Systems and methods for applying skin probiotics

Abstract

A system comprising a handle assembly with a plunger movable in response to user actuation of an actuator, and a pod assembly coupled to the handle assembly. The pod assembly includes an outlet, a skin probiotic, and a fluid. The skin probiotic and the fluid are dispensed from the outlet in response to user actuation of the actuator.

Description

TAXA-44420601SYSTEMS AND METHODS FOR APPLYING SKIN PROBIOTICSRELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 753,499 filed February 4, 2025, which is incorporated herein by reference in its entirety for all purposes.FIELD

[0002] The present invention relates to devices, systems, and methods for dispensing and applying at least one probiotic or probiotic composition to a subject, for example, human skin.BACKGROUND

[0003] Body odors, particularly those originating from sweat, represent a significant irritant for many humans. Sweat released from glands through the body is a complex solution of salts, minerals, metabolites, and other components. Once secreted, sweat provides a nutrient filled solution for skin microbiota to use for replication. Unfortunately, this replication, and the incumbent high levels of metabolic activity, results in the production of a number of undesirable byproducts, including volatile thioalcohols, which give off a distinct and unpleasant smell commonly referred to as body odor.

[0004] Conventional antiperspirants prevent the body from engaging in natural cooling mechanisms. Conventional deodorants, meanwhile, do not prevent the generation of body odor, but merely conceal it with a more potent odor and, in some cases, provide antimicrobial ingredients to reduce bacterial activity and abundance. Both antiperspirants and deodorants are environmentally costly to manufacture, produce significant amounts of plastic waste, and ty pically require multiple applications over a penod of days to retain efficacy.SUMMARY

[0005] One aspect of the present disclosure provides an assembly comprising a housing with an outlet, a composition, and a fluid. The assembly is movable between a first configuration and a second configuration. The composition and the fluid are separated in the first configuration. The composition and the fluid are at least partially combined and dispensed through the outlet in the second configuration.

[0006] In some embodiments, the composition is at least one skin probiotic.TAXA-44420601[0007J In some embodiments, the at least one skin probiotic is genetically engineered.[0008J In some embodiments, the at least one skin probiotic comprises a Staphylococcus strain, a Cutibacterlum strain, a Corynebaclerium strain, a Bacillus strain, a Micrococcus strain and / or a Lactobacillus strain.

[0009] In some embodiments, the at least one skin probiotic comprises a Coagulasenegative Staphylococci (CoNS).

[0010] In some embodiments, the at least one skin probiotic comprises one or more of S'. hominis, S. lugdunensis, S. haemolyticus, S. epidermidis. and / or S’, cohnii.

[0011] In some embodiments, the at least one skin probiotic is genetically engineered to comprise a disruption in at least one endogenous gene.

[0012] In some embodiments, the at least one skin probiotic comprises a Staphylococcus hominis strain having a disrupted patB gene.

[0013] In some embodiments, the at least one skin probiotic comprises a Staphylococcus hominis strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof.

[0014] In some embodiments, the at least one skin probiotic comprises a Staphylococcus lugdunensis strain having a disrupted patB gene.10015] In some embodiments, the at least one skin probiotic comprises a Staphylococcus lugdunensis strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof.[0016| In some embodiments, the at least one skin probiotic comprises a Staphylococcus haemolyticus strain having a disrupted patB gene.

[0017] In some embodiments, the at least one skin probiotic comprises a Staphylococcus haemolyticus strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof.10018] In some embodiments, the at least one skin probiotic is formulated as a desiccated skin probiotic powder.

[0019] In some embodiments, the at least one skin probiotic is formed as a tablet.TAXA-44420601[0020J In some embodiments, in the second configuration, the fluid pushes at least a portion of the at least one skin probiotic through the outlet and re-hydrates the at least one skin probiotic.

[0021] In some embodiments, viable colony-forming units (CFUs) are delivered by dispensing the fluid through the outlet.

[0022] In some embodiments, the tablet comprises about 0.1% to about 90% (w / w) lyophilized skin probiotic powder.

[0023] In some embodiments, the desiccated skin probiotic powder or tablet retains at least 10% of an initial viable CFU count after storage for at least 1 day.

[0024] In some embodiments, the storage is for at least 7 days.

[0025] In some embodiments, the storage is for at least 1 month.

[0026] In some embodiments, the storage is for at least 6 months.

[0027] In some embodiments, the fluid is a water-based fluid.

[0028] In some embodiments, the water-based fluid is an aqueous solution, an aqueous gel, an aqueous cream, or a combination thereof.

[0029] In some embodiments, the water-based fluid includes silk peptides, xanthan gum, diutan gum, hyaluronic acid, or any combination thereof.10030] In some embodiments, the fluid is preservative free.

[0031] In some embodiments, the fluid is gamma or electron beam irradiated.

[0032] In some embodiments, the moving from the first configuration to the second configuration requires an external force acting upon the assembly.

[0033] In some embodiments, moving from the first configuration to the second configuration causes the fluid to move toward the composition to at least partially combine with the composition.

[0034] In some embodiments, moving from the first configuration to the second configuration causes the composition to move toward the fluid to at least partially combine with the fluid.TAXA-44420601

[0035] In some embodiments, moving from the first configuration to the second configuration causes the composition and the fluid to move toward a mixing zone where the composition and the fluid are at least partially combined.

[0036] In some embodiments, the composition is positioned between the fluid and the outlet in the first configuration.

[0037] In some embodiments, the fluid is positioned between the composition and the outlet in the first configuration.

[0038] In some embodiments, the composition is positioned a first distance from the outlet in the first configuration, and wherein the fluid is positioned a second distance from the outlet in the first configuration; and wherein the first distance is equal to the second distance.

[0039] In some embodiments, the composition is at least partially surrounded by the fluid in the first configuration.

[0040] In some embodiments, the fluid is at least partially surrounded by the composition in the first configuration.

[0041] In some embodiments, the composition is positioned within the housing in the first configuration, wherein the fluid is positioned within the housing in the first configuration. |0042] In some embodiments, the assembly further comprises a cartridge, and wherein the fluid is positioned within the cartridge.

[0043] In some embodiments, the cartridge includes a cartridge housing and a seal coupled to the cartridge housing.[0044| In some embodiments, the cartridge housing includes an aperture and wherein the seal covers the aperture in the first configuration; and wherein the seal is broken in the second configuration.

[0045] In some embodiments, the assembly further comprises a puncture member positioned within the housing.10046] In some embodiments, the outlet is at a first end of the housing and the housing includes a connector at a second end of the housing opposite the first end.

[0047] In some embodiments, the second end of the housing includes an opening configured to receive a plunger.TAXA-44420601[0048J In some embodiments, the outlet is partially formed by a stem with a plurality of apertures.

[0049] In some embodiments, the housing includes an upper body and a lower body; wherein the outlet is formed in the upper body.

[0050] In some embodiments, the lower body includes a window to receive a pip formed on the upper body.

[0051] In some embodiments, the assembly further comprises a cartridge, wherein the fluid is positioned within the cartridge, and wherein the lower body includes an opening such that the cartridge is mechanically accessible through the opening.

[0052] In some embodiments, the cartridge includes a housing with a recess formed in a bottom surface.

[0053] In some embodiments, the assembly further comprises a puncture member positioned within the housing, and wherein the composition is at least partially positioned within the puncture member in the first configuration.

[0054] In some embodiments, the composition is formed as a tablet, and wherein the puncture member includes a cavity and at least one retaining rib extending into the cavity and configured to secure the tablet within the cavity.

[0055] In some embodiments, the outlet is partially formed by a stem in the housing, and wherein the puncture member is at least partially positioned within the stem.

[0056] In some embodiments, the puncture member includes at least one piercing element formed at an end.

[0057] In some embodiments, the assembly further comprises a first sealing member positioned between a cartridge for the fluid and the housing; and a second sealing member positioned between a puncture member and the housing.|0058] In some embodiments, the composition is positioned within a first cartridge and the fluid is positioned within a second cartridge.

[0059] In some embodiments, the first cartridge includes a first cartridge housing, a first seal coupled to the first cartridge housing, and a second seal coupled to the first cartridge housing.TAXA-44420601[0060J In some embodiments, the first seal and the second seal are broken in the second configuration.

[0061] In some embodiments, the first cartridge housing includes a first aperture at a first end and a second aperture at a second end, opposite the first end; and wherein the first seal covers the first aperture in the first configuration and the second seal covers the second aperture in the first configuration.

[0062] In some embodiments, the first cartridge is positioned between the outlet and the second cartridge.

[0063] In some embodiments, the first cartridge and the second cartridge are positioned within a channel of the housing and are movable with respect to the housing.

[0064] In some embodiments, the first cartridge and the second cartridge abut the channel.

[0065] In some embodiments, the assembly further comprises a puncture member positioned between the first cartridge and the second cartridge.

[0066] In some embodiments, the puncture member includes a first piercing element positioned on a first side configured to open the first cartridge and a second piercing element positioned on a second side, opposite the first side, configured to open the second cartridge.|0067] In some embodiments, the puncture member includes at least one opening configured to receive the fluid in the second configuration.

[0068] In some embodiments, in the second configuration, the second cartridge moves with respect to the housing to cause the puncture member to abut the second cartridge and the first cartridge to thereby open the second cartridge and the first cartridge.

[0069] One aspect of the present disclosure provides a system comprising a handle assembly w ith a plunger movable in response to user actuation of an actuator; and a pod assembly coupled to the handle assembly. The pod assembly includes an outlet, a composition, and a fluid. The composition and the fluid are dispensed from the outlet in response to user actuation of the actuator.

