Devices and methods for processing human milk

Abstract

Methods, devices, and systems for processing breast milk are described. Concentrating nutrients in breast milk may be achieved using an apparatus comprising at least one forward osmotic membrane. In an example, the apparatus can include a forward osmotic membrane enclosing a draw material, and arranged so that water can traverse the forward osmotic membrane. In an example, the apparatus is configured to draw water from un-concentrated, expressed human milk to form concentrated human milk. In some examples, the apparatus can include a sorbent material to remove contaminants. In some examples, the apparatus can include supplements to fortify the milk. The apparatus may include sensors for monitoring, leak detection dyes, tracking indicia, gelling stabilizers, and other features. The apparatus may be provided as a multi-component kit or system.

Description

70569-WO-PCT / MMIB TITLE Devices and Methods for Processing Human Milk CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application 63 / 640,862, filed April 30, 2024, which is incorporated herein in its entirety. TECHNICAL FIELD

[0002] This disclosure relates in general to methods of processing consumable liquids. Embodiments of the invention provide devices, systems, and methods to concentrate, purify, fortify, treat, and process breast milk, such as by concentrating nutrients within breast milk, in particular for premature babies. Additionally other liquids and bodily fluids can be processed for administration to humans or animals. BACKGROUND

[0003] Mother’s own milk (MOM) has unique nutritional and health benefits for preterm infants and reduces neonatal morbidity, mortality and NICU costs in a dose-dependent manner. Feeding preterm infants MOM improves brain, vision, microbiome and immune system development and reduces the incidence of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and neonatal sepsis. MOM is a complex, biologically active form of nutrition; its composition fluctuates due to maternal hormonal and dietary influences. Artificially replicating MOM would be incredibly complicated, predictably expensive, and not foreseeable in the near future. Consequently, increasing MOM intake by preterm infants is a public health priority.

[0004] Premature babies often require supplements to add nutrients to expressed human breast milk. Available supplements frequently contain cow's milk protein and / or soy. One human milk fortifier available is made with pooled human milk that is pasteurized, destroying some of the nutrients found in fresh expressed human milk. These supplements are often the first foreign substances introduced to a baby's gut. The risk of intolerance of traditionally fortified feedings is most notable for the potential development of necrotizing enterocolitis, which can lead to gut damage and even death.70569-WO-PCT / MMIB

[0005] Even when abundantly available, MOM is generally not a sole nutrient source for preterm infants due to their high nutrient needs and lower volume tolerances. Most NICUs in the United States fortify MOM and donor human milk (DHM) with bovine milk-derived fortifiers, which are one of the only readily available, low-cost options to promote adequate extrauterine growth. However, the use of bovine milk-derived fortifiers in preterm infant feeding may impact human milk components and impact the risk of morbidities. Donor human milk (DHM)-derived fortifiers are also available but are more limited in use due to their higher cost, concerns about ethical sourcing, and a lack of proven efficacy. DHM-derived fortifiers have also been linked to an increased incidence of hypoglycemia, compared with feeding with bovine milk-derived fortifiers. Moreover, DHM-derived fortifiers displace as much as 50% of MOM to achieve a caloric density adequate for preterm infant growth. Thus, despite the challenge in providing adequate nutrients, feeding preterm infants fresh MOM should be prioritized for optimal growth.

[0006] Premature infants are often born to mothers who had birth complications that required medical intervention, including administration of systemic medicines, such as pain treatments and antibiotics. Some medicines, such as anti-depressants, hormones, antibiotics, and analgesics, may be advisable for a woman following a birth, but inadvisable if breastfeeding. Additionally, mothers with addiction or drug abuse problems may use drugs. These circumstances can lead to the presence of medicines, drugs, and other unwanted substances in breast milk. It would be desirable to provide methods and systems to process MOM to reduce and remove unwanted substances while retaining the substantial benefits of breastmilk.

[0007] Premature babies often require supplements to add nutrients to expressed human breast milk. Available supplements contain cow's milk protein and / or soy. One human milk fortifier available is made with pooled human milk that is pasteurized, destroying some of the nutrients found in fresh expressed human milk. These supplements are often the first foreign substances introduced to a baby's gut. The risk of intolerance of traditionally fortified feedings is most notable for the potential development of necrotizing enterocolitis, which can lead to gut damage and even death.

[0008] Thus, there is a need for new and improved methods, devices, and systems for concentrating and processing breast milk.70569-WO-PCT / MMIB SUMMARY

[0009] Provided is a device to concentrate fluids including, mother’s own milk (MOM). In some examples, the device can be attached to a cap, integrated into a container, or separately provided for use in a container. The container can hold a fluid - including bodily fluids. The container or device or both can aid in the transfer of additional supplements or the removal of substances from the fluid. The container or device or both can detect concentrations of various elements or characteristics of the fluid. The internal contents of the device can stop the transfer through gel or solidification of internal components. The device can be removed from the cap or container leaving the processed fluid to remain in the container.

[0010] According to the teachings herein, one method described herein includes placing, into contact with a quantity of un-concentrated, expressed human milk, a forward osmotic membrane separating a material exhibiting an osmotic draw property from the quantity of un- concentrated, expressed human milk to draw water from the quantity of un-concentrated, expressed human milk to form concentrated human milk, and withdrawing the forward osmotic membrane from contact with the concentrated human milk when the concentrated human milk reaches a desired nutrient level. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The drawings are provided for selected embodiments and not all possible implementations; the drawings are provided for illustrative purposes only, and are not intended to limit the scope of the present disclosure.

[0012] FIG. 1 depicts an example method and system for processing milk.

[0013] FIG. 2A depicts another example method and system for processing milk.

[0014] FIG. 2B shows an example container according to one or more embodiments described herein.

[0015] FIG. 3 shows an example device according to one or more embodiments described herein.

[0016] FIG. 4 schematically depicts a cross-section of the device of FIG. 3.

[0017] FIGS. 5A 5B 5C depict examples of a sheet cross-section of the device of FIG. 4.

[0018] FIG. 6 shows an example device according to one or more embodiments described herein.70569-WO-PCT / MMIB

[0019] FIG. 7 shows an example container or processing vessel according to one or more embodiments described herein.

[0020] FIG. 8 shows an example device and container according to one or more embodiments described herein.

[0021] FIG. 9 depicts an example processing system according to one or more embodiments described herein. DETAILED DESCRIPTION

[0022] Described are methods, devices, and systems for concentrating nutrients within breast milk. The teachings herein provide methods and devices for the concentration of human milk, including donor milk or a mother's own milk, for a premature or sick baby to the prescribed nutrient density optimal for growth and development. Some example devices are suitable for bedside use, and the addition of foreign nutrients and heat processing may be avoided. The concentration of immunoglobulins, such as IgA, and other unique nutrients that are provided in a mother's milk can be achieved without external pressure and by forward osmosis to protect fragile nutrients in the breast milk that can be damaged even by shaking the liquid too forcefully. The use of a forward osmotic membrane without nitrates provides a system for conservation of the immunoglobulin on the nutrient concentration side of the membrane and only water passes via forward osmosis to the other side of the membrane. The process can be performed efficiently to mitigate or prevent damage to time-sensitive components of breast milk. The process facilitates efficient nutrient concentration.

[0023] According to the teachings herein, a method can include placing, into contact with a quantity of un-concentrated, expressed human milk, a forward osmotic membrane separating a material exhibiting an osmotic draw property from the quantity of un-concentrated, expressed human milk to draw water from the quantity of un-concentrated, expressed human milk, to form concentrated human milk, and withdrawing the forward osmotic membrane from contact with the concentrated human milk when the concentrated human milk reaches a desired nutrient level.

[0024] An example HMC device or apparatus can include a forward osmotic membrane, arranged so that water can traverse the forward osmotic membrane to an interior, and a draw material within the interior exhibiting an osmotic draw property to draw water from un- concentrated, expressed human milk to form concentrated human milk.70569-WO-PCT / MMIB

[0025] Premature babies can benefit from ingesting a more nutrient-rich sustenance than provided by un-concentrated, expressed human breast milk. Mother’s own milk (MOM) has unique nutritional and health benefits for preterm infants and has been shown to reduce neonatal morbidity, mortality, and costs for a neonatal intensive care unit (NICU). Feeding preterm infants MOM improves brain, vision, microbiome and immune system development and reduces the incidence of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and neonatal sepsis. MOM is a complex, biologically active form of nutrition; its composition fluctuates due to maternal hormonal and dietary influences. Consequently, increasing MOM intake by preterm infants is highly desirable.

[0026] Passive osmotic concentration can be used as a point-of-care approach to increasing the nutrient and bioactive content of MOM that avoids heat and pressure damage and displacement of MOM. This process can use osmotic draw across a limited permeable membrane to remove only the smallest molecules (<0.0007 micron), such as water, from HM. One specific embodiment of such an approach is a single-use human milk concentration (HMC) device composed of an osmotic membrane packet that is added to fresh or thawed HM and promotes passive concentration of HM components outside the device by removal of a defined amount of water. For broad accessibility and implementation, some embodiments of the HMC device were developed with attention to standard NICU feeding workflows, cost limitations, and compatibility with 50 mL to 240 mL breast pump milk collection containers, including bags and bottles.

[0027] Turning now to FIG. 1, an example method is shown. A volume of unconcentrated expressed breast milk is provided in a container 200, and a device 100 for human milk concentration (HMC) is prepared and provided in the form of a pouch. The milk is human milk (HM), and may be a mother’s own milk (MOM) or donor human milk (DHM). The expressed breast milk may be fresh, stored, or thawed. The pouch may be single-use, disposable pouch. In some examples, preparing the pouch can include wetting the pouch, for example by placing it in warm sterile water for 5-60 seconds, then removing it form the warm water, and excess water may be shaken off. The device 100, is placed into the container 200 and contacts the expressed breast milk. As depicted in FIG. 1, left side, a container with a volume of unconcentrated fluid is provided, the volume or fill level 210 of the container prior to inserting the device can be at a first measured level. The device is placed into the container in contact with70569-WO-PCT / MMIB the fluid. After a contact time, the device 100 is removed from the container as shown on the left side of FIG. 1. During the contact time, water enters the device, whereby, upon removal the volume or fill level 210 of fluid in the container is decreased, and the remaining fluid in the container is concentrated. The device comprises a osmotic membrane enclosing a draw material, and can be provided as packet or pouch that is added to fresh or thawed HM, in a container, and provides passive concentration of HM components outside the pouch by removal of water. In some examples, the device can remove a defined amount of water.

[0028] The device contacts the expressed breast milk for contact time. The milk may be warmed during the contact time. The milk may be kept at a refrigerated storage temperature during the contact time. The expressed breast milk is liquid, or at least partly liquid, during the contact time.

[0029] In some examples, a contact time, from a time of placing the forward osmotic membrane of the device into contact with the expressed breast milk in the container, to a time of removing the device from contact with the concentrated breast milk, is a predetermined time. The period of time can be a preset period, such as between 10 minutes and 24 hours. The period of time can be a preset period determined by preparation conditions. As an example, a contact time, while warming the milk from a first temperature in a range of 4°C - 25°C to a feeding temperature in a range of 30°C - 38°C, may be about 25 minutes, or in a range between 10 to 120 minutes. As another example, a contact time, while storing the milk in a refrigerator or cooler at a temperature of about 4°C, or in a range of 3°C - 12°C, the preset contact period may be about 3 hours, or in a range of 1 hour to 24 hours.

[0030] In another example, a contact time can be determined by a reduction in volume. For example, an initial volume can be recorded for the expressed breast milk, and the initial volume may be compared with a concentrated volume. For example, the pouch may be lifted out of the milk in the container to view the concentrated volume. In some examples, the contact period is selected to end when the volume in the container, excluding the volume in the pouch, has decreased from the initial volume by about 25%, or by between 5% to 50%, by between 10% to 45%, by between 15% to 40%, by between 15% to 30%, by between 20% to 35%, or by between 20% to 30%.

[0031] The device 100 is removed from the container 200 at the end of the contact time. The container holds a volume of concentrated breast milk which may be used for feeding70569-WO-PCT / MMIB immediately or stored for later feeding. The example device 100 shown in FIG. 1 is a disposable, single use pouch which can be discarded after being removed from the container.

