attachable to an article of clothing.

54. The device of any one of claims 1 to 51, wherein the device is an article of clothing.

55. The device of claim 54, wherein the article of clothing is a bra.

56. The device of any one of claims 1 to 55 , wherein the device further comprises a receptacle in fluid communication with the one or more fluidic channels.

57. The device of any one of claims 56, wherein the receptacle comprises an ab-sorbent material.

58. The device of any one of claims 56 to 57 , wherein the receptacle is a detachable receptacle.

59. The device of claim 58, wherein the detachable receptacle comprises a plurality of colorimetric assays, each configured to detect a distinct biomarker.584905-3262-5274, v.

160. The device of any one of claims 56 to 59, wherein the detachable receptacle can be removed from the body and be placed in a separate device.

61. The device of claim 60, wherein the separate device processes the fluid via any of heating, sonication, rotation, cenlrilugalion, vibration, dispensing reagents, applying energy in form of sound, ultrasound, light, radiation, magnetic, volt-age, and / or measures a property of the fluid via microscopy and imaging, and / or performing analysis, data storage, and / or data visualization.

62. The device of any one of claims 56 to 59, wherein the biofluid is transferred to the receptacle and undergoes a processing step.

63. The device of any one of claims 56 to 62, wherein the receptacle further com-prises an electronic element.

64. The device of any one of claims 56 to 63, wherein the receptacle comprises one or more sensors for at least one biomarker.

65. The device of any one of claims 56 to 64, wherein at least one wicking element is disposed within the receptacle, and wherein the at least one wicking element is optionally independently removable from the device.

66. The device of any one of claims 56 to 65, wherein the receptacle comprises a sensory portion comprising one or more sensors, wherein the sensory portion is in fluid communication with the one or more fluidic channels.

67. The device of any one of claims 1 to 66, wherein the pad is configured to couple to a lactation pad.

68. The device of any one of claims 24 to 67, wherein the sensors are configured to perform analysis based on either a distance traveled by the biofluid within the one or more fluidic channels or a length of color developed in the one or more fluidic channels, and wherein the device comprises corresponding markings to facilitate quantitative assessment.

69. The device of any one of claims 1 to 68, wherein the one or more fluidic channels comprise markings configured for the quantification of fluid flow or reaction results, and wherein the markings are configured to enable measurement based on the distance traveled by the594905-3262-5274, v. 1fluid or the length of a color change formed within the channel, thereby facilitating quantitative and / or semi-quantitati ve assessments.

70. The device of any one of claims 1 to 69, wherein the one or more fluidic channels comprise at least one valve configured to regulate, direct, or restrict the flow of the biofluid within the channels.

71. The device of 70, wherein the at least one valve is a mechanical valve, pneumatic valve, thermally-actuated valve, electrochemical valve, or elastomeric valve.

72. The device of any one of claims 1 to 71, wherein the device can be in fluidic communication with a lactation pad through an open microfluidic channel and wherein the lactation pad can facilitate fluidic transfer in the device.

73. The device of any one of claims 1 to 72, wherein a portion of the device contains an Radio Frequency Identification (RFID) component configured for one or more of the following functions: tracking the usage of the device, identifying the device, monitoring environmental conditions, storing data related to fluid analysis, facilitating wireless communication of data to external devices, enabling authentication and security features, or assisting in inventory management.

74. The device of any one of claims 1 to 73 wherein the device further comprises an integral analyzer.

75. A method of manufacturing the device of any one of claims 1 to 74, wherein the pad is manufactured by altering a lactation pad.

76. A method of using the device of any one of claims 24 to 74, comprising the steps of placing the device on the body of a subject, wherein the sensors measure a concentration of a drug or drug metabolite in the biofluid over time.

77. The method of claim 76 farther comprising analyzing collected data to monitor pharmacokinetics of the drug, including absorption, distribution, metabolism, and / or excretion.

78. The method of any one of claims 69 to 77, wherein the sensors monitor the concentration of the drug in the biofluid to determine whether the concentration is within a therapeutic604905-3262-5274, v. 1range, and adjusting the drug dosage based on the concentration to maintain or modify therapeutic efficacy.

79. A method of using the device of any one of claims 24 to 74, comprising the steps of measuring a concentration of a drug or drug metabolite in breast milk and simultaneously or sequentially measuring the concentration in plasma, to calculate the milk-to-plasma ratio of the drug and assess drug transfer to breast milk for pharmacological and / or safety evaluations and / or health evaluations.

80. A method of using the device of any one of claims 24 to 74 for diagnosis of mastitis.

81. A kit comprises a plurality of the devices of any one of claims 1 to 74.

82. The kit of claim 81, wherein the kit further comprises one or more active reagents provided separately from the device or within the device.