[0070] In some embodiments, the handle assembly defines a center axis; and wherein the plunger translates along the center axis in response to user actuation of the actuator.

[0071] In some embodiments, user actuation of the actuator includes rotation of the actuator about the center axis.TAXA-44420601[0072J In some embodiments, the pod assembly is removably coupled to the handle assembly.

[0073] In some embodiments, the pod assembly and the handle assembly form a bayonet style interface.

[0074] In some embodiments, the composition is at least one skin probiotic and the at least one skin probiotic is genetically engineered and is formulated as a desiccated skin probiotic powder or as a tablet.

[0075] In some embodiments, the fluid is preservative free and is sterilized.

[0076] In some embodiments, the composition is positioned within a cartridge that includes a cartridge housing, a first seal coupled to the cartridge housing, and a second seal coupled to the cartridge housing, and wherein the first seal and the second seal are broken in response to user actuation of the actuator.

[0077] In some embodiments, the fluid is positioned within a cartridge that includes a cartridge housing and a seal coupled to the cartridge housing; and wherein the seal is broken in response to user actuation of the actuator.

[0078] In some embodiments, the composition is at least one skin probiotic and the fluid pushes the at least one skin probiotic through the outlet and re-hydrates the at least one skin probiotic in response to user actuation of the actuator.

[0079] In some embodiments, user actuation dispenses colony -forming units (CFUs) of viable skin probiotics from the outlet.

[0080] In some embodiments, the desiccated skin probiotic powder or tablet retains at least 10% of an initial viable CFU count after storage for at least 1 day.

[0081] In some embodiments, the storage is for at least 7 days.

[0082] In some embodiments, the storage is for at least 1 month.

[0083] In some embodiments, the storage is for at least 6 months.10084] In some embodiments, the plunger extends into the pod assembly in response to user actuation of the actuator.

[0085] In some embodiments, the plunger retracts in response to the pod assembly being removed from the handle assembly.TAXA-44420601

[0086] One aspect of the present disclosure provides a handle assembly comprising a housing defining an axis, a pressure body movable with respect to the housing between a first position and a second position, a sleeve including an aperture, a plunger having an outer surface with a helical groove, at least one spring that biases the pressure body to the first position, an actuator including a stem coupled to the plunger for co-rotation with the plunger about the axis, and a ball positioned in the aperture formed in the sleeve. The ball is positioned outside the helical groove when the pressure body is in the first position; and wherein the pressure body retains the ball within the helical groove when the pressure body is in the second position. The plunger moves with respect to the housing along the axis to an extended position in response rotation of the actuator about the axis when the pressure body is in the second position. The plunger moves with respect to the housing along the axis to a retracted position by the bias of the at least one spring when the plunger is in the extended position and in response to the pressure body moving from the second position to the first position.

[0087] In some embodiments, the at least one spring is a spring positioned between the pressure body and the plunger.

[0088] In some embodiments, the at least one spring includes a first spring positioned between the pressure body and the sleeve, and wherein the at least one spring includes a second spring positioned between the plunger and the sleeve; wherein the first spring biases the pressure body to the first position; and wherein the plunger moves with respect to the housing along the axis to a retracted position by the bias of the second spring.|0089] In some embodiments, the pressure body moves with respect to the housing along the axis between the first position and the second position.

[0090] In some embodiments, the pressure body includes an end wall and a side wall; wherein an opening is formed in the end wall, and wherein a bore is formed by the side w all and the end wall.

[0091] In some embodiments, the side wall includes a contact surface configured to abut the ball.

[0092] In some embodiments, the plunger extends through the opening.

[0093] In some embodiments, the at least one spring is positioned within the bore, and wherein a first end of the at least one spring abuts the end wall of the pressure body and a second end of the at least one spring abuts a flange of the plunger.TAXA-44420601

[0094] In some embodiments, the at least one spring biases the pressure body away from the sleeve.

[0095] In some embodiments, the sleeve is stationary- relative to the housing.

[0096] In some embodiments, the sleeve includes a first cylindrical wall portion, a second cylindrical wall portion, and a ledge extending between the first cylindrical wall portion and the second cylindrical wall portion; wherein the aperture is formed in the first cylindrical wall portion.

[0097] In some embodiments, the handle assembly further comprises a retention ring with a finger extending through a notch formed in the ledge.

[0098] In some embodiments, the actuator includes a snap finger coupled to the ledge of the sleeve.

[0099] In some embodiments, the plunger does not translate along the axis in response to actuation of the actuator when the pressure body is in the first position.

[0100] In some embodiments, when the pressure body is in the second position, the plunger translates along the axis relative to the stem in response to the stem and the plunger co-rotating about the axis.|0101] In some embodiments, the stem is non-circular.10102] In some embodiments, the actuator only rotates about the axis in one direction.

[0103] In some embodiments, the handle assembly further comprises a pawl positioned on the actuator and a plurality of teeth formed on the sleeve.

[0104] In some embodiments, the housing is cylindrical and the axis is a center axis.

[0105] In some embodiments, the handle assembly further comprises a bumper positioned to abut the plunger when the plunger is in the retracted position.

[0106] In some embodiments, the handle assembly further comprises a near field communication tag positioned within the housing.

[0107] In some embodiments, the sleeve and the plunger abut with a self-aligning interface.

[0108] Other aspects of the disclosure will become apparent by consideration of the detailed description and accompanying drawings.TAXA-44420601BRIEF DESCRIPTION OF THE DRAWINGS

[0109] These and other features, aspects, and advantages of the present technology will become better understood with regards to the following drawings. The accompanying figures and examples are provided by way of illustration and not by way of limitation.

[0110] FIG. 1 is a perspective view of an applicator system including a pod assembly and a handle assembly.

[0111] FIG. 2 is a perspective view of the applicator system of FIG. 1, illustrating the pod assembly removed from the handle assembly.

[0112] FIG. 3 is an exploded view of the pod assembly of FIG. 1.

[0113] FIG. 4 is a cross-section view of the pod assembly of FIG. 1, taken along the lines 4-4 shown in FIG. 2.

[0114] FIG. 5 is an exploded view of the handle assembly of FIG. 1.

[0115] FIG. 6 is a perspective cross-sectional view of the handle assembly of FIG. 1, taken along the lines 6-6 shown in FIG. 2.

[0116] FIG. 7A is a cross-sectional view of the applicator system of FIG. 1, shown in a first configuration with the pod assembly attached to the handle assembly, and a plunger of the handle assembly in a retracted position.10117] FIG. 7B is a cross-sectional view of the applicator sy stem of FIG. 1, show n in a second configuration with the pod assembly attached to the handle assembly, and the plunger of the handle assembly in an extended position.[0118| FIG. 7C is a cross-sectional view of the applicator system of FIG. 1, shown in a third configuration with the pod assembly removed from the handle assembly, and the plunger of the handle assembly in the retracted position.

[0119] FIG. 7D is a perspective cross-sectional view of the applicator system of FIG. 1, taken along the lines 7D-7D shown in FIG. 7 A.10120] FIG. 8 is a cross-sectional schematic of apod assembly.

[0121] FIG. 9 is a cross-sectional schematic of apod assembly.

[0122] FIG. 10 is a cross-sectional schematic of a pod assembly.

[0123] FIG. 11 A is a cross-sectional schematic of a pod assembly.TAXA-44420601[0124J FIG. 1 IB is a cross-sectional schematic of a pod assembly.[0125J FIG. 11C is a cross-sectional schematic of apod assembly.

[0126] FIG. 1 ID is a cross-sectional schematic of apod assembly.

[0127] FIG. 12A is a cross-sectional schematic of a pod assembly.

[0128] FIG. 12B is a cross-sectional schematic of a pod assembly.

[0129] FIG. 13A is a cross-sectional schematic of a pod assembly.

[0130] FIG. 13B is a cross-sectional schematic of a pod assembly.

[0131] FIG. 14A is a cross-sectional schematic of a pod assembly.|0132] FIG. 14B is a cross-sectional schematic of a pod assembly.10133] FIG. 15A is a cross-sectional schematic of a pod assembly.

[0134] FIG. 15B is a cross-sectional schematic of a pod assembly.

[0135] FIG. 15C is a cross-sectional schematic of a pod assembly.

[0136] FIG. 15D is a cross-sectional schematic of a pod assembly.[0137| FIG. 16 is a perspective view of an applicator system including a pod assembly and a handle assembly.

[0138] FIG. 17 is a perspective view of the applicator system of FIG. 16, illustrating the pod assembly removed from the handle assembly.

[0139] FIG. 18 is an exploded top perspective view of the pod assembly of FIG. 16.

[0140] FIG. 19 is an exploded bottom perspective view of the pod assembly of FIG. 16.

[0141] FIG. 20 is a cross-sectional exploded view of the pod assembly of FIG. 16.|0142] FIG. 21 is a cross-sectional view of the pod assembly of FIG. 16.10143] FIG. 22 is an exploded view of the handle assembly of FIG. 16.

[0144] FIG. 23 is a perspective cross-sectional view of the handle assembly of FIG. 16.

[0145] FIG. 24A is a cross-sectional view of the applicator system of FIG. 16, shown in a first configuration with the pod assembly attached to the handle assembly, and a plunger of the handle assembly in a retracted position.TAXA-44420601

[0146] FIG. 24B is a cross-sectional view of the applicator system of FIG. 16. shown in a second configuration with the pod assembly attached to the handle assembly, and the plunger of the handle assembly in an extended position.

[0147] FIG. 24C is a cross-sectional view of the applicator system of FIG. 16. shown in a third configuration with the pod assembly removed from the handle assembly, and the plunger of the handle assembly in the retracted position.