[0032] The device may be used while HM is stored under refrigeration or being warmed for feeding. The device has been shown to increase the concentrations of macronutrients and bioactive molecules in samples of previously frozen, pasteurized and unpasteurized HM. A proof-of-concept study was performed on previously frozen donor HM. The HM samples sets were analyzed after concentration at temperatures equivalent to milk storage or feeding preparation in US NICUs. (4°C / refrigeration, 20°C room temperature or 37°C HM warming temperature) and results compared to baseline HM nutrient analysis. Validation of Water Removal and Concentration of Nutrients and Other Milk Components

[0033] As shown in Table 1, below, nine human milk components were analyzed pre and post concentration. The results validated that removing ~20% of water from Mother’s Milk using the HMC increases nutrients. All but one component, leptin, was concentrated. Given the variation in human milk, the standard variations were high, however 4 components did concentrate significantly.

[0034] Table 1: Human Milk Components Component Method Result (% Statistical Concentration) Significance70569-WO-PCT / MMIB Component Method Result (% Statistical Concentration) Significance

[0035] mno acds were aso concenraed. g -perormance qud c romaograp y was used to measure amino acids. As shown in Table 2, below, all analyzed amino acids were concentrated.

[0036] Table 2: Amino Acid Concentration Amino Acid Concentration70569-WO-PCT / MMIB Histidine 40±17% Serine 39±13% Point-of-care ConcentratioFresh Human Milk Samples

[0037] Fresh HM samples were assessed and measured for bioactives (including: lactoferrin and IgA), select micronutrients, osmolarity, pH, Sodium, macronutrients (including: fat, protein, and carbohydrates), stem cells, active enzymes, oligosaccharides, fatty acids and small molecules; 46 tests in total. Below are the summarized results where HMC verified is defined as the Human Milk Concentration Device removed water from the milk and increased the nutrient (Table 3). Results indicate passive osmotic concentration of fresh HM can concentrate HM components by selective removal of water. HM osmolality and pH remained within standard neonatal feeding range guidance by the American Academy of Pediatrics and human milk parameters at baseline.

[0038] Table 3: Human Milk Components Concentrated Component Method Result (% Paired t test Concentration) [Nutrient ]>[Nutrient l]70569-WO-PCT / MMIB Component Method Result (% Paired t test Concentration) [Nutrientfinal]>[Nutrientinitial]70569-WO-PCT / MMIB Component Method Result (% Paired t test Concentration) [Nutrientfinal]>[Nutrientinitial]

[0039] Turning to FIG. 2A and 2B, another example method is shown. A volume of unconcentrated expressed breast milk is provided in a container 200, and a device 100 is provided in or formed into a receptacle or recess 310 of a cap or lid 300. The recess 310 can contain a draw material enclosed by a forward osmotic membrane. In one example, the device 100 can be provided as pouch seated into a recess 310 of the lid 300. In another example, the recess 310 can have a set volume, defined by the lid recess dimensions and by the forward osmotic membrane, and that volume is partly filled with the draw material. The forward osmotic70569-WO-PCT / MMIB membrane can be fitted across and secured to a circumferential portion of an inside of the cap, thereby enclosing the draw material and defining the enclosed volume of the recess.

[0040] FIG. 2A shows, on the left, a container 200 to which the liquid has been added. The middle portion of FIG. 2A shows the step of attaching the lid 300 containing the device 100 to the container 200. And the right side of FIG. 2A depicts inverting the container 200 to bring the membrane of the device 100 into contact with the liquid.

[0041] Once the human milk has been disposed within the container 200 and the lid 300 is attached to the container 200, the bottle can be inverted to bring the liquid into contact with the device 100 and begin the process of concentrating the human milk. Water passes through the forward osmotic membrane, toward the draw material, to fill the recess 310. The volume of the recess can be sized to accommodate the draw material and a selected volume of water. By configuring the amount of draw material and the enclosed volume in a non-expandible recess 310, an upper limit of the amount of water removed can be set. Once an amount of water is drawn through the membrane that is sufficient to fill the receptacle 310, the remaining breast milk can have the desired concentration level of nutrients. This method and system can be used to prevent over concentration and can be time-insensitive, providing schedule flexibility. For example, a container of liquid could be left in a refrigerator on one work shift and used to feed an infant on a subsequent work shift with little regard for tracking time of preparation.

[0042] Turning to FIGS. 3-4, an example device is shown. The device 100 has an effective width, x, height, y, and thickness, z. The effective dimensions relate to the size of the functional portions of a pouch or packet, excluding an edge seal 190, if present. In some embodiments, one of the dimensions is altered during use. In one example, the surface area of the device remains unchanged while the thickness increases as water enters the device and fills an interior or inner chamber 450 of the device. Additional examples can be provided with pleats or folds to increase the available interior volume to accommodate additional expansion.

[0043] FIG. 4 shows a cross section of the device of FIG. 3 along line 4-4. In the example shown, a pocket or pouch is formed from two sheets, joined by a peripheral edge seal 190, and enclosing an interior chamber 450. The interior chamber 450 can contain a draw material. The two sheets can include a forward osmotic membrane. The device can have an interior surface 410 and an exterior surface 490. In the example shown, a pouch can be formed with two forward osmotic membrane sheets including a first sheet 111a and a second sheet 111b.70569-WO-PCT / MMIB A first sheet is joined to a second sheet such that the first sheet 111a, and the second sheet 111b are arranged back-to-back such that the osmotic draw is to the interior 450. The first sheet 111a and the second sheet 111b can be sealed about most of the edge surface using a press or other techniques, including, for example by the application of heat. One example of sealing about most of the edge surface when membrane sheets 111 are rectangular involves sealing about three of the four edges. Optionally, membrane sheets may be sealed with similarly-sized sheets of a laminate film to form the seal 190 about a portion of the outer perimeter.

[0044] FIG. 5A, FIG. 5B, and FIG. 5C depict a cross-sectional view of the sheet 111 of the device 100. The sheet layer, sheet layer stack, or sheet 111 encloses and defines the inner volume or inner chamber 450 of the device. A device can be formed with one or more sheets 111, 111a, 111b. The sheet is water permeable. The sheet 111 can comprise a plurality of layers. FIG. 5A, FIG. 5B, and FIG. 5C show some examples of a sheet layer stack 111 for a cross- section segment 5 of FIG. 4. FIG. 5A shows a sheet comprising core layer 510, which can be an osmotic membrane. FIG. 5B illustrates a core or inner layer 510 at the interior surface 410, and an outer layer 590 at the exterior surface 490. FIG. 5C illustrates a core, first layer, or inner layer 510 at the interior surface 410, a third layer or an outer layer 590 at the exterior surface 490, and an interior, second or intermediate layer 550 between the inner layer 510 and the outer layer 590. In one example, the device comprises an outer layer and an inner layer and a pore size of an outer layer is more than 1000 times greater than a pore size of the inner layer; in one example, a pore size of an outer layer is between 1,000 to 100,000 times greater than a pore size of an inner layer.

[0045] In some embodiments, the inner layer encloses an inner chamber 450 of the device. In some embodiments, the inner layer encloses and is directly adjacent to the inner chamber 450. In some embodiments, the outer layer is configured to contact milk. In some embodiments, the outer layer may have a soluble coating. In some embodiments, an additional layer or partial layer may be disposed over a portion of the outer layer, thereby the outer layer is between the additional layer and the inner layer.

[0046] The sheets 111 of the device may be formed of a plurality of materials such as a polyethylene or polyester substrate with cellulose and a drying agent, such as glycerin. Preferably, at least the outside-facing surfaces of the layer stack 111 are approved for contact with food. The glycerine can serve to seal micropores in the substrate to protect the micropores70569-WO-PCT / MMIB from being sealed by the draw material. Other materials that can help maintain pore structure include polymeric additives, sugars, polyols, proteins, amino acids, and salts.

[0047] FIG. 6 shows some features of a device 100. The device may have packaging 650. The packaging may include removable packaging, for example: a backing, a housing, a wrapping, a packet, a sachet, a bag, a box, a sleeve, a tray, or a film. The device may have an internal compartment or partition 670. The internal partition can separate functional areas of the device. For example, the device can be configured to remove water to concentrate a fluid external to the device, the device can be configured to administer supplements, and / or to remove substances from the liquid; internal partitions can separate portions with differing porosity and compositional features to simultaneously effectuate these goals.

[0048] The device 100 may have an access port 615. The access port may be configured for extraction or insertion. The access port can include a valve, such as a sampling valve, cap, straw, seal, tube, or spout. The device may have a removal aid 620 to facilitate removing the device 100 from a container 200. The removal aid 620 may include a string, loop, hook, adhesive, or handle.

[0049] The device 100 or its packaging 650 may have one or more indicators 630. For example, a device may include indicators for conditions that change or are detected, such as: temperature, pH, swelling, time exposed to liquid, or presence of a detected chemical. An indicator on packaging may further include, for example, tamper indicators and autoclave exposure.

[0050] The device 100 or its packaging 650 may have one or more tracking identifiers or indicia markers 640. For example, a device or packaging may include a patient identifier, a barcode, a patient classification, a device characteristics label, a medical indication, a supplement type, and / or a RFID tag.

[0051] In some embodiments, the device may have a transparent or translucent portion or view window 660. In some examples the interior of a device includes a color-changing feature viewable through the window 660. In some examples a color-changing feature is embedded into a sheet 111, or provided on an interior surface 410 or exterior surface 490 of the device.

[0052] In some embodiments, the device or its packaging includes an alert 690 to indicate one or more parameters outside of a desired range.70569-WO-PCT / MMIB

[0053] Turning now to FIG. 7, FIG. 8, and FIG 9, examples of containers and systems with containers are shown.

[0054] In some embodiments, the device 100 is provided for use in a system with a vessel or container 200. A container 200 can have measurement indicia 246. The container 200 can have a primary opening 215 and one or more secondary container ports 225. A lid can have a secondary lid port 325. A lid can be provided with a feeding accessory 335, such as a nipple, tube, or straw. The container 200 and / or lid can be provided in packaging 750. The container 200, or lid 300, or packaging can have real-time gauges, sensors, or indicators 730, an alert display 790, and tracking, identification, or indicia markers 740.

[0055] FIG. 8 shows an example system with a container 200, a lid 300, and a device 100 attached or incorporated into the container 200.

[0056] FIG. 9 shows an example system with a container 200, a lid 300, and a device 100 attached or incorporated into an extension from the lid 300. FIG. 9 also shows a monitoring system 900 with a communication path 950 from a device sensor or indicator 630, and from a container sensor 730, to a monitoring station 960. In the example depicted, the monitoring station includes memory 910, a processor 920, a look-up table or sensor monitoring 930, and a display or other interface 940. The monitoring station can be communicatively coupled through the communication channel 950 to the

[0057] In some examples, the device 100 comprises at least one forward osmotic membrane, at least one laminate film, and a draw material. In some examples, the osmotic membrane forms a pouch around an interior volume or interior chamber 450. In some examples, the pouch comprises at least one of: a drying agent- organic, inorganic or polymer additives, or cellulose, glycerine, polyethylene glycol, calcium chloride, silica gel, magnesium sulfate, polyvinylpyrrolidone, cellulous derivative, activated alumina, phosphorus pentoxide, a polyester substrate, polyethylene substrate, high-density polyethylene (HDPE), low-density polyethylene (LDPE), medium-density polyethylene (MDPE), resin, polylactic acid (PLA), ethylene polymer, or a thermoplastic resin. Draw solutions could include dextrose, glucose, magnesium chloride, calcium chloride, potassium chloride, sucrose, hydrogel, poly(N-isopropylacrylamide), magnetic nanoparticles, sodium polyacrylate, polystyrene sulfonate, functionalized silica nanoparticles, three dimensional hydrophilic polymers, alginate, chitosan, hyaluronic acid, polyacrylamide (PAM), polyvinyl alcohol (PVA), polyethylene glycol, poly(N-isopropylacrylamide) (PNIPAM).70569-WO-PCT / MMIB

[0058] A draw material can be contained within an interior 450 of the device 100. In one example, a pouch encloses, contains, or comprises: approximately 2g of draw material by dry weight. In some examples, the pouch contains between 1g to 250g draw material, 5g to 100g draw material, 15g to 100g draw material, 15g to 80g draw material, 10g to 60g draw material, 15g to 50g draw material, 10g to 30g draw material, or 1g to 20g draw material or lower. For larger packet sizes for use in milk banks or pooled milk for home use, the pouch contains between 10g to 1500g draw material, 100g to 1500g draw material, 150g to 1000g draw material, 150g to 800g draw material, 100g to 600g draw material, 150g to 500g draw material, 100g to 300g draw material, or 200g to 400g draw material.