83. The kit of claim 81 or 82, further comprising a container configured to receive the device comprising a collected biofluid of a user.

84. The kit of claim 83, wherein the container is configured to be delivered for analysis.

85. The kit of claim 83, wherein the container is a biohazard container.

86. The kit of any one of claims 81 to 85, wherein the kit comprises a user manual.

87. The kit of any one of claims 81 to 86, wherein a portion of the kit comprises an Radio Frequency Identification (RFID) component configured for one or more of the following functions: tracking the usage of the device, identifying the device, monitoring environmental conditions, storing data related to fluid analysis, facilitating wireless communication of data to external devices, enabling authentication and security features, or assisting in inventory management.

88. The kit of any one of claims 81 to 86, wherein the kit is configured to detect mastitis, wherein the one or more sensors of the pad are configured to detect a relative level of sodium, potassium, and / or a ratio of sodium to potassium in the biofluid.

89. A kit comprising a device of any one of claims 1 to 73 and an article of clothing.

90. The kit of claim 89 wherein the article of clothing contains the device.614905-3262-5274, v.

191. The kit of any one of claims 89 to 90, wherein the article of clothing is a bra.

92. The device of claim 50, wherein the handheld device is able to perform a variety of artificial intelligence and machine learning algorithms, including but not limited to image segmentation and classification.

93. The device of claims 50 and 92, wherein the artificial intelligence and machine learning algorithms are run locally or over cloud.

94. A method of manufacture of the device of any one of claims 1 to 55 , the method comprising:disposing the receptacle on a first layer; forming one or more fluidic channels through the first layer and the receptacle.

95. The method of manufacture of claims 89, the method further comprising dis-posing the at least one wicking element and a sensor on the second side of the receptacle, wherein the at least one wicking element is in fluidic communication with the one or more fluidic channels, wherein the sensor is in fluidic communication with the wicking element.

96. The method of manufacture of claim 90, the method further comprising fabrication of the sensor.

97. The method of manufacture of claim 96, wherein fabricating the sensor comprises:providing graphene on to a polyimide polymeric sheets (PI), wherein providing includes laser engraving method.

98. The method of manufacture of claim 97 , wherein l abrical i ng the sensor furl her comprises :drop casting Ag and / or AgCl ink; sealing the metal electrode and counter electrode; electrodepositing a semi -conductive layer; and drop casting an enzymatic membrane.

99. A method comprising positioning the device of any one of claims 1 to 55, to a breast of a user during a period of lactation; collecting human milk in the device of any one of claims 1 to 55.

100. The method of claim 99, the method further comprising detecting at least one biomarker.

101. The method of claim 100, the method further comprising reading a result on the device.624905-3262-5274, v. 1102. The method of claim 100, wherein the detecring takes place in a processing unit, and wherein the processing unit is external to the device.

103. The method of any one of claims 99 to 102, wherein detecting at least one biomarker and / or medicinal is carried out continually over several hours.

104. The method of any one of claims 99 to 102, wherein detecting at least one biomarker and / or medicinal is carried out over several minutes.

105. The method of claim 99, the method further comprising removing the device from the breast and drying the device.

106. The method of claim 99, the method further comprising removing the device from the breast of a user and placing it in separate device for processing.

107. The method of claim 106, wherein the processing comprises heating, sonication, rotation, and / or centrifugation.

108. A system comprising a device of any one of claims 1 to 55 and at least one processing unit.

109. A system comprising: a computing device operably coupled to the device of any one of claims 1 to 55 , wherein the computing device comprises at least one processor and memory, the memory having computer-executable instructions stored thereon that, when executed by the at least one processor, cause the at least one processor to: perform the method of any one of claims 99 to 105.

110. The method of any one of claims 99 to 103, wherein detecting at least one biomarker may carried out using artificial intelligence and machine learning models, including but not limited to image segmentation and classification.

111. A device comprising :a pad comprising a plurality of layers, wherein the pad is configured to be worn against a mammary gland of a user; anda channel, wherein the channel is configured to collect a biofluid secreted from the mammary gland of the user.634905-3262-5274, v. 1112. The device of claim 111 wherein the pad is configured to form a concave shape when placed against a mammary gland of the user.

113. The device of any one of claims 111 to 112, wherein the pad comprises a generally circular shape.

114. The device of any one of claims 111 to 112, wherein the pad may be a geometric shape such as a circle, oval, or complex polygon.

115. The device of any one of claims 111 to 115, where a portion of a geometric shape, such as a circle, oval, or complex polygon, may be removed or modi lied to create a design that more e ffect i vely conforms to the anatomical contours of the breast.

116. The device of any one of claims 111 to 115 wherein the pad comprises one or a plurality of cutouts that extend partially or completely extends through all layers of the device.