[0148] FIG. 25 is a bottom perspective view of the handle assembly of FIG. 16, with portions removed.

[0149] FIG. 26 is a graph illustrating total viable skin probiotic CFUs delivered from an extrusion device using tablets formulated with increasing mass fractions of lyophilized probiotic powder (0.1%, 1%, 10%, 90% w / w). Tablets of approximately 145mg containing lyophilized skin probiotic cells were extruded for approximately 1 second through approximately 1.2mL of aqueous solution. The extrudate was collected and resuspended in citrate-buffered saline (CBS; 1 *, pH 5.4), and viable counts were quantified by serial dilution and plating on TSA to back-calculate total CFUs extruded per sample. Plotted points are means across measurement replicates for each formulation and each plotted point represents one extrusion from one tablet; error bars represent ±1 standard error (log scale).

[0150] FIG. 27 is a graph illustrating that the lyophilized skin probiotic cells remain viable for at least 7 months. Viability was assessed on Day 0 (lyophilization day) and at 32, 115, and 209 days post-lyophilization. Lyophilized powder containing a benchmark skin probiotic strain of S. hominis originally isolated from the axilla of a human volunteer was reconstituted in PBS and plated on TSA, showing high viable counts at all time points with no discernible decrease from 32 to 209 days. Plotted points are means across replicate CFU plating experiments; error bars represent 2 standard deviations.DETAILED DESCRIPTION

[0151] Before any embodiments are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways.

[0152] Section headings as used in this section and the entire disclosure herein are merely for organizational purposes and are not intended to be limiting.TAXA-444206011. Definitions[0153J The singular forms “a” “an” and “the” include plural referents unless the context clearly dictates otherwise. Approximating language, as used herein throughout the specification and claims, may be applied to modify any quantitative representation that could permissibly vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term such as “about” or “approximately” is not to be limited to the precise value specified. Unless otherw ise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0154] For the recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the number 6.0, 6.1, 6.2, 6.3. 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated.

[0155] The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, e.g., elements that are conjunctively present in some cases and disjunctively present in other cases.10156] Use of ordinal terms such as “first,” “second.” “third.” etc., in the claims or specification to modify an element does not by itself connote any priority, precedence, or order of one claim element over another or the temporal order in which acts of a method are performed but are used merely as labels to distinguish one element having a certain name from another element having the same name.

[0157] The term “coupled,” as used herein, is defined as “connected,” although not necessarily directly, and not necessarily mechanically. The term coupled is to be understood to mean physically, magnetically, chemically, electrically, or otherwise coupled, connected or linked and does not exclude the presence of intermediate elements between the coupled elements absent specific contrary' language.TAXA-44420601

[0158] The term “configured to” describes hardware, software or a combination of hardware and software that is adapted to, set up. arranged, commanded, altered, modified, built, composed, constructed, designed, or that has any combination of these characteristics to carry out a given function.

[0159] “Subject” as used herein is any mammalian or non-mammalian subject. In some embodiments, the subject is a human subject. In some embodiments, the subject has, or is at risk of having, body odor.

[0160] As used herein, “apply,” “applying,” or “applied” refers to introducing or delivering to a subject an agent, drug, bacterial strain (e.g., probiotic) or spore thereof, or compound, individually or part of a composition, to perform its intended function, and includes topical administration.

[0161] As used herein, the term “effective amount” refers to a quantity, concentration, level, or amount sufficient to achieve a desired therapeutic and / or prophylactic effect (e.g., an amount which results in the prevention or treatment of a condition, and / or symptom(s) thereof). In the context of therapeutic or prophylactic applications, the amount of an agent or composition administered to a subject will depend on the type and severity of the condition and on the characteristics of the subject, such as general health, age, sex, body weight, and lifestyle. It w ill also depend on the degree, severity, and type of condition. In some embodiments, an effective amount of a composition may include levels at which the presence, frequency, or severity of body odor (or a related symptom thereof) is ameliorated or eliminated in the subject. In some embodiments, an effective amount reduces or ameliorates the presence of body odor, and / or the likelihood of developing body odor (or a related symptom thereof). In some embodiments, an effective amount is achieved by applying a single dose. In some embodiments, an effective amount is achieved by applying multiple doses.

[0162] The terms “engineered” or “genetically engineered” as used herein generally refers to an organism whose genome has been genetically altered, modified, or changed (e.g., by the addition, removal, and / or editing of one or more nucleotides in the genome). For example, an engineered or genetically engineered bacterial strain encompasses a bacterial strain that has had one or more nucleotides added, removed, or changed with respect to its natural (unaltered) genome.TAXA-44420601[0163J The terms “probiotic’' and “probiotic composition’" generally refer to any bacterium, or a composition that contains any bacterium, which confers a beneficial effect when administered to a subject. In some embodiments, the probiotic and probiotic compositions of the present disclosure include at least one probiotic (e.g., one type or strain of bacterium). In other embodiments, the probiotic and probiotic compositions of the present disclosure include more than one probiotic (e.g., more than one type or strain of bacterium). As described further herein, the probiotic and probiotic compositions of the present disclosure can include a “skin probiotic,” which generally refers to any skin bacterium that confers a beneficial effect when administered to a subject (e.g., topically administered to the skin of a subject). In some embodiments, administration of a skin probiotic or skin probiotic composition to a subject results in the supplementation and / or replacement of elements of the endogenous flora (i.e., skin microbiome) of the subject, which can confer a beneficial prophylactic and / or therapeutic effect on the subject. For example, in some embodiments, the beneficial effect is a reduction or prevention in malodor on the skin of a subject. As would be appreciated by one of ordinary skill in the art based on the present disclosure, a skin probiotic can be obtained or derived from the skin microbiome of a subject, which generally includes several species of bacteria.[0164| The term “tablet” as used herein, generally refers to a compressed solid substance. A tablet may be in the shape of a disk, cylinder, or any other suitable shape.

[0165] In the foregoing description, specific terminology has been resorted to for the sake of clarity. However, the invention is not intended to be limited to the specific terms so selected, and it is to be understood that each specific term includes all technical equivalents which operate in a similar manner to accomplish a similar technical purpose. Terms such as “top” and “bottom”, “front” and “rear”, “inner” and “outer”, “above”, “below”, “upper”, “lower”, “vertical”, “horizontal”, “upright” and the like are used as words of convenience to provide reference points.2. Systems Overview

[0166] With reference to FIGS. 1 and 2, a system 10 includes a handle assembly 14 and a pod assembly 18. As detailed further herein, the handle assembly 14 includes a plunger 154 movable in response to user actuation of an actuator 158. The pod assembly 18 is removably coupled to the handle assembly 14. As detailed further herein, the pod assembly 18 includes an outlet 26 and a skin probiotic or probiotic composition 38 and a fluid 42. The composition 38 and the fluid 42 are dispensed from the outlet 26 for application to skin, for example, inTAXA-44420601response to user actuation of the actuator 158. The pod assembly 18 is removably coupled to the handle assembly 14 such that the pod assembly 18 may be a single-use disposable while the handle assembly 14 may be reused with additional pod assemblies.

[0167] With reference to FIGS. 16 and 17, a system 310 includes a handle assembly 314 and a pod assembly 318. As detailed further herein, the handle assembly 314 includes a plunger 322 movable in response to user actuation of an actuator 326. The pod assembly 318 is removably coupled to the handle assembly 314. As detailed further herein, the pod assembly 318 includes a housing 330 with an outlet 334, a composition 338, and a fluid 342. The composition 338 and the fluid 342 are dispensed from the outlet 334 for application to skin, for example, in response to user actuation of the actuator 326. The pod assembly 318 is removably coupled to the handle assembly 314 such that the pod assembly 318 may be a single-use disposable while the handle assembly 314 may be reused with additional pod assemblies.3. Pod Assemblies

[0168] With reference to FIGS. 3 and 4, the pod assembly 18 includes a housing 22 with an outlet 26, a first cartridge 30 positioned within the housing 22, and a second cartridge 34 positioned within the housing 22. In the illustrated embodiment, the first cartridge 30 is positioned between the outlet 26 and the second cartridge 34. The first cartridge 30 includes a composition 38. The second cartridge 34 includes a fluid 42. As detailed herein, the pod assembly 18 is movable between a first configuration (FIG. 7A) and a second configuration (FIG. 7B). In the first configuration, the first cartridge 30 and the second cartridge 34 are sealed and separated. In the second configuration, the first cartridge 30 and the second cartridge 34 are opened such that the composition 38 and the fluid 42 are dispensed through the outlet 26.

[0169] In some embodiments, the composition 38 is at least one skin probiotic. In some embodiments, the at least one skin probiotic 38 is genetically engineered. In some embodiments, the skin probiotic 38 comprises a Staphylococcus strain, aCutibacterium strain, a Corynebacterium strain, a Bacillus strain, a Micrococcus strain, and / or a Lactobacillus strain. In some embodiments, the skin probiotic 38 comprises a Coagulasenegative Staphylococci (CoNS). In some embodiments, the skin probiotic 38 comprises one or more of S. hominis, S. lugdunensis, S. haemolyticus, S. epidermidis, and / or S. cohnii.TAXA-44420601[0170J In some embodiments, the skin probiotic 38 is genetically engineered to comprise a disruption in at least one endogenous gene. In some embodiments, the skin probiotic 38 comprises a Staphylococcus hominis strain having a disrupted patB gene. In some embodiments, the skin probiotic 38 comprises a Staphylococcus hominis strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof. In some embodiments, the skin probiotic 38 comprises a Staphylococcus lugdunensis strain having a disrupted patB gene. In some embodiments, the skin probiotic 38 comprises a Staphylococcus lugdunensis strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof.