[0059] The amount of draw material is selected based on the amount of water to be drawn from the expressed milk. The amount may be selected based in part on the size of the forward osmotic membrane. For example, the same amount of draw material would draw water faster when used with a forward osmotic membrane having a larger surface area than one having a smaller surface area. The draw material used for drawing the water across the forward osmotic membrane may be a carbohydrate. In an example, the draw material can include one or more of: sucrose, dextrose, or lactose. Mixtures of various dry carbohydrates can also be used. The form of the dry carbohydrate can include, but is not limited to, a fine powder or pellets.

[0060] In an example, an interior of the device can further include a gelling agent, and water drawn into the pouch may be bound by the gelling agent. In some examples, the device encloses, contains, or comprises: between 1.0g to 25g of the gelling agent by dry weight. In some examples, the device encloses, contains, or comprises a gelling material and a draw material, wherein a ratio of the gelling agent to the draw material by dry weight is equal to or greater than 1:10. In some examples, the ratio between the gelling material to the draw material by dry weight is less than or equal to 10:1. In some examples, the device comprises a gelling agent and a draw material at a ratio in a range from 1:5 to 5:1; or in a range from 1:3 to 3:1.

[0061] The method can include selecting a device size. The size can be selected in conjunction with the selection of the amount of draw material, and may be dictated by the application, such as the size of the container 200 in which the liquid will be processed.

[0062] In some examples, a device 100 can have a surface area greater than 20 cm2, 30 cm2, 40 cm2, 50 cm260 cm2, 70 cm2, 80 cm2, 90 cm2, 100 cm2, 150 cm2, or 200 cm2. In some examples, a pouch 106, 300 can have a surface area less than 1000 cm2, 800 cm2, 600 cm2, 50070569-WO-PCT / MMIB cm2450 cm2, 400 cm2, 300 cm2, 250 cm2, 200 cm2, 180 cm2, 150 cm2, or 100 cm2. In some examples, a device 100 can have a surface area in a range of: 20 cm2to 400 cm2, or can have a surface area of about 35 cm2to 175 cm2. The device 100 can also be sized for pooled breast milk contained in 1-15L batches in human milk banks. In some examples, a device 100 can have a surface area greater than 200 cm2, 300 cm2, 400 cm2, 500 cm2600 cm2, 700 cm2, 800 cm2, 900 cm2, 1000 cm2, 1500 cm2, or 2000 cm2. In some examples, a device 100 can have a surface area less than 10000 cm2, 8000 cm2, 6000 cm2, 5000 cm24500 cm2, 4000 cm2, 3000 cm2, 2500 cm2, 2000 cm2, 1800 cm2, 1500 cm2, or 1000 cm2. The device would fit in a 15L container including a cylindrical container of diameter 25cm by 31 cm, rectangular container of 25cm x 20 cm x 30cm or square based container 20cm x 20cm x 37.5 or smaller container. The device would fit in a 1L container including a cylindrical container of diameter 10cm by 13 cm, rectangular container of 10cm x 5 cm x 50cm or square based container 10cm x 10cm x 10 cm. Storage techniques

[0063] In various embodiments, the human milk concentration device may be stored using one or more preservation techniques tailored to the nature of its internal components, functional requirements, and intended use environment. These storage configurations are designed to maintain device efficacy, sterility, and ease of activation while also supporting extended shelf life and compliance with clinical workflows.

[0064] In a wet storage configuration, the membrane or other important components of the device are maintained in a hydrated state, often submerged in a sterile aqueous solution within a sealed compartment. This approach ensures that the membrane remains pre-wetted and ready for immediate use without requiring a separate activation step. Wet storage is particularly advantageous in clinical settings where rapid deployment is essential, and user handling should be minimized.

[0065] In a dry storage configuration, the device, including the membrane, is stored in a fully dehydrated state within the packaging. This method supports long-term shelf stability under ambient conditions, reduces product weight, and facilitates compact storage and distribution. Dry storage is also compatible with cleanroom-based dry-fill packaging processes, making it well- suited for high-volume or sterile manufacturing environments.

[0066] A third configuration involves vacuum-sealed storage, in which the device— whether wet, moist, or dry—is enclosed within a vacuum-sealed package. By removing air, this70569-WO-PCT / MMIB method significantly reduces the risk of oxidation, microbial growth, or other degradation pathways. Vacuum sealing enhances both sterility and biological stability, making it ideal for devices incorporating sensitive nutritional, enzymatic, or supplement components.

[0067] In some embodiments, combination storage techniques are employed. These configurations feature multiple compartments or sub-chambers within the packaging, each optimized for the specific needs of its contents. For instance, the membrane may be stored in a wet or semi-hydrated state in one compartment, while a separate supplement chamber is kept dry and vacuum-sealed. This hybrid approach facilitates selective activation of different functional zones within the device while preserving sensitive additives in their most stable form. It further supports staged workflows, aiding caregivers to activate, mix, or dose components at time of use.

[0068] The packaging may also include additional features to support usability, integrity, and regulatory compliance, such as tamper-evident seals, high-barrier films that resist moisture and oxygen ingress, single-use peel-open designs for rapid access, and internal compartments designated for supplements, indicators, or sensor modules. These features may be combined in various configurations to ensure the device remains safe, effective, and easy to deploy across clinical, home, or field settings. Activation

[0069] In certain embodiments, the human milk concentration device includes a membrane or pouch that preferably uses activation prior to, or during use, in order to initiate optimal performance. The activation process is aids in initiating the membrane’s selective permeability, assisting it in the process to remove water or other small molecules while preserving essential nutrients such as proteins, lipids, and bioactive compounds. Activation can be achieved through passive or user-initiated mechanisms, depending on the specific storage configuration, end-user setting, or clinical workflow.

[0070] In one embodiment, activation is achieved via an internal packaging component. In this design, a sterile activation agent—typically a buffered aqueous solution—is sealed within the same compartment or adjacent chamber as the device or pouch. Upon opening the packaging or removing the pouch from its sterile enclosure, the liquid automatically contacts the membrane, triggering immediate activation. This pre-activation-on-removal technique simplifies use by removing the need for separate user action, and is particularly advantageous in fast-paced clinical settings where ease of use, consistency, and time efficiency are essential.70569-WO-PCT / MMIB

[0071] In another embodiment, the membrane is stored in a dry or semi-dry state and use methods include rinsing with sterile water or a prepared solution immediately prior to use. The rinsing step serves to hydrate the membrane and restore its permeability characteristics. This method is especially valuable for dry-stored devices, as it facilitates extended shelf life during storage, while still supporting a controlled and simple activation protocol. Caregivers or users may rinse the device externally or activate it using a built-in rinse compartment, depending on the system design. Rinsing instructions may be included in the package insert to aid proper execution.

[0072] In yet another embodiment, the device is designed for passive activation upon contact with human milk. In this approach, the membrane self-activates when immersed in milk, eliminating the need for any prior preparation. This embodiment is particularly well-suited for home use or disposable systems, where simplicity and intuitive use are paramount. The surface chemistry of the membrane is engineered to support rapid hydration, with consideration for typical milk viscosity and temperature, ensuring that activation occurs in a predictable and efficient timeframe.

[0073] These activation strategies may be customized or combined within a single device design. For instance, a vacuum-sealed device may incorporate a rupturable internal sachet containing an activation fluid that is released upon pressure or peeling. This hybrid approach provides both storage protection and automatic activation upon use. Additionally, visual indicators, such as color-changing strips or swelling markers, may be incorporated into the membrane or housing to signal successful activation to the user.

[0074] The flexibility in activation mechanisms provides significant advantages. It supports both clinical-grade reliability and consumer-facing simplicity, reduces the risk of user error, enhances shelf readiness, and facilitates high reproducibility in the concentration process. The ability to choose or combine activation methods is compatible for the system to adapt to a wide range of user preferences, workflow settings, and regulatory requirements. Supplements

[0075] In various embodiments, the human milk concentration device may be designed to deliver nutritional, therapeutic, or functional supplements in conjunction with the milk concentration process. These supplements may be included directly within the device, embedded on structural components, or supplied as part of the device packaging. The inclusion of70569-WO-PCT / MMIB supplements is intended to streamline feeding workflows, enhance nutritional delivery, and reduce the complexity and potential for error during preparation. Supplement integration may be configured as either passive—where supplements are gradually released into the milk—or active, where release is triggered by user action, temperature, flow, or physical mixing.

[0076] Several delivery mechanisms are envisioned for integrating supplements into the system. In one embodiment, supplements are pre-loaded inside the device, stored within an internal compartment or chamber that mixes with the milk during or after concentration. In another configuration, supplements may be embedded adjacent to or within the membrane itself. These formulations may be micro-encapsulated or layered as coatings, which dissolve or release their contents upon membrane hydration or activation. In some cases, supplements are sealed within the packaging, supplied as a separate blister, sachet, or capsule. These are opened by the user and mixed with the milk at the time of use.

[0077] Additional delivery mechanisms include modular or snap-on supplement cartridges, which can be magnetically or mechanically affixed to the device prior to or during use. Dissolvable films or disks may also be adhered to the inner surfaces of the device; these release their contents passively as milk flows over or into contact with them. Another variant includes supplement-coated or impregnated interior surfaces, where nutrients or functional agents are embedded in the device lining and dissolve upon exposure to fluid.

[0078] Supplements may be delivered in various form factors, including freeze-dried powders, micronized formulations, liquid concentrates, emulsions, pre-measured tablets or gelcaps, microcapsules or beads, dissolvable films or wafers, or as aerosols or sprays in sealed internal compartments. In an example, a supplement is provided in a water-soluble, film- forming polymer adhered to a portion of the sheet layer stack. In some examples, the film- forming polymer comprises one or more of: pullulan, gelatin, sodium alginate, starch, or carrageenan.

[0079] The types of supplements that may be used with human milk span a broad range of nutritional, developmental, and therapeutic categories. These include: 1. Vitamins, such as vitamin D and polyvitamin blends (A, D, E, K, and B-complex), as well as vitamin C. 2. Minerals, including calcium, phosphorus, iron, zinc, and magnesium. 3. Macronutrient fortifiers, such as protein concentrates (e.g., whey protein or hydrolyzed peptides), lipid supplements (e.g., MCT oil, omega-3 fatty acids), and carbohydrate enhancers (e.g., maltodextrin, glucose70569-WO-PCT / MMIB polymers). 4. Human Milk Oligosaccharides (HMOs), including 2’-fucosyllactose (2’-FL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 3’-sialyllactose (3’-SL), and 6’- sialyllactose (6’-SL). 5. Functional bioactives, such as choline, phosphocholine, betaine, phosphatidylcholine, sphingomyelin, nucleotides, and taurine. 6. Enzymes and immunological factors, including lactoferrin, secretory IgA (sIgA), bile salt-stimulated lipase (BSSL), lysozyme, glutathione peroxidase, and catalase. 7. Electrolytes and micronutrients, such as sodium, potassium, chloride, selenium, and copper. 8. Energy boosters, including concentrated fat derivatives, glucose polymers, and total solids fortifiers. 9. Therapeutic additives, such as probiotics (e.g., Bifidobacterium, Lactobacillus), prebiotics (e.g., inulin), or specialized medications (e.g., amino acid blends for metabolic disorders), administered in accordance with clinical oversight.