117. The device of any one of claims 111 to 116 further comprising a sensor configured to analyze the biofluid secreted from the mammary gland of the user.

118. The device of any one of claims 111 to 117 wherein the sensor is configured to detect one or more of: an ion, an organic molecule, a medication or drug, a nucleic acid , an antibody, a protein, an antigen, a bacteria, a virus, a parasite, a fungus, a mineral, a vitamin, a lipid, and a hormone.

119. The device of any one of claims 117 to 118 wherein the sensor is configured to measure a composition of the biofluid secreted from the mammary gland of the user.

120. The device of any one of claims 117 to 119 wherein: the channel is a first channel in a plurality of channels; and the plurality of channels are configured to provide a fluidic coupling between the mammary gland of the user and the sensor.

121. The device of any one of claims 111 to 120 wherein:the plurality of layers comprises a first layer, a second layer and a third layer; and the channel traverses the first layer, the second layer and the third layer.

122. The device of claim 121 wherein cutouts may be made in each layer to manipulate fluidic connection of layers in the device.644905-3262-5274, v. 1123. The device of claim 121 wherein:the first layer is a fluid permeable layer; and the third layer is a fluid impermeable layer.

124. The device of claim 123 wherein:the second layer is an absorbent layer.

125. The device of claim 123 wherein the second layer may include adhesives to facilitate attachment to the article of clothing.

126. The device of claim 123 wherein the second layer may include a removable strip at the back that exposes the adhesive.

127. The device of any one of claims 111 to 124 wherein:the pad comprises a fluid inlet con figured to direct the biofluid secreted from the mammary gland of the user to the channel.

128. The device of claim 127 further comprising: a fluidic barrier surrounding the fluid inlet.

129. The device of claim 128 wherein the fluidic barrier is generally circular in shape.

130. A device comprising:a hollow structure configured to accommodate the mammary papilla;at least one skin-contacting layer; and,one or more openings that provide a fluidic connection be-tween the skin-contacting region and a fluidic layer.

131. The device of claim 130, wherein the hollow structure facilitates sensitive-skin protection, biofluid sampling, targeted fluid routing, or any other functional requirement of the device.

132. The devices of any one of claims 130-131, wherein the at least one skin contacting layer is comprises at least one addilional layer designed to enhance comfort, breathability, mechanical compliance, moisture management, and / or secure attachment to the skin.

133. The devices of any one of claims 130-131, wherein the fluidic layer 710 may collect, wick, or transport biofluid — such as breast milk, interstitial fluid, sweat, or any combination thereof — to at least one sensor 712 for chemical, biochemical, electrochemical, ophcal, or mechanical analysis.654905-3262-5274, v. 1134. The devices of any one of claims 130-134, further comprising a processor that is electrically and / or fluidically coupled to the sensor.

135. The devices of any one of claims 130-135, wherein the processor may perform any of the following functions: signal processing; analog or digital Filtering; amplification; application of current or voltage waveforms; wireless or wired power transfer; wireless or wired data communicarion; on-device computation; local data storage; sensor calibration; temperature compensation; timing control; or activation of valves, pumps, or dissolvable membranes.

136. The devices of any one of claims 130-135, wherein, the device comprises one or more barrier layers 718 configured to enhance mechanical integrity, provide insulation or dielectric barriers, protect internal components, increase robustness against bending or compression, or otherwise support the structural or functional operation of the device.

137. The devices of any one of claims 130-136, wherein the processor is communicatively coupled to coils, antennas, or other electronic structures enabling wireless communication (e.g., RFID, NFC, Bluetooth), inductive power transfer, resonant sensing, or additional electronic functionalities.

138. The devices of any one of claims 130-137, wherein the device may additionally include at least one colorimetric sensing region fluidically connected to the fluidic layer.

139. The device of any one of claims 130-138, wherein, the device may include a color indicator chart positioned on the device surface to enable quantitative or semi-quantitative biomarker analysis by visual comparison or by digital imaging via a smartphone or external reader.

140. The device of any one of claims 130-139, further comprising one or more fluidic processing layers.

141. The device of any one of claims 130-140, wherein the skin-contacting layer 704 or the barrier layer 718 contain openings that allow fluid to exit or enter the device.

142. The device of any one of claims 130-141, wherein the barrier layer includes one or more openings that permit controlled fluid release or transfer, facilitate user comfort, or enable active breastfeeding while the device remains in place.664905-3262-5274, v. 1143. The device of any one of claims 130-142, further comprising a removable strip located at any suitable region of the device.

144. The device of any one of claims 130-143, further comprising one or more regions configured to store or preserve biofluid for later analysis, archival, or shipment to a processing center.

145. The device of any one of claims 130-144, wherein the fluidic layer is introduced through hollow channels or structural conduits within the device.674905-3262-5274, v. 1

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