[0171] Examples of such skin probiotics are disclosed in PCT Patent Application No. PCT / US2024 / 028188, which is incorporated herein by reference in its entirety7. In some embodiments, the skin probiotic 38 is formulated as a desiccated skin probiotic powder.

[0172] In some embodiments, the fluid 42 is a water-based fluid sufficient to re-hydrate the desiccated skin probiotic 38. In some embodiments, the fluid 42 is an aqueous solution, an aqueous gel, an aqueous cream, or a combination thereof. In some embodiments, the water-based fluid includes silk peptides, xanthan gum, diutan gum, hyaluronic acid, or any combination thereof, which are substantially dissolved within the fluid 42. The fluid 42 is preservative free such that the fluid 42 does not negatively affect the viability of the skin probiotic 38 when combined with the skin probiotic 38. In some embodiments, the second cartridge 34 including the fluid 42 is sterilized because the fluid 42 is preservative free. In one example, the second cartridge 34 is gamma irradiated. In one example, the second cartridge 34 is electron beam irradiated. In other embodiments, sterilization of the second cartridge 34 is achieved with heat or other suitable methods of sanitation. Advantageously, the second cartridge 34 is separate from the first cartridge 30 allowing the second cartridge 34 to be sterilized while the first cartridge 30 is not subject to sterilization. Advantageously, the first cartridge 30 and the second cartridge 34 are sealed, do not mix during storage or transport of the pod assembly 18, and are shelf stable.

[0173] With continued reference to FIGS. 3 and 4, the pod assembly 18 further includes a puncture member 46 positioned within the housing 22. In the illustrated embodiment, the puncture member 46 is positioned between the first cartridge 30 and the second cartridge 34. The puncture member 46 has a first side 50 in facing relationship with the first cartridge 30 and a second side 54, opposite the first side 50, in facing relationship with the second cartridge 34. In the illustrated embodiment, the puncture member 46 includes a plurality ofTAXA-44420601first piercing elements 58 positioned on the first side 50 configured to open the first cartridge 30, and a plurality of second piercing elements 62 positioned on the second side 54 configured to open the second cartridge 34. In the illustrated embodiment, the puncture member 46 includes a center opening 66, and a plurality of openings 70 that extend through the piercing elements 58, 62. As detailed further herein, the center opening 66 and the plurality of openings 70 of the puncture member 46 are configured to receive the fluid 42 in the second configuration of the pod assembly 18. In other words, the fluid 42 travels through the openings 66, 70 in the puncture member 46 after the piercing elements 62 pierces through and opens the second cartridge 34.

[0174] With reference to FIG. 4, in the illustrated embodiment, the first cartridge 30 includes a first cartridge housing 74, a first seal 78 coupled to the first cartridge housing 74, and a second seal 82 coupled to the first cartridge housing 74. In the illustrated embodiment, the first cartridge housing 74 includes a first aperture 86 at a first end 90 and a second aperture 94 at a second end 98, opposite the first end 90. In the first configuration, the first seal 78 covers the first aperture 86 and the second seal 82 covers the second aperture 94. In the second configuration, the first seal 78 and the second seal 82 are broken. In other words, the first cartridge 30 is sealed in the first configuration of the pod assembly 18. and the first cartridge 30 is opened in the second configuration of the pod assembly 18.

[0175] With continued reference to FIG. 4, in the illustrated embodiment, the second cartridge 34 includes a second cartridge housing 102 and a first seal 106 coupled to the second cartridge housing 102. In the illustrated embodiment, the second cartridge housing 102 includes a first aperture 110, and the first seal 106 covers the first aperture 110 in the first configuration. In the second configuration, the first seal 106 is broken. In the illustrated embodiment, in the second configuration, the second cartridge 34 moves with respect to the housing 22 to cause the puncture member 46 to abut the second cartridge 34 and the first cartridge 30, thereby opening the second cartridge 34 and the first cartridge 30. In other words, the second cartridge 34 translates towards the puncture member 46 and brings the puncture member 46 into contact with both the first cartridge 30 and the second cartridge 34.|0176] In the illustrated embodiment, the first cartridge 30 and the second cartridge 34 are positioned within a channel 24 of the housing 22 and are movable with respect to the housing 22 along a pod axis 25. In the illustrated embodiment, the first cartridge 30 and the second cartridge 34 abut the channel 24. In the illustrated embodiment, the composition 38 is positioned within the first cartridge 30 and positioned within the housing 22. In theTAXA-44420601illustrated embodiment, the fluid 42 is positioned within the second cartridge 34 and positioned within the housing 22. In the illustrated embodiment, the first cartridge 30 is positioned between the outlet 26 and the second cartridge 34. In other words, the composition 38 is positioned between the fluid 42 and the outlet 26 in the first configuration.

[0177] In the illustrated embodiment, the pod axis 25 intersects the first cartridge 30 and the second cartridge 34. As detailed further herein, the second cartridge 34 is driven towards the first cartridge 30 and the outlet 26 along the pod axis 25 by the handle assembly 14. When the pod assembly 18 is in the second configuration, a water-based fluid 42 carries the skin probiotic 38 through the outlet 26 and re-hydrates the skin probiotic 38. In the illustrated embodiment, the outlet 26 is at a first end 114 of the housing 22. In some embodiments, the pod assembly 18 includes any number of outlets 26 formed at the first end 114 of the housing 22. In the illustrated embodiment, the outlet 26 is partially formed by a stem 118 with a piercing end 122 and a plurality of apertures 126. The piercing end 122 of the stem 118 is configured to pierce the first seal 78 of the first cartridge 30, and the plurality of apertures 126 are configured to allow for the flow7and dispensing of the composition 38 and the fluid 42 through the outlet 26. In some embodiments, in the second configuration, the fluid 42 pushes at least a portion of the skin probiotic 38 through the outlet 26 and re-hydrates the skin probiotic 38.

[0178] The housing 22 further includes a connector 130 at a second end 134 of the housing 22, opposite the first end 114. The second end 134 of the housing 22 includes an opening 138 and the second cartridge 34 is positioned within the opening 138. In other words, the second cartridge 34 is exposed at the opening 138 in the housing 22. In the illustrated embodiment, the opening 138 is configured to receive a plunger (e.g., the plunger 154).

[0179] With reference to FIGS. 18-21, the pod assembly 318 includes the housing 330 with the outlet 334, the composition 338, and the fluid 342. In the illustrated embodiment, the fluid 342 is positioned within a fluid cartridge 346 and the composition 338 is in a tablet form and positioned within the housing 330. As detailed herein, the pod assembly 318 is movable between a first configuration (FIG. 24A) and a second configuration (FIG. 24B). The composition 338 and the fluid 342 are separated in the first configuration. The composition 338 and the fluid 342 are at least partially combined and dispensed through the outlet 334 in the second configuration. In some embodiments, a removable seal 344 isTAXA-44420601positioned over the outlet 334 during storage and the seal 344 is removed by a user when the pod assembly 318 is ready for use.

[0180] In some embodiments, the composition 338 is at least one skin probiotic. In some embodiments, the at least one skin probiotic 338 is genetically engineered. In some embodiments, the skin probiotic 338 comprises a Staphylococcus strain, a Cutihacterium strain, a C orynebacterium strain, a Bacillus strain, aMicrococcus strain, and / or a Lactobacillus strain. In some embodiments, the skin probiotic 338 comprises a Coagulasenegative Staphylococci (CoNS). In some embodiments, the skin probiotic 338 comprises one or more of S. hominis, S. lugdunensis, S. haemolyticus, S. epidermidis, and / or S. cohnii.[0181| In some embodiments, the skin probiotic 338 is genetically engineered to comprise a disruption in at least one endogenous gene. In some embodiments, the skin probiotic 338 comprises a Staphylococcus hominis strain having a disrupted patB gene. In some embodiments, the skin probiotic 338 comprises a Staphylococcus hominis strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof. In some embodiments, the skin probiotic 338 comprises a Staphylococcus lugdunensis strain having a disrupted patB gene. In some embodiments, the skin probiotic 338 comprises a Staphylococcus lugdunensis strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof.

[0182] Examples of such skin probiotics are disclosed in PCT Patent Application No. PCT / US2024 / 028188, which is incorporated herein by reference in its entirety. In some embodiments, the skin probiotic 338 is formed as a tablet.10183] In the illustrated embodiment, the composition 338 is formed as a tablet.Advantageously, the tablet form may provide cost of manufacturing benefits, while the composition 338 remains viable and capable of being transported and engrafted.

[0184] In some embodiments, the fluid 342 is a water-based fluid. In some embodiments, the water-based fluid 342 is an aqueous solution, an aqueous gel, an aqueous cream, or a combination thereof. In some embodiments, the water-based fluid 342 includes silk peptides, xanthan gum, diutan gum, hyaluronic acid, or any combination thereof, which are substantially dissolved within the fluid. In some embodiments, the fluid 342 is a lipid-based component. In some embodiments, the fluid 342 is a non-polar emollient component. In some embodiments, the fluid 342 is preservative free such that the fluid 342 does not negatively affect the viability of the skin probiotic 338 when combined with the skinTAXA-44420601probiotic 338. In some embodiments, the fluid 342 is sterilized because the fluid 342 is preservative free. In one example, the fluid 342 is gamma irradiated. In one example, the fluid 342 is electron beam irradiated. In other embodiments, sterilization of the fluid 342 is achieved with heat or other suitable methods of sanitation. Advantageously, the fluid 342 is separate from the skin probiotic 338 allowing the fluid 342 to be sterilized while the skin probiotic 338 is not subject to sterilization. In other embodiments, the fluid 342 includes a preservative, for example, dehydroacetic acid (DHA) and salts including sodium dehydroacetate, sodium benzoate, aspen bark extract, radish root ferment, potassium sorbate, capryloyl glycine, or any other suitable preservative. Advantageously, the skin probiotic 338 and the fluid 342 are separated, do not mix during storage or transport of the pod assembly 318, and are shelf stable.