[0080] The integration of supplements into the device provides numerous advantages. It eliminates the need for multi-step manual mixing by caregivers, reduces the potential for dosing errors, and improves compatibility with standardized NICU workflows. Furthermore, supplement release can be precisely timed to occur only after milk has been concentrated, ensuring that the final feed volume reflects both the intended nutrient density and the correct supplement dose. This system supports personalization of nutrition based on infant-specific needs, including those related to prematurity, gastrointestinal tolerance, immune function, or metabolic disorders. Selective Pore Size

[0081] Variable pore sizes of layers in the layer stack can be chosen for selective filtering and nutrient retention. The selective pore size of the membrane or filtration surface within the human milk concentration device is central to its multifunctional capabilities. The design and modulation of pore size can be selected for the device to remove unwanted components, retain and concentrate beneficial nutrients, and selectively deliver or exclude supplements. These features can be tailored to meet the nutritional and therapeutic needs of individual infants, particularly those in clinical or neonatal care settings.

[0082] In various embodiments, the membrane may be fabricated with a pore size ranging from as small as 0.0001 angstroms to as large as 10,000 nanometers, with more ideal ranges falling between 0.1 angstroms and 100 nanometers, depending on the intended function. The membrane material may be polymeric, ceramic, nanocomposite, or biologically derived,70569-WO-PCT / MMIB with precision-engineered structures that provide tightly controlled filtration and permeability properties.

[0083] A primary function of pore size control is water removal, for the concentration of human milk. In this application, pores are designed to allow the passage of water and small solutes while retaining larger, essential molecules such as proteins (e.g., lactoferrin and immunoglobulins), human milk oligosaccharides (HMOs), and lipids. The result is a nutrient- dense milk concentrate that maintains or enhances caloric and immunological value.

[0084] In some embodiments, the membrane also facilitates the retention and controlled release of supplements. When supplements are preloaded within the device or embedded on the membrane, the pore size can be optimized to retain important macromolecules such as enzymes and proteins within the milk, or to moderate the release rate of encapsulated supplement ingredients. This ensures that nutrients are delivered at the appropriate time and dose, while preventing premature leaching during storage or early stages of use.

[0085] Pore design also plays an important role in the removal of harmful substances, such as ethanol, cannabinoids and other cannabis-derived compounds such as THC, and pharmaceutical residues. By targeting the molecular weight, polarity, genetic fingerprint, and hydrophilicity of these substances or biologic substances, the membrane can selectively exclude them from the concentrated milk, providing a safer nutritional product for sensitive populations, including premature or medically compromised infants.

[0086] Additionally, the membrane may be configured to provide filtration of viruses and microbial contaminants. Pore sizes in the range of 20 to 200 nanometers can be used to exclude common enveloped viruses such as cytomegalovirus (CMV), as well as bacterial pathogens and microbial spores. This function is especially relevant for processing donor milk, which may carry a higher risk of exposure to environmental contaminants.

[0087] In more advanced embodiments, the membrane may feature multiple filtration layers, or spatially zoned pore regions, for the selective passage or retention of compounds by size. For example, an inner membrane or core layer may filter water and small solutes, an intermediate layer may handle mid-sized additives or biomolecules, and a outer layer may preserve large immune factors or growth-related peptides. Such designs provide custom filtration profiles, and the same device can be adapted across a range of therapeutic or nutritional scenarios.70569-WO-PCT / MMIB

[0088] Furthermore, the membrane may support dynamic or responsive pore modulation. In certain configurations, the pore size may change in response to chemical, mechanical, or thermal triggers. For instance, the membrane may be fabricated with materials that swell or contract based on pH, ionic concentration, fluid pressure, or temperature, such that the user or clinical setting can control its filtration characteristics in real time.

[0089] The ability to modulate and customize pore size confers several benefits. It maximizes nutrient retention while eliminating undesired compounds, supports personalized feeding protocols, facilitates compatibility with both clinical and home use, and reduces the likelihood of user error related to supplement dosing or exposure to harmful agents. The system’s flexibility in pore design and behavior ultimately enhances its value as a safe, adaptive, and effective solution for infant nutrition management.

[0090] A corresponding table may further define common human milk components, contaminants, and supplement ingredients, their approximate molecular size, whether they should pass through or be retained by the membrane, and the rationale for their filtration behavior. This supports the optimization of membrane design and performance for specific clinical or nutritional applications.

[0091] Table 4: Substances that pass in and out of milk Substance / Desired Direction Approximate Size Purpose / Com onent Rationale e70569-WO-PCT / MMIB Lactoferrin, IgA, Retain in milk 4–15 nm Important immune Enzymes and digestiveConcentrated substances or constituents

[0092] Some substances that can be concentrated include: 2’-fucosyllactose (2'-FL), lacto-N-difucohexaose I (DFLNT), lacto-N-hexaose (LNH), disialyllacto-N-tetraose (DSLNT), 3-fucosyllactose (3FL), lacto-N-neotetraose (LNnT), sialyl-lacto-N-tetraose c (LSTc), disialyllacto-N-hexaose (DSLNH), 3’-sialyllactose (3'-SL), fucosyllacto-N-hexaose (FLNH), difucosyllacto-N-hexaose (DFLNH), difucosyllactose (DFLAC), lacto-N-tetraose (LNT), sialyl- lacto-N-tetraose b (LSTb), fucosyl-disialyllacto-N-hexose ( FDSLNH), 6’-sialyllactose (6'SL), lacto-N-fucopentaose I (LNFP I), lacto-N-fucopentaose II (LNFP II), lacto-N-fucopentaose III ( LNFP III) free choline, phosphocholine, betaine, phosphatidylcholine (PC) and sphingomyelin, SPH), Free choline, phosphocholine and betaine, Fatty acid content, sodium, protein, lactose,70569-WO-PCT / MMIB lactoferrin, and active IgA, betaine and free choline, energy, total solids, lactose, crude protein, true protein, BSSL, Catalse, Glutathione Peroxidase, Lysozyme, PAF-Acetylhydrolase. Monitoring Milk Characteristics: In-device or external monitoring

[0093] In certain embodiments, the human milk concentration device may include features specifically designed to monitor and maintain key physicochemical parameters of the milk—namely pH, osmolality, osmolarity, and viscosity. Monitoring these parameters ensures the safety, stability, and physiological compatibility of the concentrated milk, especially for neonates and preterm infants, who are particularly vulnerable to deviations from nutritional and chemical norms.

[0094] The device may be configured with integrated or attachable sensors capable of continuously or intermittently detecting these important parameters. For example, pH is typically maintained within a safe physiological range of approximately 6.5 to 7.5. Deviations may indicate milk spoilage, contamination, or chemical degradation during handling or storage. Osmolality, ideally kept below 400 mOsm / kg H₂O, is a key indicator of the concentration of solutes and is monitored to avoid feeding intolerance, particularly necrotizing enterocolitis (NEC) in neonates. Osmolarity, typically targeted below 450 mOsm / L, helps prevent excessive renal solute load and supports healthy fluid balance. Finally, viscosity of the milk, which can have a desired consistency within the range of 1 to 3 centipoise (cP),is monitored to ensure safe administration through feeding tubes or bottles, especially when milk is highly concentrated. In some examples, an alert may be triggered if a viscosity exceeds 20 cP, 15 cP, 10 cP, or 5 cP.

[0095] The device may incorporate real-time monitoring systems using either embedded sensors within the milk flow path or external sensing modules that connect to single-use pouches or bottles. Sensor types may include ISFET microelectrodes or colorimetric strips for pH, vapor pressure or freezing-point depression sensors for osmolality, conductivity-based systems for osmolarity estimation, and microcapillary or MEMS-based shear sensors to assess viscosity. Sensors may be permanently integrated into reusable housings or included as modular, disposable strips or probes for contact-based measurement.

[0096] When sensors are present, the system may also feature fail-safe and alert mechanisms. These may include color-coded indicators (e.g., green indicating “safe,” red indicating “warning”), LED displays, or Bluetooth-enabled mobile app interfaces. In more advanced embodiments, the system may include an automatic lock-out mechanism, preventing70569-WO-PCT / MMIB milk administration if any parameter exceeds the preprogrammed safe range. For example, an alert such as “High Osmolality: Discard or Dilute Before Feeding” may be generated for caregiver attention.

[0097] The workflow may involve a multistep monitoring process. A baseline measurement may be taken prior to use, establishing a reference profile for the expressed milk. Real-time monitoring may then be conducted during or after the concentration process, as solute content increases and supplements are optionally introduced. Sensor data is then compared to safe thresholds, either programmed into the device’s logic system or displayed via a connected interface. Finally, user feedback is provided through visual, audible, or app-based alerts to inform feeding decisions.

[0098] These safety systems provide numerous advantages. They help prevent accidental feeding of improperly concentrated or chemically altered milk, ensuring consistency and safety for infants. They support NICU clinical protocols, contribute to digital feeding logs, and offer caregiver reassurance in both hospital and home environments. Furthermore, they support regulatory compliance by providing traceable, real-time monitoring of important safety parameters during the use of the device. Removal of Substances

[0099] In certain embodiments, the human milk concentration device is configured not only to remove water for nutritional concentration, but also to selectively eliminate or reduce harmful substances that may be present in expressed human milk. These substances may include alcohol, cannabis derivatives (e.g., tetrahydrocannabinol, THC), caffeine, nicotine, over-the- counter (OTC) or prescription drugs, and other environmental toxins. This functionality enhances the safety of the milk for infant feeding, especially in neonatal intensive care units (NICUs), donor milk banks, or situations where maternal medication or environmental exposure is unavoidable.

[0100] In certain embodiments, the human milk concentration (HMC) system is designed not only to concentrate beneficial nutritional components but also to selectively reduce or remove exogenous substances that may be present in human milk due to maternal topical exposure. These may include residual chemicals from topical medications, skin treatments, personal care products, or environmental contaminants that are transferred from the skin to the breast during nursing or pumping. The device, through selective membrane filtration, adsorption,70569-WO-PCT / MMIB or chemical sequestration techniques, may be configured to reduce or eliminate substances such as Lanolin and derivatives, commonly found in nipple balms (e.g., Lansinoh®), Moisturizers and emollients including mineral oil, petrolatum, propylene glycol, dimethicone, shea butter, coconut oil, olive oil, and glycerin, as found in commercial eczema creams and lotions (e.g., Eucerin®, Aveeno®, Lubriderm®, Aquaphor®, Cetaphil®, Hempz®), Topical corticosteroids and their carriers, including triamcinolone, emulsifying wax, cetyl palmitate, sorbic acid, and potassium sorbate, Natural oils and essential oils (e.g., lavender, peppermint, tea tree, eucalyptus, lemon, orange, rosemary, frankincense), often used in homemade or organic skincare products and nipple creams; Topical antifungal agents, including nystatin, fluconazole, ketoconazole, clotrimazole, miconazole, and terbinafine; Topical antibiotics such as bacitracin zinc, neomycin sulfate, and polymyxin B sulfate; Sunscreen agents, including zinc oxide, titanium dioxide, avobenzone, oxybenzone, octinoxate, octocrylene, and octisalate; Laundry residues, such as those from detergents like All®, Tide®, and Gain®, which may include ethoxylated alcohols, sulfates, carbonates, and propylene glycol; Soaps and cleansers, including common ingredients like sodium lauroyl isethionate, stearic acid, sodium oleate, and sodium cocoyl isethionate found in Dove®, CeraVe®, and Cetaphil® bars; Powder additives, such as cornstarch, talc, fragrance, and aloe, used in baby or body powders; Fragrance compounds and perfumes, often transferred via body products or air exposure; Environmental toxins, such as microplastics, cigarette smoke, marijuana smoke, and aerosolized vape residues including nicotine, diacetyl, acrolein, diethylene glycol, heavy metals (nickel, tin, lead), and benzene; Insect repellents, including DEET, IR3535, p-Menthane-3,8-diol, 2-undecanone, citronella oil, catnip oil, and oil of eucalyptus; Over-the- counter anti-itch and allergy treatments, including hydrocortisone and diphenhydramine (Benadryl®).

[0101] The device can include one or more sorbent materials to remove, bind, or separate drug contaminants and other undesired substances from the milk. Embodiments may include membrane designs with size-selective pores, affinity layers, or surface chemistries that facilitate the rejection or binding of lipid-soluble, hydrophobic, or molecularly large contaminants while preserving the integrity and concentration of core beneficial milk components such as immunoglobulins, lactoferrin, oligosaccharides, and cellular content. This enhances the safety and clinical applicability of concentrated milk for neonatal consumption, especially for preterm or immunocompromised infants.70569-WO-PCT / MMIB

[0102] One mechanism of removal uses a selective filtration interface. The membrane within the device may be designed with specific pore sizes, surface chemistry, and polarity to allow the passage of low-molecular-weight compounds, while retaining essential macronutrients and immunological components. Removal mechanisms include size exclusion, charge-based separation, affinity filtration, and adsorptive binding. These methods are tailored to retain beneficial compounds such as immunoglobulins (IgA), lactoferrin, human milk oligosaccharides (HMOs), lipids, and bioactive enzymes, while facilitating the passage or entrapment of undesirable substances.

[0103] Compounds targeted for removal may include but are not limited to: ethanol, THC, nicotine, caffeine, and common drugs such as acetaminophen, ibuprofen, antidepressants, amphetamines, and opioids. These substances may be removed through integrated filter layers that incorporate adsorptive or chemically selective materials. The importance of removing such compounds is underscored by clinical evidence: even trace exposure to alcohol or psychoactive substances through breast milk may impair neurodevelopment, lead to hypotonia, feeding difficulties, or sedation, and can complicate care in medically fragile or preterm infants.

[0104] To support this function, certain embodiments of the device incorporate a dedicated adsorptive filtration system, including one or more sorbent materials. This system may include one or more internal layers or chambers containing activated carbon (charcoal) or functionalized carbon-based adsorbents. These materials are selected for their high surface area and ability to bind small molecules through van der Waals forces, π–π stacking, hydrophobic interactions, and electrostatic attraction. Activated charcoal may be presented in various forms, including coated membranes, granular beds, embedded discs, or polymer-carbon composites, ensuring efficient contact with milk while preventing particle shedding.

[0105] Multiple types of activated carbon may be used depending on the application. Activated charcoal offers a broad spectrum of adsorption through micro-, meso-, and macropores. Functionalized activated carbon may include tailored surface chemistries (e.g., hydrophilic, hydrophobic, anionic, or cationic groups) to enhance the capture of specific drug classes. Magnetic activated carbon (MAC) may be used for integration with smart or removable filtration modules. Charcoal-polymer composites provide enhanced biocompatibility and containment, and may be embedded into the inner lining of the device. These charcoal layers70569-WO-PCT / MMIB may be heat-sealed, ultrasonically bonded, or immobilized using polymeric matrices to avoid contamination of the milk.

[0106] Beyond charcoal, a range of alternative or complementary filtration materials may be employed to expand the spectrum of contaminant removal. These sorptive or filtration materials include the materials listed in Table 5. In some embodiments, a sorptive or filtration material can be provided in or on an exterior portion of the device. In some embodiments, the sorptive or filtration material can be provided at an exterior surface of the device. In some embodiments, the sorptive or filtration material can be provided in or on a membrane of the device. In some embodiments, a sorptive or filtration material can be provided with the draw material inside the device.

[0107] Table 5: Types of sorbent material components provided with sheet or draw for substance deactivation or removal Material / Technology Mechanism Target Substances Notes Zeolites Size-exclusion and cation Small drugs ions Natural or le – s nt ; al w70569-WO-PCT / MMIB Activated Alumina Polar surface adsorption Alcohol, fluoride, Stable and ionic drugs widely used in

[0108] Additionally, the device may be configured to remove environmental toxins and biological contaminants. These include heavy metals (e.g., lead, mercury, arsenic, cadmium), persistent organic pollutants (e.g., PCBs, dioxins, PBDEs), pesticide residues, and plasticizers such as bisphenol A (BPA) and phthalates. Other targets may include metabolic waste products, such as excess sodium, chloride, urea, or creatinine, and biological hazards such as viruses (CMV, HIV, HTLV) or bacterial endotoxins. In certain scenarios, the device may also target spoiled milk byproducts, including organic acids and aldehydes that indicate degradation.

[0109] To ensure safety and regulatory compliance, adsorbent materials can be selected to meet biocompatibility and material safety standards. For example, charcoal and additives used for internal milk contact should be USP-grade or certified food-contact safe under FDA CFR Title 21. The efficacy of filtration may be validated using analytical techniques such as high- performance liquid chromatography (HPLC) or liquid chromatography–mass spectrometry (LC- MS / MS), ensuring >90% reduction of target drugs while confirming that health-promoting nutrients remain substantially undiminished.

[0110] This dual-function system—capable of both concentrating nutrients and detoxifying milk—adds significant clinical value. It may provide a process for using milk that would otherwise be discarded, expand eligibility for milk donation, and enhance safety for high- risk infants. It also reduces the burden on caregivers and healthcare staff by providing real-time assurance of milk quality. Integration with optional safety indicators, confirmation strips, or app- connected sensors further reinforces the device’s utility in hospital and home environments. Calculation of Volume Reduction

[0111] The average percentage reduction in fresh HM volume (^^^^^) after passive osmotic concentration using the HMC device was 16.3%±3.8%. Assuming no nutrient loss during passive osmotic concentration, the percentage increase in the content of an HM component (^^^^) is expected to be greater than ^^^^^scaled by the ratio of ^^^^^^^^^^ ^^^^^^,70569-WO-PCT / MMIB as illustrated by the following comparison (where Nabsis the mass of the nutrient and ^^^^^^^^is 75 mL): ^^^^^^^!^^^^^^^ ^^^^"^^^ ^^^^#100=^^^^Therefore,^^^^ > ^^^^^

[0112] The present disclosure relates to a system and method for calculating the volume of human milk before and after a concentration process, thereby facilitating caretakers to determine the specific concentration of nutrients delivered to an infant. Accurate knowledge of milk concentration is fundamental for tailoring nutrition, particularly in neonatal, preterm, or medically complex populations.

[0113] The system can comprise one or more volume measurement components designed to be integrated in various configurations, including: internally within a milk concentration device; externally attached to the device; affixed to a separate milk collection or feeding container; or built directly into the walls or base of the container.

[0114] Volume can be calculated before and after processing by mechanical, electronic, or sensor-based means (e.g., ultrasonic sensors, load cells, or visual indicators), facilitating real- time or near-real-time readouts. The difference in pre- and post-processing volumes is on method used to estimate the concentration ratio of retained nutrients to removed fluid.70569-WO-PCT / MMIB

[0115] The volume measurement module may be passive or active, analog or digital, and optionally linked to a companion mobile or desktop application for logging, tracking, or alerting purposes. The system may include visual indicators or electronic interfaces that display the calculated concentration ratio or provide alerts if the concentration falls outside of a predefined optimal range.

[0116] This process and system helps provide precision in infant nutrition, improves caregiver confidence, and supports clinical accuracy in feeding plans, particularly in neonatal intensive care units (NICUs) and home care settings. Integrated Analytical and Diagnostic Capabilities

[0117] In certain embodiments, the human milk concentration (HMC) device may include or interface with analytical and diagnostic tools that assess the chemical and physical properties of milk before, during, or after concentration. These analytical features provide real- time feedback to the user or clinician, enhancing milk safety, nutritional consistency, and the overall suitability of the milk for infant consumption. Such tools are particularly relevant in NICU settings or at-home use cases where feeding safety and composition verification are of utmost importance.

[0118] These analytical components may be integrated directly into the body of the device, embedded within the membrane chamber, or attached to the container’s interior or exterior. In some versions, they may be supplied in the sterile packaging as standalone disposable sensors, or incorporated into caps, spouts, bottle lids, or other container-access elements. Additionally, users may activate or insert diagnostic tools at the point of use, such as via dipsticks or test strips.

[0119] A variety of analytical mechanisms may be employed. One such tool is the dip strip or test strip, typically composed of a disposable paper or polymer substrate treated with chemical reagents that change color upon contact with milk. These strips may assess pH, glucose, protein levels, bacterial contamination, or drug and alcohol residues through immunoassay or enzymatic indicators. They may be affixed inside the container or supplied externally for single-use analysis.

[0120] Another method uses capillary-based detection, similar to lateral flow immunoassays found in pregnancy tests. A small milk sample migrates across a reactive strip via capillary action, interacting with molecular sensors or labeled antibodies to produce a visible line70569-WO-PCT / MMIB or digital signal. These systems can detect the presence of THC, opioids, lactose, or micronutrients such as vitamin D or choline, making them particularly useful for caregivers monitoring specific dietary or exposure risks.

[0121] In certain embodiments, the device may incorporate or connect to an osmometer, which measures osmolality or osmolarity, prime indicators of milk concentration and solute content. These measurements may be obtained through freezing point depression sensors, electrical conductivity sensors, or vapor pressure devices, with feedback delivered to the user if thresholds such as 400 mOsm / kg H₂O are exceeded—an important safety limit for neonatal feeding.

[0122] To monitor milk acidity, the device may include a pH sensor or indicator, which may take the form of a colorimetric strip, ISFET microelectrode, or pH-sensitive dye window integrated into the housing. Ensuring the pH remains within the physiological range (~6.5–7.5) helps detect spoilage or chemical degradation.

[0123] For more advanced diagnostic needs, such as in research or hospital-grade implementations, the device may utilize Dynamic Light Scattering (DLS) or nanoparticle tracking analysis to determine the size distribution of liposomes, fat globules, or micellar structures. This analysis may also help validate the presence and behavior of added supplements, such as human milk oligosaccharides (HMOs) or emulsions.

[0124] The output of sensor readings may be communicated to the user via visual color change, on-device displays, or digital transmission through Bluetooth, NFC, or QR code scanning linked to a mobile application. This facilitates both caregivers and clinicians to log, interpret, and act on diagnostic information in real-time.

[0125] Practical applications of this integrated diagnostic capability include alerting users if milk pH falls outside a safe range, confirming the success of water removal during concentration, detecting residual drug or alcohol contamination, verifying the presence or dosage of reconstituted supplements, or indirectly monitoring viscosity changes due to protein aggregation or supplement addition.

[0126] These analytical tools significantly enhance the utility of the HMC device by providing an added layer of quality assurance, improving clinical decision-making, and facilitating precision feeding for medically complex or premature infants. Additionally, their70569-WO-PCT / MMIB inclusion strengthens the device’s regulatory profile and offers a compelling advantage in hospital procurement, milk banking, and consumer trust. Safety / Ease of Use: User Safety, Visual Indicators, and Water Immobilization Systems

[0127] The human milk concentration and processing device can include multiple features designed to enhance user confidence, safe handling, and error prevention, particularly for caregivers, clinicians, and parents operating in home or NICU settings. These features provide intuitive feedback mechanisms, minimize the risk of contamination, and ensure that the device is functioning as intended throughout its use cycle.

[0128] One important feature is the immobilization of water extracted from the milk during the concentration process. In certain embodiments, this is achieved through the use of gelling agents, such as superabsorbent polymers (SAPs) or hydrogels, which are capable of transforming liquid water into a stable, semi-solid gel. These materials may be preloaded into the lower section of the pouch, embedded directly within the membrane, or layered into a separate gel-containment chamber. This design helps prevent fluid sloshing, backflow, and leakage— issues that could otherwise compromise sterility, usability, or ease of disposal.

[0129] In some versions, the device may include phase-change materials or thermal elements that solidify water using passive or triggered thermal processes. These mechanisms further reduce contamination risks and ensure the device can be safely discarded in a dry, tamper-resistant state. Whether through physical entrapment or thermal capture, these approaches help caregivers to handle and dispose of the used device without concern for leakage or spillage.