[0185] With continued reference to FIGS. 20 and 21, the pod assembly 318 further includes a puncture member 350 positioned within the housing 330. In the illustrated embodiment, the puncture member 350 is partially received within a bore 354 formed in the housing 330. In the illustrated embodiment, the outlet 334 of the housing 330 is in fluid communication with the bore 354. The puncture member 350 has a first side 358 in facing relationship with the outlet 334 and a second side 362, opposite the first side 358, in facing relationship with the fluid cartridge 346. The first side 358 is partially positioned within the bore 354. In the illustrated embodiment, the puncture member 350 includes a plurality of piercing elements 366 positioned on the second side 362 configured to open the fluid cartridge 346.10186] With continued reference to FIGS. 19-21. the puncture member 350 includes a cavity 370 and at least one retaining rib 374 extending into the cavity 370. In the illustrated embodiment, the at least one retaining rib 374 extends radially inward from an inner surface 378 of the cavity 370. In the illustrated embodiment, the composition 338 tablet is at least partially positioned within the puncture member 350 in the first configuration. The at least one retaining rib 374 is configured to secure the composition 338 tablet within the cavity 370. In the illustrated embodiment, the puncture member 350 includes an opening 382, and a plurality of channels 386 that extend along the cavity 370. As detailed further herein, the channels 386 of the puncture member 350 are configured to receive the fluid 342 in the second configuration of the pod assembly 318. In other words, the fluid 342 travels through the puncture member 350 after the piercing elements 366 pierces through and open the fluid cartridge 346.TAXA-44420601[0187J With reference to FIGS. 20 and 21, in the illustrated embodiment, the fluid cartridge 346 includes a cartridge housing 390 and a seal 394 coupled to the cartridge housing 390. In the illustrated embodiment, the cartridge housing 390 includes an aperture 398, and the seal 394 covers the aperture 398 in the first configuration. In the illustrated embodiment, the cartridge housing 390 includes a recess 402 formed in a bottom surface 406, which is configured to receive a plunger (e.g., the plunger 322). In the second configuration, the seal 394 is broken. In the illustrated embodiment, in the second configuration, the fluid cartridge 346 moves with respect to the housing 330 to abut the puncture member 350, thereby opening the fluid cartridge 346. In other words, the fluid cartridge 346 translates towards the puncture member 350 and the composition 338 tablet in response to external force applied at, for example, the recess 402.

[0188] In the illustrated embodiment, the fluid cartridge 346 is positioned within a channel 410 of the housing 330 and is movable with respect to the housing 330 along a pod axis 414. A first sealing member 418 is positioned between the fluid cartridge 346 and the housing 330. In some embodiments, the fluid cartridge 346 abuts the channel 410. In the illustrated embodiment, a second sealing member 422 is positioned between the puncture member 350 and the housing 330. In some embodiments, the first sealing member and the second sealing member are O-rings. In some embodiments, the first sealing member or the second sealing member is a rubberized sealing film. In the illustrated embodiment, the composition 338 is positioned within the puncture member 350 and positioned within the housing 330. In the illustrated embodiment, the fluid 342 is positioned within the fluid cartridge 346 and positioned within the housing 330. In the illustrated embodiment, the composition 338 is positioned between the fluid 342 and the outlet 334 in the first configuration.

[0189] In the illustrated embodiment, the pod axis 414 intersects the composition 338 tablet and the fluid cartridge 346. As detailed further herein, the fluid cartridge 346 is driven towards the composition 338 and the outlet 334 along the pod axis 414 by the handle assembly 314. When the pod assembly 318 is in the second configuration, the fluid 342 carries the composition 338 through the outlet 334 and re-hydrates the composition 338. In the illustrated embodiment, the outlet 334 is at a first end 426 of the housing 330. In some embodiments, the pod assembly 318 includes any number of outlets 334 formed at the first end 426 of the housing 330. In the illustrated embodiment, the outlet 334 is partially formed by a stem 430 with a plurality of apertures 434. The puncture member 350 is at least partially positioned within the stem 430. The plurality of apertures 434 formed in the stem 430 areTAXA-44420601configured to allow for the flow and dispensing of the composition 338 and the fluid 342 through the outlet 334. In some embodiments, in the second configuration, the fluid 342 pushes at least a portion of the skin probiotic 338 tablet through the outlet 334 and rehydrates the skin probiotic 338.

[0190] In the illustrated embodiment, the housing 330 includes an upper body 438 and a lower body 442. The outlet 334 is formed in the upper body 438. The lower body 442 includes a window 446 (FIG. 21) to receive a pip 450 formed on the upper body 438. The housing 330 further includes a connector 454 at a second end 458 of the housing 330, opposite the first end 426. The second end 458 of the housing 330 includes an opening 462 and the fluid cartridge 346 is positioned at least partially within the opening 462. In other words, the fluid cartridge 346 is exposed at the opening 462 in the housing 330. In the illustrated embodiment, the opening 462 is configured to receive a plunger (e.g., the plunger 322). In the illustrated embodiment, the opening 462 is formed in the lower body 442 such that the fluid cartridge 346 is mechanically accessible through the opening 462.

[0191] With references to FIGS. 8-15D, pod assemblies are illustrated with various arrangements of a fluid 504 and a composition 508.

[0192] With reference to FIG. 8, a pod assembly 512 is illustrated in a first configuration. The pod assembly 512 includes a housing 516 w ith an outlet 520, a first cartridge 524 includes the composition 508, and a second cartridge 528 includes the fluid 504. The second cartridge 528 is positioned between the outlet 520 and the first cartridge 524 in the first configuration. In other words, the fluid 504 is positioned between the outlet 520 and the composition 508 in the first configuration. In the illustrated embodiment, the first cartridge 524 and the second cartridge 528 are spaced from an internal sidewall 532 of the housing 516. In the illustrated embodiment, moving the pod assembly 512 from the first configuration to the second configuration causes the composition 508 to move toward the fluid 504 and to at least partially combine with the fluid 504.

[0193] With reference to FIG. 9, a pod assembly 536 is illustrated in a first configuration. The pod assembly 536 includes a housing 540 with an outlet 544, a first cartridge 548 includes the composition 508, and a second cartridge 552 includes the fluid 504. In the illustrated embodiment, the first cartridge 548 and the second cartridge 552 are positioned side-by-side. The composition 508 is positioned a first distance 556 from the outlet 544 in the first configuration, and the fluid 504 is positioned a second distance 560 from the outletTAXA-44420601544 in the first configuration. In some embodiments, the first distance 556 is equal to the second distance 560. In some embodiments, the first distance is different than the second distance. In the illustrated embodiment, moving the pod assembly 536 from the first configuration to the second configuration causes the composition 508 and the fluid 504 to move toward a mixing zone 564 where the composition 508 and the fluid 504 are at least partially combined.

[0194] With reference to FIG. 10, a pod assembly 568 is illustrated in a first configuration. The pod assembly 568 includes a housing 572 with an outlet 576 and the fluid 504 is positioned within a chamber 580 at least partially defined by the housing 572. The composition 508 is formed as a tablet and positioned within the housing 572. The pod assembly 568 includes a separator 584 that separates the fluid 504 from the composition 508. In some embodiments, the separator 584 is a frangible seal (e g., a foil seal).

[0195] With reference to FIG. 11 A, a pod assembly 588 is illustrated in a first configuration. The pod assembly 588 includes a housing 592 with an outlet 596. a first cartridge 600 includes the composition 508, and a second cartridge 604 includes the fluid 504. In the illustrated embodiment, w all portions 608 form part of the housing 592 and part of the first cartridge 600. In the illustrated embodiment, w all portions 612 form part of the housing 592 and part of the second cartridge 604. In the illustrated embodiment, the first cartridge 600 is spaced from the second cartridge 604. In the illustrated embodiment, the second cartridge 604 is positioned between the outlet 596 and the first cartridge 600.

[0196] With reference to FIG. 1 IB, a pod assembly 616 is illustrated in a first configuration. The pod assembly 616 includes a housing 620 with an outlet 624, a first cartridge 628 includes the composition 508, and a second cartridge 632 includes the fluid 504. In the illustrated embodiment, wall portions 636 form part of the housing 620 and part of the first cartridge 628. In the illustrated embodiment, wall portions 640 form part of the housing 620 and part of the second cartridge 632. In the illustrated embodiment, the first cartridge 628 is spaced from the second cartridge 632. In the illustrated embodiment, the first cartridge 628 is positioned between the outlet 624 and the second cartridge 632.

[0197] With reference to FIG. 11C, a pod assembly 644 is illustrated in a first configuration. The pod assembly 644 includes a housing 648 with an outlet 652, a first cartridge 656 includes the composition 508, and a second cartridge 660 includes the fluid 504. In the illustrated embodiment, wall portions 664 form part of the housing 648 and partTAXA-44420601of the first cartridge 656. In the illustrated embodiment, wall portions 668 form part of the housing 648 and part of the second cartridge 660. In the illustrated embodiment, a wall portion 672 forms part of both the first cartridge 656 and the second cartridge 660. In other words, the first cartridge 656 and the second cartridge 660 share the common wall portion 672. In the illustrated embodiment, the second cartridge 660 is positioned between the outlet 652 and the first cartridge 656.