[0130] To reinforce proper usage and boost caregiver confidence, the device may incorporate visual dye indicators that signal successful activation or the completion of water removal. These indicators may involve pH-sensitive dyes that shift color upon hydration, food- safe leaching dyes released into a viewing window upon contact with milk, or colored gel beads that become visible once fluid is absorbed. Trigger mechanisms for these indicators may include direct contact with milk, rupture of a micro-reservoir, or full hydration of the gel zone. Such features can visually confirm that the device has been activated, that water removal has occurred, or that the pouch is ready for disposal—providing important cues for untrained or distracted users.70569-WO-PCT / MMIB

[0131] In some embodiments, the device can include pH-sensitive dyes, oxidation- reduction (redox) indicators, chemical leach indicators, or protein-reactive colorants. These indicators may be incorporated into or adjacent to the membrane, container wall, or sample port to provide a visible cue regarding contamination, material degradation, or unwanted leaching of substances into the milk or processing fluid. Suitable dyes may include, but are not limited to Bromothymol blue, phenol red, or methyl red for pH indication, useful in detecting shifts associated with bacterial contamination or membrane breakdown; Resazurin or methylene blue as redox indicators, which may signal oxidative degradation or the presence of microbial metabolism; Toluidine blue, ninhydrin, or Coomassie brilliant blue, which can interact with proteins or amines, signaling unexpected bioactive residue; UV-activated fluorescent dyes (e.g., rhodamine B, fluorescein) that bind or are released upon contact with leached plasticizers, solvents, or other low molecular weight compounds; Colorimetric indicators sensitive to aldehydes, alcohols, or peroxides, which may be released from plastics, adhesives, or sterilization byproducts (e.g., ethylene oxide residue); Indicator-impregnated strips or films embedded within or affixed to the fluid path to provide continuous, real-time feedback during storage, processing, or transport.

[0132] In certain embodiments, a color change may be irreversible to provide tamper- evidence or a permanent record of exposure, or reversible to enable repeated monitoring under various conditions. The dye may be encapsulated within a permeable matrix, microcapsule, or immobilized on a substrate to prevent direct contact with the milk while still allowing interaction with leachates or chemical indicators of degradation. These systems may enhance the clinical safety of the device by providing immediate visual feedback to the end user regarding possible contamination or chemical instability of the device or its contents.

[0133] In some examples a dye or color indicator can include a food-safe colorant that has a molecular size thar would be contained within an inner portion of the device based on its molecular size being larger than a pore size of a membrane forming the sheet of the device. In one example, a dye has a molecular size in a range of 8-20 angstroms. In an example system, a dye is contained in an inner chamber unless the integrity of the sheet or seal is compromised, which would then be visually apparent by the dye coloring the milk. Similar systems can be used to detect other characteristics of interest, such as by using micro-encapsulated dyes in an encapsulant configured to rupture in the presence of a high osmotic pressure.70569-WO-PCT / MMIB

[0134] Additional safety-focused design features may include self-sealing outlets, lockable closure tabs, or snap-fit seals that close the device once use is complete. The pouch may be constructed with rounded corners, soft edges, and non-reusable materials to prevent misuse or physical discomfort during handling. Devices may also include tamper-evident components that clearly indicate whether the system has been opened or used previously.

[0135] These user-facing features offer numerous advantages. They provide low-tech visual and tactile feedback, improve caregiver trust in the device’s function, and reduce the chance of error without requiring training or digital interfaces. They are particularly valuable in NICU settings, where safety protocols are rigorous. Additionally, these systems support regulatory goals, helping to classify the HMC as a user-friendly, safe, and disposable medical device suitable for broad clinical or home-based deployment.

[0136] The hydrogel and gelling systems themselves play a vital role in water containment. In one embodiment, dry hydrogel powders or beads may be layered at the base of the pouch. As filtered water is drawn through the membrane, the gel swells and locks the water in place. In another configuration, hydrogels may be coated on the membrane, either directly on its surface or sandwiched within a mesh layer, promoting rapid gelation as fluid exits the membrane. Alternatively, a dedicated gel reservoir may be positioned downstream of the concentration chamber, with filtered water directed into the zone for containment.

[0137] Various gelling agents and hydrogel-forming materials may be used to support these applications. These include: • Superabsorbent polymers (SAPs) based on crosslinked polyacrylate chains, which offer extremely high water retention and are used in hygiene products; • Polyacrylamide (PAM) gels, which are transparent and tunable in stiffness; • Sodium polyacrylate, known for absorbing up to 1000 times its weight in water; • Carboxymethylcellulose (CMC), a cellulose-derived hydrophilic polymer used in pharmaceutical and food products; • Gelatin-based hydrogels, which are biodegradable and responsive to temperature; • Alginate hydrogels, which gel via ionic interaction with calcium and are widely used in drug delivery; • Polyethylene glycol (PEG)-based hydrogels, which are biocompatible and FDA- approved;70569-WO-PCT / MMIB • Chitosan-based gels, offering antimicrobial activity and biodegradability.

[0138] These gels may also be enhanced with functional additives, including pH- sensitive dyes, indicator beads, and crosslinking agents that adjust the gel’s viscosity and mechanical strength. These enhancements can provide a system where the gel serves dual roles: both as a water immobilizer and as a visual status indicator.

[0139] The advantages of these systems are numerous. They prevent fluid leakage post- use, facilitate dry and hygienic disposal, and provide caregivers with visual cues indicating the status of water removal. They reduce the risk of cross-contamination and simplify transport or storage of the used device. From a regulatory perspective, these features also help demonstrate compliance with safety standards for leak resistance and biocompatibility—further reinforcing the HMC device’s utility as a comprehensive, user-centric medical system. Shape and form factors.

[0140] In various embodiments, the Human Milk Concentration (HMC) device may take on a wide range of geometrical forms, depending on its intended use case, manufacturing method, integration with ancillary equipment (such as feeding bottles or breast pumps), and user handling preferences. The shape of the device can influence how milk flows through the membrane, how extracted fluid is collected, and how caregivers interact with the system during expression, concentration, or feeding.

[0141] One form is a pouch or bladder shape, which is flexible and collapsible, resembling an IV bag or a breast milk storage pouch. This form is designed to hold milk during the concentration process and expand as milk is introduced. Pouch configurations support gravity-fed flow with minimal backpressure and may include top or bottom ports for inlet and outlet functionality. Variants of this design include flat sealed-edge pouches (created by heat or ultrasonic sealing), double-layer designs with an internal membrane insert, and compartmentalized pouches where the membrane is embedded between discrete fluid layers.

[0142] Another configuration is the cartridge or capsule shape, typically a rigid or semi- rigid body similar in structure to a water filter or capsule-style insert. This shape is often designed to snap into a reusable holder, such as a bottle cap or pump adapter, and may contain a replaceable membrane or filter module. The cartridge form provides a tamper-resistant, easily handled option that is highly compatible with modular systems and bottle-based feeding.70569-WO-PCT / MMIB

[0143] The Device may also be designed as a bottle-integrated system, where the concentration mechanism is built directly into a bottle, liner, or nipple assembly. In this format, milk can be expressed directly into the bottle and filtered during or after expression, eliminating the need for milk transfer or separate pouch usage. Variants include an in-bottle membrane liner, a snap-in or twist-lock capsule located under the bottle cap, or an internal flexible pouch within a rigid outer shell.

[0144] A more technical format is the flat panel or membrane sheet configuration, in which a thin membrane layer is placed between two chambers or containers. This design is suited for use in a “sandwich” configuration, with milk introduced into the upper chamber and concentrated fluid collected in the lower. Flat panel systems can provide even fluid distribution across the membrane and are particularly useful in automated or high-volume settings, such as donor milk banks or NICU batch processing systems.

[0145] In another embodiment, the device may assume a disc or insert shape, which is typically small and circular, designed to sit at the base of a container or connect to a valve system. As milk flows over or through the disc, filtration occurs during expression or feeding. This form is ideal for compact, disposable units or modular inserts that can be quickly swapped out between feedings.

[0146] A tubular or cylindrical form may also be used. In this configuration, milk enters through one end and flows longitudinally through a membrane-lined cylinder, which may include internal baffles or spiral flow channels to extend membrane contact time. The cylinder can be oriented horizontally or vertically and is compatible with both gravity-fed and pressure- assisted operation.

[0147] The device may also take the shape of a cube or brick, offering a solid, rectangular profile with internal compartments or flow channels. This form is beneficial for flat packing, shelf storage, or transport and may include expandable features such as folding walls or telescoping sections that deploy during use.

[0148] For enhanced ergonomics, the device may be configured as a hand-held unit, shaped for one-handed operation with built-in grip zones, soft-touch features, and tactile feedback mechanisms. These designs may include squeeze zones, snap caps, or push-button valves to facilitate controlled fluid movement and user confidence.70569-WO-PCT / MMIB

[0149] A modular or multi-piece assembly may also be employed, particularly in hospital or high-throughput environments. These systems consist of interlocking components such as a reusable shell, a disposable membrane insert, and a supplement capsule chamber. This approach supports interoperability and for different parts of the device to be sterilized, replaced, or customized independently, increasing both cost-efficiency and clinical flexibility.

[0150] Lastly, the Device may be manufactured in asymmetrical or biodegradable forms, tailored for specific use cases. Asymmetrical designs may support compatibility with breast pump hardware, NICU dosing requirements, or compact transport systems. Biodegradable pod shapes may be designed to collapse, dissolve, or safely decompose after use, supporting sustainability goals and regulatory trends in medical waste management.

[0151] Design considerations across these formats include support for stackable storage, hands-free operation, standardized pump and bottle interfaces, and clear visibility of milk volume or concentration status. The materials used may vary by configuration and application, including flexible films such as polyethylene (PE), polyurethane (PU), polyethylene terephthalate (PET), and medical-grade laminates; rigid plastics such as polypropylene (PP) and high-density polyethylene (HDPE); and biopolymers like polylactic acid (PLA) for compostable or eco-friendly variants.

[0152] Alternatively, the device may be preloaded with prepackaged supplements integrated into the draw chamber in a sealed and sterile form. These additions may include single-use capsules or dissolvable sachets, vitamin-enriched emulsions, probiotic beads, or freeze-dried biologics. Upon exposure to the internal environment or fluid contact, these additives dissolve or reconstitute to create a personalized nutritional solution. This feature simplifies caregiver workflows by eliminating the need for separate dosing or mixing steps.

[0153] In more advanced configurations, the device may include one or more resealable openings, for manual or automated access to internal chambers. These openings may be used for refilling, drainage, or adjusting fluid composition, and may also facilitate clinical interventions, such as therapeutic drug delivery. Resealable closures may use mechanical fasteners (e.g., clamps, zip seals), pressure-sensitive adhesives, tamper-evident tear-away zones, hook-and-loop systems, or magnetic and click-lock features. Each closure method is designed to preserve fluid integrity, provide secure resealing, and maintain sterility or biocontainment, particularly important in NICU or clinical environments.70569-WO-PCT / MMIB

[0154] Importantly, the device is suitable for use across a broad range of patient types and settings. It may be used with neonates, preterm infants, older children, adults, and even veterinary patients, including neonatal animals requiring intensive nutritional support. Use cases may involve either the concentrated milk output or the repurposing of extracted fluid for secondary therapeutic applications.

[0155] These design features collectively offer significant advantages. The features can provide personalized nutritional delivery, flexible supplement dosing, and cross-patient usability. They also support both clinical-grade operation and at-home use, while reducing the risk of user error through built-in safety mechanisms and intuitive interfaces. The flexible architecture of the device advances its usefulness to serve as a multifunctional platform adaptable to a wide variety of infant, pediatric, and specialty feeding scenarios. Sealing

[0156] In some embodiments, the device incorporates a semi-permeable membrane securely and durably sealed into the surrounding housing or pouch structure. The interface between the membrane and the device components is configured to be leak-proof, mechanically robust, and chemically stable, particularly in environments involving fluid exposure, pressure differentials, or thermal variation. Proper sealing ensures that milk and filtrate remain separated, filtration efficiency is maintained, and user safety is not compromised.

[0157] The membrane may be joined to a flexible film, rigid frame, or multilayer pouch using a range of sealing methods, applied to two, three, or all four edges of the membrane. In some designs, internal membranes may be sealed along non-rectilinear paths, including radial, spiral, or segmented zones, particularly in disc- or tubular-style configurations.

[0158] One sealing method is heat sealing or thermal bonding, in which compatible polymer layers are heated and compressed to form a continuous fusion seam. This technique can be used for pouch-style devices composed of polyethylene (PE), polypropylene (PP), polyurethane (PU), or laminated films. Heat sealing may be performed on two, three, or four sides of a membrane sheet using impulse sealers, thermal plates, or ultrasonic heat tools, producing strong, uniform seams that are sterile and particle-free.

[0159] Alternatively, the membrane may be joined using adhesive bonding, employing biocompatible medical-grade glues such as silicone-based, polyurethane, cyanoacrylate, or UV- cured epoxy adhesives. The adhesive may be dispensed as a continuous bead, film layer, or70569-WO-PCT / MMIB spray, depending on the application. This method is especially useful when sealing dissimilar materials, such as silicone housing to a polyester membrane, and is beneficial in low-temperature applications or when accommodating complex geometries.