[0198] With reference to FIG. 1 ID, a pod assembly 676 is illustrated in a first configuration. The pod assembly 676 includes a housing 680 with an outlet 684. a first cartridge 688 includes the composition 508, and a second cartridge 692 includes the fluid 504. In the illustrated embodiment, w all portions 696 form part of the housing 680 and part of the first cartridge 688. In the illustrated embodiment, w all portions 700 form part of the housing 680 and part of the second cartridge 692. In the illustrated embodiment, a wall portion 704 forms part of both the first cartridge 688 and the second cartridge 692. In other w ords, the first cartridge 688 and the second cartridge 692 share the common wall portion 704. In the illustrated embodiment, the first cartridge 688 is positioned between the outlet 684 and the second cartridge 692. As illustrated herein, the cartridges may have various boundaries in various embodiments.

[0199] With reference to FIG. 12A, a pod assembly 708 is illustrated in a first configuration. The pod assembly 708 includes a housing 712 with an outlet 716, a first cartridge 720 includes the composition 508, and a second cartridge 724 includes the fluid 504. In the illustrated embodiment, the first cartridge 720 and the second cartridge 724 are positioned outside of the housing 712 in the first configuration. The second cartridge 724 is positioned between the housing 712 and the first cartridge 720 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 712 and the outlet 716 upon the pod assembly 708 moving to the second configuration.

[0200] With reference to FIG. 12B, a pod assembly 728 is illustrated in a first configuration. The pod assembly 728 includes a housing 732 with an outlet 736, a first cartridge 740 includes the composition 508, and a second cartridge 744 includes the fluid 504. In the illustrated embodiment, the first cartridge 740 and the second cartridge 744 are positioned outside of the housing 732 in the first configuration. The first cartridge 740 is positioned between the housing 732 and the second cartridge 744 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluidTAXA-44420601communication with the housing 732 and the outlet 736 upon the pod assembly 728 moving to the second configuration. As illustrated herein, the first cartridge and the second cartridge may be positioned outside of the housing in at least a first configuration of the pod assembly.

[0201] With reference to FIG. 13 A, a pod assembly 748 is illustrated in a first configuration. The pod assembly 748 includes a housing 752 with an outlet 756, a first cartridge 760 includes the composition 508, and a second cartridge 764 includes the fluid 504. In the illustrated embodiment, the first cartridge 760 is positioned outside the housing 752 in the first configuration, and the second cartridge 764 is positioned inside the housing 752 in the first configuration. The second cartridge 764 is positioned between the outlet 756 and the first cartridge 760 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 752 and the outlet 756 upon the pod assembly 748 moving to the second configuration.

[0202] With reference to FIG. 13B, a pod assembly 768 is illustrated in a first configuration. The pod assembly 768 includes a housing 772 with an outlet 776. a first cartridge 780 includes the composition 508, and a second cartridge 784 includes the fluid 504. In the illustrated embodiment, the second cartridge 784 is positioned outside of the housing 772 in the first configuration, and the first cartridge 780 is positioned inside the housing 772. The first cartridge 780 is positioned between the outlet 776 and the second cartridge 784 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 772 and the outlet 776 upon the pod assembly 768 moving to the second configuration. As illustrated herein, one of the cartridges may be positioned outside of the housing and the other of the cartridges may be positioned inside of the housing in at least a first configuration.

[0203] With reference to FIG. 14A, a pod assembly 788 is illustrated in a first configuration. The pod assembly 788 includes a housing 792 with an outlet 796, a first cartridge 800 includes the composition 508, and a second cartridge 804 includes the fluid 504. In the illustrated embodiment, the first cartridge 800 and the second cartridge 804 are positioned outside of the housing 792 in the first configuration. The first cartridge 800 is positioned within the second cartridge 804 in the first configuration. In the illustrated embodiment, the composition 508 is at least partially surrounded by the fluid 504 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 792 and the outlet 796 upon the pod assembly 788 moving to the second configuration.TAXA-44420601[0204J With reference to FIG. 14B, a pod assembly 808 is illustrated in a first configuration. The pod assembly 808 includes a housing 812 with an outlet 816. a first cartridge 820 includes the composition 508, and a second cartridge 824 includes the fluid 504. In the illustrated embodiment, the first cartridge 820 and the second cartridge 824 are positioned outside the housing 812 in the first configuration. The second cartridge 824 is positioned within the first cartridge 820 in the first configuration. In the illustrated embodiment, the fluid 504 is at least partially surrounded by the composition 508 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 812 and the outlet 816 upon the pod assembly 808 moving to the second configuration. As illustrated herein, one of the cartridges may be positioned within the other of the cartridges in the first configuration.

[0205] With reference to FIG. 15 A, the pod assembly 828 is illustrated in a first configuration. The pod assembly 828 includes a housing 832 with an outlet 836, the fluid 504 is positioned anywhere within the housing 832, and a cartridge 840 includes the composition 508. In the illustrated embodiment, the cartridge 840 is positioned outside the housing 832 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 832 and the outlet 836 upon the pod assembly 828 moving to the second configuration.

[0206] With reference to FIG. 15B, the pod assembly 844 is illustrated in a first configuration. The pod assembly 844 includes a housing 848 with an outlet 852, the composition 508 is positioned anywhere within the housing 848, and a cartridge 856 includes the fluid 504. In the illustrated embodiment, the cartridge 856 is positioned outside the housing 848 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 848 and the outlet 852 upon the pod assembly 844 moving to the second configuration.

[0207] With reference to FIG. 15C, the pod assembly 860 is illustrated in a first configuration. The pod assembly 860 includes a housing 864 with an outlet 868, the fluid 504 is positioned anywhere within the housing 864, and a cartridge 872 includes the composition 508. In the illustrated embodiment, the cartridge 872 is positioned inside the housing 864 in the first configuration. In some embodiments, the composition 508 is at least partially surrounded by the fluid 504 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 864 and the outlet 868 upon the pod assembly 860 moving to the second configuration.TAXA-44420601[0208J With reference to FIG. 15D, the pod assembly 876 is illustrated in a first configuration. The pod assembly 876 includes a housing 880 with an outlet 884. the composition 508 is positioned anywhere within the housing 880, and a cartridge 888 includes the fluid 504. In the illustrated embodiment, the cartridge 888 is positioned inside the housing 880 in the first configuration. In some embodiments, the fluid 504 is at least partially surrounded by the composition 508 in the first configuration. In the illustrated embodiment, the composition 508 and the fluid 504 are placed in fluid communication with the housing 880 and the outlet 884 upon the pod assembly 876 moving to the second configuration.4. Handle Assembly

[0209] With reference to FIGS. 5 and 6, the handle assembly 14 includes a housing 142, a pressure body 146 movable with respect to the housing 142, a sleeve 150, a plunger 154, and an actuator 158. In the illustrated embodiment, the handle assembly 14 further includes a first spring 162 positioned between the pressure body 146 and the sleeve 150, and a second spring 166 positioned between the plunger 154 and the sleeve 150. The handle assembly 14 includes at least one spring that biases the pressure body 146. The housing 142 defines an axis 170. In the illustrated embodiment, the housing 142 is cylindrical and the axis 170 is a center axis. In other embodiments, the housing 142 may be any suitable shape.

[0210] The pressure body 146 moves with respect to the housing 142 betw een a first position (FIG. 7C) and a second position (FIGS. 7A and 7B). In the illustrated embodiment, the pressure body 146 moves with respect to the housing 142 along the axis 170 between the first position when the pod assembly 18 is detached from the handle assembly 14 and the second position when the pod assembly 18 is attached to the handle assembly 14. The pressure body 146 includes an end w all 174 and a side wall 178. An opening 182 is formed in the end wall 174 and a bore 186 is formed by the side wall 178 and the end wall 174. As detailed herein, the plunger 154 extends through the opening 182 of the pressure body 146.

[0211] With continued reference to FIGS. 5 and 6, the first spring 162 biases the pressure body 146 to the first position. In the illustrated embodiment, the first spring 162 biases the pressure body 146 aw ay from the sleeve 150. In the illustrated embodiment, the first spring 162 is positioned w ithin the bore 186. A first end 190 of the first spring 162 abuts the end wall 174 of the pressure body 146, and a second end 194 of the first spring 162 abuts an end surface 198 of the sleeve 150. As such, when the pod assembly 18 is attached to the handleTAXA-44420601assembly 14, the pod assembly 18 moves the pressure body 146 to the second position, against the bias of the first spring 162. When the pod assembly 18 is removed from the handle assembly 14, the first spring 162 returns the pressure body 146 to the first position.

[0212] With continued reference to FIGS. 5 and 6. the handle assembly 14 further includes at least one aperture 202 formed in the sleeve 150, and at least one ball 206 positioned in the aperture 202. In the illustrated embodiment, the handle assembly 14 includes four apertures 202 and four balls 206, with one ball corresponding to each aperture. In other embodiments, any number of balls and apertures in the sleeve may be utilized. The balls 206 may be referred to as ball bearings or spheres.[0213| In the illustrated embodiment, the sleeve 150 is stationary relative to the housing 142. The sleeve 150 includes a first cylindrical wall portion 210, a second cylindrical wall portion 214, and a ledge 218 extending between the first cylindrical wall portion 210 and the second cylindrical wall portion 214. The apertures 202 are formed in the first cylindrical wall portion 210. In the illustrated embodiment, the first cylindrical wall portion 210 has a smaller diameter than the second cylindrical wall portion 214.

[0214] The second spring 166 biases the plunger 154 to a retracted position. In the illustrated embodiment, the second spring 166 is positioned within a bore 222 formed by the second cylindrical wall portion 214. A first end 226 of the second spring 166 abuts the ledge 218, and a second end 230 of the second spring 166 abuts a flange 234 formed on the plunger 154.