[0160] Ultrasonic welding is another method used in high-precision medical device fabrication. This approach uses high-frequency mechanical vibrations to generate localized heat at the membrane interface, causing controlled melting and fusion of polymer layers without the use of added adhesives. Ultrasonic welding offers rapid cycle times, clean and reliable seals, and minimal thermal damage to adjacent device components.

[0161] In more specialized configurations, mechanical seaming techniques may be used. These may include stitching, looping, or riveting flexible membranes into a housing or outer fabric. While less common in disposable products, mechanical seaming may be useful in reusable or modular devices, especially when combined with a secondary adhesive or sealant layer to achieve leak-proof performance. Stitching also offers visual confirmation of seam integrity and robustness.

[0162] A further approach includes crimping, snap-locking, or overmolding. In these designs, the membrane is mechanically clamped or compressed between two interfacing parts— such as a snap-fit cartridge, gasketed clamp, or injection-molded overstructure. This method can be combined with a gel or adhesive layer to increase sealing integrity. Crimp-based sealing is ideal for modular, serviceable designs and imposes no thermal stress on the membrane.

[0163] Depending on the device form factor, the membrane may be sealed along two opposing sides (e.g., top and bottom for linear flow), three sides to form a U-shaped channel, or all four sides, creating a fully enclosed membrane pocket. Additional geometries include spiral, radial, or segmented seals, facilitating distributed filtration in disc, tubular, or cylindrical formats.

[0164] To ensure leak prevention and quality assurance, devices may include features such as folded seam edges for double-layer sealing, visual inspection zones, or dye-trace paths to verify seal integrity during manufacturing. Post-sealing validation may involve burst pressure testing or peel strength analysis, according to recognized standards such as ASTM F88 and ISO 11607, which apply to sterile barrier systems and medical device packaging.

[0165] These sealing methods and configurations provide important benefits: they preserve sterility, prevent bypass leakage, ensure functional separation of milk and filtrate, and70569-WO-PCT / MMIB support compliance with regulatory sealing standards. Proper integration of these sealing technologies enhances the overall reliability, safety, and usability of the device across both clinical and consumer settings. Concentration volume and detection.

[0166] In various embodiments, the device may incorporate features designed to detect, measure, and indicate the initial and final volumes of human milk during the concentration process. These volume indicators provide essential information for caregivers and clinicians by giving them information to verify that water has been removed appropriately, calculate the resulting nutrient concentration, and ensure consistent feeding volumes and dosing across multiple uses or users.

[0167] This functionality may be implemented using physical volume markers, preset fill thresholds, dynamic indicators, or sensor-based measurement systems. These mechanisms may be integrated directly into the device, pouch, or container, or may exist as external components.

[0168] In one embodiment, the device or container includes volume markers printed or embossed on the surface. These may appear on the external wall of a flexible pouch, a rigid transparent container, or an internal volume chamber. Markers may denote both the starting volume of expressed milk and the target final volume after water removal. The markings can correspond to useful clinical volumes such as 40 mL, 60 mL, 80 mL, or expected post- concentration volumes such as 20 mL or 30 mL, depending on the target concentration ratio (e.g., 2:1 or 3:1). These markers may be preprinted, user-writable with erasable markers, or color-coded or icon-based for use in low-literacy or multi-language settings.

[0169] In some configurations, the device may include preset volume zones or fill thresholds to guide user interaction. These may take the form of a raised ridge, embossed fill line, or a snap-in indicator band that marks the appropriate input volume. These tactile or visual cues help prevent overfilling or underfilling and are particularly useful in settings requiring standardized concentration procedures.

[0170] As the concentration process proceeds, the remaining milk volume may be tracked using dynamic volume indicators. For example, a collapsing internal liner may visibly shrink as fluid is removed. Alternatively, a floating marker may rise or settle within the container to show the current liquid level. Devices may also include a transparent strip or viewing window, for caregivers to visually monitor the concentration in real-time.70569-WO-PCT / MMIB

[0171] For more advanced monitoring, the device may integrate embedded or external volume sensors. These may include load cells for weight-based volume estimation, capacitive fluid level sensors, ultrasonic or optical depth sensors, or pressure-sensitive flow meters. These sensors can connect to hospital monitoring systems or Bluetooth-enabled devices, can be used for digital logging, real-time alerts, and automated dosage calculations, especially valuable in neonatal intensive care units (NICUs).

[0172] In additional embodiments, the system may use marker system additives, such as food-safe dyes or visual indicators, added to the milk prior to concentration. As water is removed, the concentration of the dye increases, providing a visible cue that the concentration process has occurred. These markers may also be measured quantitatively using sensors such as a colorimeter, providing both visual and electronic validation of the concentration endpoint.

[0173] The incorporation of volume detection and marking systems provides several important advantages. It helps ensure accurate nutrient delivery, supports consistent feeding protocols, and reduces the risk of feeding errors, particularly in environments where milk is handled by multiple caregivers. These systems also facilitate automated or app-based tracking, which can be used to monitor trends in infant nutrition and support precision feeding strategies for preterm or medically complex infants. Overall, these features enhance the reliability, usability, and clinical value of the HMC device. Container Integration, Access, Supplement Delivery, and Attachment Methods

[0174] In certain embodiments, the device is configured to be inserted into and remain within a container used for collecting, storing, concentrating, processing, or delivering human milk. This configuration provides features for the concentration process to occur within the same vessel used for milk expression or feeding, streamlining the workflow for caregivers and reducing contamination risks. The device may also incorporate additional features such as supplement delivery, temperature indication, and feed-ready interfaces, all while maintaining ease of use and safety for both caregivers and neonates.

[0175] The device may be inserted into a slot, compartment, partition, or chamber within the container—whether that be a flexible pouch, syringe barrel, or feeding bottle. Once inserted, the device may be fully or partially immersed in milk, and the membrane can be oriented to optimize passive or active water removal. In some designs, the device remains in place during milk withdrawal, including methods such as gravity feeding, syringe-based extraction, or pump-70569-WO-PCT / MMIB driven delivery. After use, the device may either be disposed of along with the container or manually removed if reuse or separate disposal is desired.

[0176] In additional embodiments, the internal contents of the device—such as removed water, infused liquid, or gel—may be accessed and used. This may be accessed through an unsealed edge, removable cap, cuttable top, tear-away strip, or frangible score line, for the user to open a portion of the device in a controlled manner. Once opened, the internal liquid or gel may be repurposed for therapeutic supplementation, such as delivering analgesics, balancing electrolytes, or providing targeted nutrition. The extracted content may be used for the same patient or administered to others via syringe, dropper, or feeding port, and may also find veterinary or topical applications. The internal contents may include fortified nutrients, calming agents, probiotics, prebiotics, or immunomodulatory supplements tailored for neonates or animals.

[0177] To enhance feed safety and user confidence, the device or container may be equipped with a temperature indicator. This may take the form of a color-changing strip or numerical display, positioned on the outer container wall, device surface, or internal liner visible through a viewing window. The temperature strip may be based on thermochromic films calibrated to detect safe feeding temperatures (e.g., 37°C / 98.6°F) or confirm whether the milk remains within appropriate refrigeration ranges.

[0178] To secure the device within the container, a range of attachment and fastening mechanisms may be used. These include adhesives (pressure-sensitive, thermal, or water- activated), mechanical connectors such as clips, hooks, or tabs, magnetic locks, or snap-fit, slot- in, or twist-lock structures. These features help maintain the device in a fixed position during storage, handling, or feeding, and may facilitate optional detachment for cleaning, replacement, or tamper-evident security. In some configurations, the fastening system may include a safety lock that permits removal only after full concentration has occurred.

[0179] Access to the device may be provided via specialized container designs, such as a top-loading access port or a removable film or seal over the membrane compartment. These access points may be constructed from paper, plastic, foil, thermoplastic, polymer, or ceramic materials and may be peelable, tearable, or heat-sealed to preserve sterility until use. The removable film can serve to separate pre-concentration and post-concentration stages, expose the70569-WO-PCT / MMIB supplement or membrane chamber at the point of use, and act as a tamper-evident safety feature to confirm that the device has not been prematurely accessed.

[0180] The container itself may also be configured as a feed-ready system, for milk to be delivered directly through NICU-compatible syringe ports, gravity-fed tubing, or integrated bottle nipples. This design supports hands-free operation, sterile workflows, and low-residue withdrawal, making it highly suitable for clinical environments and neonatal care.

[0181] Overall, these features provide significant advantages. They support workflow modularity and flexibility across both hospital and home settings, provide controlled access to high-value supplemental components, and can provide real-time user feedback through integrated cues for temperature, volume, and concentration. These design features enhance caregiver confidence, improve patient safety, and position the HMC device as a comprehensive, multifunctional solution for safe and personalized milk feeding. Container Documentation, Volume Calculation, and Container-Port Integration

[0182] In various embodiments, the Human Milk Concentration (HMC) system may include integrated features to facilitate documentation, nutrient concentration calculations, and external access to internal compartments via dedicated ports or interfaces. These features are designed to enhance clinical traceability, support accurate nutritional preparation, and streamline workflows in hospitals, donor milk banks, and home-based care settings. In particular, the integration of access ports for sampling and analysis provides enhanced diagnostic flexibility and real-time feedback during milk concentration or supplementation.

[0183] To support documentation and tracking, the device or its associated container may include writable areas or pre-printed labeling zones where essential information can be recorded directly on the product. These labeling fields may include the date and time of milk expression, concentration, or feeding; the temperature during storage or use; and identifying details such as the mother’s name, infant’s ID, or the caregiver or technician involved in milk handling. Additionally, information on the volume before and after concentration, as well as any supplements or additives used, can be noted. Writable areas may be designed to be compatible with dry-erase or permanent marker pens, or covered with adhesive or peel-off labels. Some systems may feature digitally scannable indicia, such as QR codes or barcodes, linking to hospital inventory systems or mobile applications for digital recordkeeping.70569-WO-PCT / MMIB

[0184] To aid in nutrient management, the system may also include an integrated calculation sheet or tool, either as a printed reference on the packaging or device or as a separate insert. These tools help caregivers to determine the percentage of water removed, the final concentration factor, the initial milk volume required to meet a desired output, or the volume of liquid that to be extracted to achieve a targeted concentration. In some embodiments, calculation aids may be sliding rulers, printed grids, look-up tables, or mobile-compatible tools accessed via QR code or NFC chip. These tools are particularly useful in NICU environments, where precision feeding and nutrition tracking are vital to neonatal outcomes.

[0185] An important feature in many embodiments is the inclusion of access ports integrated into the container, device body, or membrane compartment. Examples of access ports 225, 325, 615 are shown in FIGS. 6, 7, and 9. These sampling and analysis ports facilitate spot checks or continuous monitoring of milk characteristics—such as pH, osmolality, glucose levels, electrolyte balance, fat or protein concentration, and microbial presence—without opening the system or compromising sterility. Access ports may also facilitate the injection of supplements, the withdrawal of milk for laboratory analysis, or the confirmation of undesired substance removal, such as alcohol, THC, or pharmaceutical residues. The ports enhance both clinical safety and diagnostic versatility, supporting a broad range of real-time and post-processing evaluations.

[0186] Ports may be located on various parts of the device or container, including the side or base, top cap or collar, membrane chamber, or within ported lids found in bottle- integrated systems. Port designs may vary and include Luer-lock connectors, self-sealing septum ports, twist-lock valves, and sterile tubing channels. These access points may also be equipped with tamper-evident seals, protective caps, or color-coded closures to maintain sterility and clearly indicate sampling or injection zones. Materials used in these components are selected for chemical resistance, gamma irradiation compatibility, or autoclavability, depending on the intended clinical application.

[0187] Table 6: Port Descriptions for container / device access Type Description le a;70569-WO-PCT / MMIB One-way valve port Allows outflow only, preventing back- contamination. y

[0188] The ports can be configured for dual-functionality, for both sampling and additive delivery, or connected to closed-loop in-line probes for real-time electronic monitoring. Some versions may include automatically filling sample reservoirs for batch release testing in donor milk banks or hospital feeding programs. In advanced systems, access ports, or associated tracking markers, may be scannable with RFID or barcodes, for interfacing with electronic milk tracking and documentation systems.