[0215] With continued reference to FIGS. 5 and 6, the plunger 154 has an outer surface 238 with at least one helical groove 242. In the illustrated embodiment, a plurality of helical grooves 242 is formed in the outer surface 238 of the plunger 154 (e g., one helical groove 242 for each of the balls 206 included in the handle assembly 14). Each helical groove 242 is configured to receive the corresponding ball 206 when the pressure body 146 is in the second position. In other words, the ball 206 is positioned outside the helical groove 242 when the pressure body 146 is in the first position, and the pressure body 146 retains the ball 206 within the helical groove 242 when the pressure body' 146 is in the second position. In the illustrated embodiment, the side wall 178 of the pressure body 146 includes a contact surface 246 configured to abut the ball 206. In the illustrated embodiment, the contact surface 246 is beveled to cause radially inward motion of the ball 206 as the pressure body 146 moves along the axis 170 to the second position.TAXA-44420601

[0216] With continued reference to FIGS. 5 and 6, the actuator 158 includes a stem 250 coupled to the plunger 154 for co-rotation with the plunger 154 about the axis 170. In the illustrated embodiment, the stem 250 is non-circular. In the illustrated embodiment, the actuator 158 includes a graspable portion 254 with knurling. With reference to FIG. 7D, the actuator 158 is only permitted to rotate about the axis 170 in one direction. A pawl 258 positioned on the sleeve 150 interfaces with a plurality of teeth 262 formed on an inner surface 264 of the graspable portion 254 to permit one way rotation and to advantageously prevent the plunger 154 from being back driven when the plunger 154 is extended. In other words, the plunger 154 advantageously holds its position when extended and while the pod assembly 18 remains attached.

[0217] In operation, the plunger 154 moves with respect to the housing 142 along the axis 170 to an extended position (FIG. 7B) in response to rotation of the actuator 158 about the axis 170 when the pressure body 146 is in the second position. In other words, when the pressure body 146 is in the second position, the plunger 154 translates along the axis 170 relative to the stem 250 in response to the stem 250 and the plunger 154 co-rotating about the axis 170. Advantageously, the plunger 154 does not translate along the axis 170 in response to actuation of the actuator 158 when the pressure body 146 is in the first position. In other words, the plunger 154 will not extend in response to user actuation of the actuator 158 when there is no pod assembly 18 attached to the handle assembly 14.

[0218] As discussed in further detail herein, the plunger 154 of the handle assembly 14 automatically retracts from the extended position to the retracted position in response to the pod assembly 18 being removed from the handle assembly 14. Specifically, the plunger 154 moves with respect to the housing 142 along the axis 170 to a retracted position (FIG. 7C) by the bias of the second spring 166 when the plunger 154 is in the extended position and in response to the pressure body 146 moving from the second position to the first position. In other words, when the plunger 154 is extended and the pod assembly 18 is removed, the plunger 154 automatically retracts without further user intervention. Advantageously, the handle assembly 14 is automatically reset and ready to receive another pod assembly 18 when one pod assembly is removed by a user. No additional user input (other than removing the pod assembly 18) is required to reset the handle assembly 14.

[0219] With reference to FIGS. 22 and 23, the handle assembly 314 includes a housing 892, a pressure body 896 movable with respect to the housing 892, a sleeve 900, the plunger 322, and the actuator 326. In the illustrated embodiment, the handle assembly 314 furtherTAXA-44420601includes at least one spring 904 that is positioned between the pressure body 896 and the plunger 322. The housing 892 defines an axis 908. In the illustrated embodiment, the housing 892 is cylindrical and the axis 908 is a center axis. In other embodiments, the housing 892 may be any suitable shape.

[0220] The pressure body 896 moves with respect to the housing 892 between a first position (FIG. 24C) and a second position (FIGS. 24A and 24B). In the illustrated embodiment, the pressure body 896 moves with respect to the housing 892 along the axis 908 between the first position when the pod assembly 318 is detached from the handle assembly 314 and the second position when the pod assembly 318 is attached to the handle assembly 314. The pressure body 896 includes an end wall 912 and a side wall 916. An opening 920 is formed in the end wall 912 and a bore 924 is formed by the side wall 916 and the end wall 912. As detailed herein, the plunger 322 extends through the opening 920 of the pressure body 896.|0221] With continued reference to FIGS. 22 and 23, the spring 904 biases the pressure body 896 to the first position. In the illustrated embodiment, the spring 904 biases the pressure body 896 away from the sleeve 900. In the illustrated embodiment, the spring 904 is positioned within the bore 924. A first end 928 of the spring 904 abuts the end wall 912 of the pressure body 896, and a second end 932 of the spring 904 abuts a flange 936 of the plunger 322. As such, when the pod assembly 318 is attached to the handle assembly 314, the pod assembly 318 moves the pressure body 896 to the second position, against the bias of the spring 904. When the pod assembly 318 is removed from the handle assembly 314, the spring 904 returns the pressure body 896 to the first position. In addition, the spring 904 biases the plunger 322 to a retracted position.

[0222] With continued reference to FIGS. 22 and 23, the handle assembly 314 further includes at least one aperture 940 formed in the sleeve 900, and at least one ball 944 positioned in the aperture 940. In the illustrated embodiment, the handle assembly 314 includes four apertures 940 and four balls 944, with one ball corresponding to each aperture. In other embodiments, any number of balls and apertures in the sleeve may be utilized. The balls 944 may be referred to as ball bearings or spheres.10223] In the illustrated embodiment, the sleeve 900 is stationary relative to the housing 892. The sleeve 900 includes a first cylindrical wall portion 948, a second cylindrical wall portion 952, and a ledge 956 extending between the first cylindrical wall portion 948 and theTAXA-44420601second cylindrical wall portion 952. The apertures 940 are formed in the first cylindrical wall portion 948. In the illustrated embodiment, the first cylindrical wall portion 948 has a smaller diameter than the second cylindrical wall portion 952. The handle assembly 314 further includes a retention ring 960 with a plurality of fingers 964 extending through corresponding notches 966 formed in the ledge 956. The retention ring 960 advantageously keeps the balls 944 in proper position. In the illustrated embodiment, the actuator 326 includes a plurality of snap fingers 968 that couple to the ledge 956 of the sleeve 900 upon assembly of the handle assembly 314.

[0224] With continued reference to FIGS. 22 and 23, the plunger 322 has an outer surface 972 with at least one helical groove 976. In the illustrated embodiment, a plurality of helical grooves 976 is formed in the outer surface 972 of the plunger 322 (e.g., one helical groove 976 for each of the balls 944 included in the handle assembly 314). Each helical groove 976 is configured to receive the corresponding ball 944 when the pressure body 896 is in the second position. In other words, the ball 944 is positioned outside the helical groove 976 when the pressure body 896 is in the first position, and the pressure body 896 retains the ball 944 within the helical groove 976 when the pressure body 896 is in the second position. In the illustrated embodiment, the side wall 916 of the pressure body 896 includes a contact surface 980 configured to abut the ball 944. In the illustrated embodiment, the contact surface 980 is beveled to cause radially inward motion of the ball 944 as the pressure body 896 moves along the axis 908 to the second position.|0225] With continued reference to FIGS. 22 and 23, the actuator 326 includes a stem 984 coupled to the plunger 322 for co-rotation with the plunger 322 about the axis 908. In the illustrated embodiment, the stem 984 is non-circular. In the illustrated embodiment, the actuator 326 includes a graspable portion 988 with knurling. In the illustrated embodiment, the handle assembly 314 further includes a bumper 992 positioned to abut the plunger 322 when the plunger 322 is in the retracted position. Advantageously, the bumper 992 dampens the impact of the plunger 322 returning to the retracted position. With reference to FIG. 25, the actuator 326 is only permitted to rotate about the axis 908 in one direction. A pawl 996 positioned on the actuator 326 interfaces with a plurality of teeth 1000 formed on an outer surface 1004 of the sleeve 900 to permit one w ay rotation and to advantageously prevent the plunger 322 from being back driven when the plunger 322 is extended. In other words, the plunger 322 advantageously holds its position when extended and while the pod assembly 318 remains attached.TAXA-44420601

[0226] With reference to FIG. 25, in some embodiments, the handle assembly 314 further includes a near field communication (NFC) tag 1008 positioned within the housing 892. In some embodiments, the NFC tag 1008 is positioned within a recess 1012 formed in an outer surface 1016 of the pressure body 896. In some embodiments, the NFC tag is associated with a particular pod assembly and directs a user to pod-specific information (e.g., batch number, expiration date, etc.) or user-specific information (e.g.. user-specific web pages, order history, etc.), or general user information (e.g., instructions, product information, etc.).

[0227] In operation, the plunger 322 moves with respect to the housing 892 along the axis 908 to an extended position (FIG. 24B) in response to rotation of the actuator 326 about the axis 908 when the pressure body 896 is in the second position. In other words, when the pressure body 896 is in the second position, the plunger 322 translates along the axis 908 relative to the stem 984 in response to the stem 984 and the plunger 322 co-rotating about the axis 908. Advantageously, the plunger 322 does not translate along the axis 908 in response to actuation of the actuator 326 when the pressure body 896 is in the first position. In other words, the plunger 322 will not extend in response to user actuation of the actuator 326 when there is no pod assembly 318 attached to the handle assembly 314.