[0189] Beyond their analytical role, ports and external indicators may also serve as visual cues. For example, color-changing fill zones or transparent observation windows may let caregivers visually monitor fluid level changes or concentration status. Pictorial or multilingual instructions may be printed directly on the container, supporting use in low-literacy or high- stress clinical settings.

[0190] These integrated features collectively offer significant benefits. The features enhance clinical documentation, improve nutritional accuracy, and ensure real-time assessment of milk quality. Sampling ports provide repeatable, sterile access without disturbing the system, supporting both hospital-grade diagnostics and home monitoring for vulnerable populations, including premature or immunocompromised infants. When combined with labeling zones and digital connectivity, these features create a comprehensive quality control and traceability framework for human milk concentration and supplementation.

Claims

70569-WO-PCT / MMIB CLAIMS What is claimed is:

1. A device for processing human breast milk into concentrated breast milk, comprising: a sheet comprising at least one forward osmotic membrane; an interior chamber, wherein the sheet encloses and defines the interior chamber; a draw material enclosed within the interior chamber of the device; a leak detection material contained within the interior chamber; a gelling agent within the interior chamber; and at least one sorbent material, wherein the sorbent material, upon contact in a liquid medium, is configured to absorb or adsorb at least one substance; and wherein: the forward osmotic membrane is configured to contact the human breast milk and draw water into the interior chamber, wherein the device draws water from the human breast milk and into the inner chamber of the device to produce concentrated breast milk, whereby between 10% to 35% of water is removed from the un-concentrated, human breast milk; the gelling agent immobilizes at least a portion of water in the interior chamber; and the sorbent material is configured to absorb or adsorb at least one of: ethanol, nicotine, caffeine, acetaminophen, ibuprofen, a cannabinoid, an amphetamine, or an opioid.

2. The device of claim 1, wherein the sorbent material is contained within the interior chamber or integrated into the sheet.

3. The device of claim 1 or 2, wherein the sorbent material comprises at least one of: activated carbon, activated charcoal, charcoal-polymer composites, zeolite, silica-based adsorbent, cyclodextrin, ion-exchange resin, molecularly imprinted polymers, metal–organic frameworks, chitosan-based filter or matrix, hydrogel-based matrix, graphene oxide, activated alumina, or hydrophobic polymers.

4. The device of claim 1 or 2, wherein the sorbent material comprises activated carbon.70569-WO-PCT / MMIB 5. The device of claim 1 or 2, wherein the sorbent material comprises at least two of: activated carbon, activated charcoal, charcoal-polymer composites, zeolite, silica-based adsorbent, cyclodextrin, ion-exchange resin, molecularly imprinted polymers, metal–organic frameworks, chitosan-based filter or matrix, hydrogel-based matrix, graphene oxide, activated alumina, or hydrophobic polymers.

6. The device of any one of claims 1-5, wherein the device comprises the gelling agent and the draw material at a ratio, by dry weight, in a range from 1:5 to 5:

1.

7. The device of any one of claims 1-6, wherein the gelling agent comprises at least one of: polyacrylate polymer, polyacrylamide gels, sodium polyacrylate, carboxymethylcellulose, gelatin-based hydrogel, alginate hydrogel, polyethylene glycol-based hydrogel, chitosan- based gel.

8. The device of any one of claims 1-6, wherein the gelling agent comprises carboxymethylcellulose.

9. The device of any one of claims 1-8, wherein the leak detection material is a non-toxic dye having a molecular size greater than a pore size of the forward osmotic membrane of the sheet, whereby the dye would be visibly present in the milk only if integrity of the sheet was compromised, thereby providing a visual indication.

10. The device of any one of claims 1-9, wherein a pore size of the forward osmotic membrane is in a range of 0.5 nanometers to 20.0 nanometers; or optionally, in a range of 1.0 nm to 10.0 nm, or less than or equal to 0.8 nm.

11. The device of any one of claims 1-10, further comprising a supplement, wherein: the supplement comprises at least one of: a vitamin, a mineral, an electrolyte, a lipid, a carbohydrate, an enzyme, an amino acid, inulin, choline, inositol phosphocholine, betaine, phosphatidylcholine, sphingomyelin, or taurine.70569-WO-PCT / MMIB 12. The device of any one of claims 1-10, further comprising a supplement, wherein: the supplement comprises at least one vitamin; and the supplement is provided in a water-soluble, film-forming polymer adhered to a portion of the sheet, and the film-forming polymer comprises one or more of: pullulan, gelatin, sodium alginate, starch, or carrageenan.

13. The device of any one of claims 1-12, wherein the device comprises two sheets sealed at a peripheral edge, wherein the interior chamber is between the two sheets.

14. A device for processing human breast milk into concentrated breast milk, comprising: a sheet comprising at least one forward osmotic membrane; an interior chamber, wherein the sheet encloses and defines the interior chamber; a draw material enclosed within the interior chamber of the device; and at least one sorbent material, wherein the sorbent material, upon contact in a liquid medium, is configured to absorb or adsorb at least one substance; and wherein: the forward osmotic membrane is configured to contact the human breast milk and draw water into the interior chamber, wherein the device draws water from the human breast milk and into the inner chamber of the device to produce concentrated breast milk, whereby between 10% to 35% of water is removed from the un-concentrated, human breast milk; and the sorbent material is configured to absorb or adsorb at least one of: ethanol, nicotine, caffeine, acetaminophen, ibuprofen, a cannabinoid, an amphetamine, or an opioid.

15. The device of claim 14, wherein the sorbent material is contained within the interior chamber. or integrated into the sheet.

16. The device of claim 14, wherein the sorbent material is integrated into the sheet.70569-WO-PCT / MMIB 17. The device of any one of claims 14-16, wherein the sorbent material comprises at least one of: activated carbon, activated charcoal, charcoal-polymer composites, zeolite, silica-based adsorbent, cyclodextrin, ion-exchange resin, molecularly imprinted polymers, metal–organic frameworks, chitosan-based filter or matrix, hydrogel-based matrix, graphene oxide, activated alumina, or hydrophobic polymers.

18. The device of any one of claims 14-16, , wherein the sorbent material comprises activated carbon.

19. The device of any one of claims 14-16, wherein the sorbent material comprises at least two of: activated carbon, activated charcoal, charcoal-polymer composites, zeolite, silica-based adsorbent, cyclodextrin, ion-exchange resin, molecularly imprinted polymers, metal–organic frameworks, chitosan-based filter or matrix, hydrogel-based matrix, graphene oxide, activated alumina, or hydrophobic polymers.

20. The device of any one of claims 14-19, wherein the device further comprises a gelling agent within the interior chamber.

21. The device of claim 20, wherein the gelling agent is in the interior chamber and the gelling agent is configured to immobilizes at least a portion of water that enters the interior chamber.

22. The device of claim 21, wherein the device comprises the gelling agent and the draw material at a ratio, by dry weight, in a range from 1:5 to 5:

1.

23. The device of claim 20, wherein the gelling agent comprises at least one of: polyacrylate polymer, polyacrylamide gels, sodium polyacrylate, carboxymethylcellulose, gelatin-based hydrogel, alginate hydrogel, polyethylene glycol-based hydrogel, chitosan-based gel.

24. The device of claim 21, wherein the gelling agent comprises a hydrogel material.70569-WO-PCT / MMIB 25. The device of any one of any one of claims 14-24, further comprising a leak detection material.

26. The device of claim 25, wherein the leak detection material is in the interior chamber.

27. The device of claim 26, wherein the leak detection material is a non-toxic dye having a molecular size greater than a pore size of the forward osmotic membrane of the sheet, whereby the dye would be visibly present in the milk if integrity of the sheet is compromised during use.

28. The device of claims 27, wherein the pore size of the forward osmotic membrane is in a range of 0.5 nanometers to 20.0 nanometers.

29. The device of any one of claims 14-28, further comprising a supplement, wherein: the supplement comprises at least one of: a vitamin, a mineral, an electrolyte, a lipid, a carbohydrate, an enzyme, an amino acid, inulin, choline, inositol phosphocholine, betaine, phosphatidylcholine, sphingomyelin, or taurine.

30. A system for processing human breast milk into concentrated breast milk, comprising: a device, the device comprising: a sheet comprising at least one forward osmotic membrane; an interior chamber, wherein the sheet encloses and defines the interior chamber; a draw material enclosed within the interior chamber of the device; and at least one of: a leak detection material contained within the interior chamber; a gelling agent within the interior chamber; or at least one sorbent material, wherein the sorbent material, upon contact in a liquid medium, is configured to absorb or adsorb at least one substance, wherein the substance comprises at least one of: ethanol, nicotine, caffeine, acetaminophen, ibuprofen, a cannabinoid, an amphetamine, or an opioid.; and wherein:70569-WO-PCT / MMIB the forward osmotic membrane is configured to contact the human breast milk and draw water into the interior chamber, wherein the device draws water from the human breast milk and into the inner chamber of the device to produce concentrated breast milk, whereby between 10% to 35% of water is removed from the un-concentrated, human breast milk.

31. A method comprising: placing, into contact with a quantity of un-concentrated human milk, a device, wherein the device comprises: a sheet comprising at least one forward osmotic membrane; an interior chamber, wherein the sheet encloses and defines the interior chamber; a draw material enclosed within the interior chamber of the device; and at least one sorbent material, wherein the sorbent material, upon contact in a liquid medium, is configured to absorb or adsorb at least one substance; and wherein: the forward osmotic membrane is configured to contact the human breast milk and draw water into the interior chamber, wherein the device draws water from the human breast milk and into the inner chamber of the device to produce concentrated breast milk, whereby between 10% to 35% of water is removed from the un-concentrated, human breast milk; and the sorbent material is configured to absorb or adsorb at least one of: ethanol, nicotine, caffeine, acetaminophen, ibuprofen, a cannabinoid, an amphetamine, or an opioid.

32. The method of claim 31, comprising removing the device from contact with the human milk after a contact time in a range of 30 minutes to 24 hours.

33. The method of claim 31 or 32, comprising monitoring at least one of the milk, a container for the milk, or the device.

34. The method of any one of claims 31-33, wherein the concentrated breast milk has between70569-WO-PCT / MMIB 1.1 to 2.0 times the Kcal per ounce, as compared with the expressed breast milk.

35. A kit for performing the method of claim 31, comprising the device and a container.

36. A device for concentrating human milk comprising a pouch or housing with a semi- permeable membrane configured to remove water while retaining nutritional components.

37. The device or method of any claim herein, wherein the device includes a gelling material to immobilize extracted water within the pouch.

38. The device or method of any claim herein, wherein the membrane is sealed on two or more sides using heat, adhesive, ultrasonic welding, or mechanical attachment.

39. The device or method of any claim herein, wherein the device includes a supplement chamber that promotes delivery of nutrients into the milk.

40. The device or method of any claim herein, wherein the supplement chamber is accessible through a resealable cap or port.

41. The device or method of any claim herein, wherein the membrane has a pore size tunable to selectively remove water, alcohol, drugs, or toxins while retaining larger molecules.

42. The device or method of any claim herein, wherein a colorimetric indicator or dye signals activation or successful concentration.

43. The device or method of any claim herein, wherein one or more sensors are included to monitor pH, osmolality, osmolarity, or viscosity.

44. The device or method of any claim herein, wherein the device or container includes volume markers for pre- and post-concentration tracking.

45. The device or method of any claim herein, wherein a temperature strip is affixed to the container or device to indicate milk temperature.

46. The device or method of any claim herein, wherein the device is integrated into or attachable to a feeding container, bottle, or syringe-based system.

47. The device or method of any claim herein, wherein the container includes writable areas for time, date, temperature, and user ID.70569-WO-PCT / MMIB 48. The device or method of any claim herein, wherein the container or device includes one or more sampling ports for milk withdrawal or sensor insertion.

49. The device or method of any claim herein, wherein the sampling port is a luer-lock, self- sealing septum, one-way valve, or screw-cap port.

50. The device or method of any claim herein, wherein a film or peel strip is used to expose or activate the membrane within the container.

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