[0228] As discussed in further detail herein, the plunger 322 of the handle assembly 314 automatically retracts from the extended position to the retracted position in response to the pod assembly 318 being removed from the handle assembly 314. Specifically, the plunger 322 moves with respect to the housing 892 along the axis 908 to a retracted position (FIG. 24C) by the bias of the spring 904 when the plunger 322 is in the extended position and in response to the pressure body 896 moving from the second position to the first position. In other words, when the plunger 322 is extended and the pod assembly 318 is removed, the plunger 322 automatically retracts without further user intervention. Advantageously, the handle assembly 314 is automatically reset and ready to receive another pod assembly 318 when one pod assembly is removed by a user. No additional user input (other than removing the pod assembly 318) is required to reset the handle assembly 314. In the illustrated embodiment, the sleeve 900 and the plunger 322 abut with a self-aligning interface 1020. In the illustrated embodiment, the self-aligning interface 1020 includes a pl ural i ty of mating ridges 1024 formed on the sleeve 900 and the plunger 322. Advantageously, the self-aligning interface 1020 ensures proper alignment of the plunger 322 with respect to the sleeve 900 upon the plunger 322 returning to the retracted position.5. System Operation and MethodsTAXA-44420601[0229J With reference to FIG. 2, the pod assembly 18 is removably coupled to the handle assembly 14. In the illustrated embodiment, the pod assembly 18 and the handle assembly 14 form a bayonet style interface 266 with the connector 130 on the pod assembly 18 and a corresponding groove 270 on the handle assembly 14. In other words, the pod assembly 18 is attached to the handle assembly 14 with insertion along the axis 170 and rotation about the axis 170. When assembled together, the pod axis 25 is co-axial with the axis 170 of the handle assembly 14.

[0230] With reference to FIGS. 7A-7C, operation of the system 10 is illustrated. As detailed herein, the handle assembly 14 includes the plunger 154 which is moveable in response to user actuation of the actuator 158.

[0231] FIG. 7A illustrates the system 10 with the pod assembly 18 attached to the handle assembly 14 and the plunger 154 in a retracted position, which is representative of when the pod assembly 18 is first coupled to the handle assembly 14 by the user. The ball 206 is retained within the helical groove 242 by the pressure body 146 being in the second position, such that rotation of the actuator 158 will cause rotation and translation of the plunger 154.

[0232] FIG. 7B illustrates the system 10 with the pod assembly 18 attached to the handle assembly 14 and the plunger 154 in an extended position, which is representative of when the composition 38 and the fluid 42 are dispensed in response to user actuation of the actuator 158. In the illustrated embodiment, user actuation of the actuator 158 includes rotation of the actuator 158 about the axis 170. In the illustrated embodiment, the plunger 154 translates along the axis 170 in response to user actuation of the actuator 158. The plunger 154 extends into the pod assembly 18 in response to user actuation of the actuator 158, causing the first cartridge 30 and the second cartridge 34 to open. In the illustrated embodiment, the plunger 154 abuts the second cartridge 34. Moving the pod assembly 18 from the first configuration (FIG. 7A) to the second configuration (FIG. 7B) requires an external force acting upon the pod assembly 18 (e.g., the plunger 154 acting on the pod assembly 18).

[0233] The composition 38 and the fluid 42 are dispensed from the outlet 26 in response to user actuation of the actuator 158. As detailed herein, the composition 38 may be a skin probiotic that is genetically engineered and formulated as a desiccated skin probiotic powder. As the plunger 154 extends, the second cartridge 34 is opened by contact with the plurality of second piercing elements 62 of the puncture member 46. As the plunger 154 continues to extend, the puncture member 46 also comes into contact with the first cartridge 30, and theTAXA-44420601second seal 82 of the first cartridge 30 is broken by the plurality of first piercing elements 58. At the same time, the piercing end 122 of the stem 118 comes into contact with the first cartridge 30, thereby breaking the first seal 78 of the first cartridge 30. In summary, the first seal 78 and the second seal 82 of the first cartridge 30 and the first seal 106 of the second cartridge 34 are broken in response to user actuation of the actuator 158.|0234] Once the first cartridge 30 and the second cartridge 34 are open, the fluid 42 pushes and carries the powder skin probiotic composition 38 through the outlet 26 and rehydrates the composition 38 in response to user actuation of the actuator 158. The fluid 42 moves through the first cartridge 30. Advantageously, the fluid 42 is suitable for transporting a desiccated probiotic powder composition 38 from the first cartridge 30 to the outlet 26. In other words, moving from the first configuration (FIG. 7A) to the second configuration (FIG.7B) causes the fluid 42 to move toward the composition 38 to at least partially combine with the composition 38.|0235] FIG. 7C illustrates the system 10 with the pod assembly 18 removed from the handle assembly 14 and the plunger 154 automatically retracting to the retracted position. The plunger 154 retracts in response to the pod assembly 18 being removed from the handle assembly 14. When the user is done applying the contents of the pod assembly 18, the pod assembly 18 can be removed and discarded, thereby causing the handle assembly 14 to automatically reset and be ready to receive another pod assembly.

[0236] With reference to FIG. 17, the pod assembly 318 is removably coupled to the handle assembly 314. In the illustrated embodiment, the pod assembly 318 and the handle assembly 314 form a bayonet style interface 1030 with the connector 454 on the pod assembly 318 and a corresponding groove 1034 on the handle assembly 314. In other words, the pod assembly 318 is attached to the handle assembly 314 with insertion along the axis 908 and rotation about the axis 908. When assembled together, the pod axis 414 is co-axial with the axis 908 of the handle assembly 314.

[0237] With reference to FIGS. 24A-24C, operation of the system 310 is illustrated. As detailed herein, the handle assembly 314 includes the plunger 322 which is moveable in response to user actuation of the actuator 326.|0238] FIG. 24A illustrates the system 310 with the pod assembly 318 attached to the handle assembly 314 and the plunger 322 in a retracted position, which is representative of when the pod assembly 318 is first coupled to the handle assembly 314 by the user. The ballTAXA-44420601944 is retained within the helical groove 976 by the pressure body 896 being in the second position, such that rotation of the actuator 326 will cause rotation and translation of the plunger 322.

[0239] FIG. 24B illustrates the system 310 with the pod assembly 318 attached to the handle assembly 314 and the plunger 322 in an extended position, which is representative of when the composition 338 and the fluid 342 are dispensed in response to user actuation of the actuator 326. In the illustrated embodiment, user actuation of the actuator 326 includes rotation of the actuator 326 about the axis 908. In the illustrated embodiment, the plunger 322 translates along the axis 908 in response to user actuation of the actuator 326. The plunger 322 extends into the pod assembly 318 in response to user actuation of the actuator 326, causing the fluid cartridge 346 to move tow ards the puncture member 350 and to open. In the illustrated embodiment, the plunger 322 abuts a recess 402 formed on the fluid cartridge 346. Moving the pod assembly 318 from the first configuration (FIG. 24 A) to the second configuration (FIG. 24B) requires an external force acting upon the pod assembly 318 (e.g., the plunger 322 acting on the pod assembly 318).

[0240] The composition 338 and the fluid 342 are dispensed from the outlet 334 in response to user actuation of the actuator 326. As detailed herein, the composition 338 may be a skin probiotic that is genetically engineered and formulated as a tablet. As the plunger 322 extends, the fluid cartridge 346 is opened by contact with the plurality of piercing elements 366 of the puncture member 350. In other words, the seal 394 of the fluid cartridge 346 is broken in response to user actuation of the actuator 326.|0241] Once the fluid cartridge 346 is open, the fluid 342 is pushed through the channels 386 of the puncture member 350 as the plunger 322 continues to extend. In the illustrated embodiment, the fluid 342 moves through the puncture member 350 before exiting the outlet 334. The moving fluid 342 comes into contact with the composition 338 tablet positioned within the puncture member 350. As the fluid 342 moves past the composition 338 tablet, portions of the composition 338 are carried away with the moving fluid 342. At least a portion of the composition 338 tablet and the fluid 342 at least partially mix before dispensing at the outlet 334. In other words, moving from the first configuration (FIG. 24A) to the second configuration (FIG. 24B) causes the fluid 342 to move toward the composition 338 to at least partially combine with the composition 338. In some embodiments, the composition 338 is re-hydrated by the fluid 342 in response to user actuation of the actuatorTAXA-44420601326. Advantageously, the fluid 342 is suitable for transporting a portion of the composition 338 tablet to the outlet 334.

[0242] FIG. 24C illustrates the system 310 with the pod assembly 318 removed from the handle assembly 314 and the plunger 322 automatically retracting to the retracted position. The plunger 322 retracts in response to the pod assembly 318 being removed from the handle assembly 314. When the user is done applying the contents of the pod assembly 318, the pod assembly 318 can be removed and discarded, thereby causing the handle assembly 314 to automatically reset and be ready to receive another pod assembly.

[0243] The systems disclosed herein may utilized in a variety of uses including, but not limited to: cosmetic; pharmaceutical; topical application; direct skin contact; direct underarm application; for achieving a cosmetic or pharmaceutical benefit; deodorant; eczema relief; mosquito repellent; or a sunscreen.6. Examples

[0244] It will be readily apparent to those skilled in the art that other suitable modifications and adaptations of the methods of the present disclosure described herein are readily applicable and appreciable, and may be made using suitable equivalents without departing from the scope of the present disclosure or the aspects and embodiments disclosed herein. Having now described the present disclosure in detail, the same will be more clearly understood by reference to the fol low ing examples, which are merely intended only to illustrate some aspects and embodiments of the disclosure, and should not be view ed as limiting to the scope of the disclosure. The disclosures of all journal references, U.S. patents, and publications referred to herein are hereby incorporated by reference in their entireties.

[0245] The present disclosure has multiple aspects, illustrated by the following non-limiting examples.Example 1

[0246] With reference to FIG. 26, total viable skin probiotic CFUs delivered from an extrusion device is illustrated using tablets formulated with increasing mass fractions of lyophilized probiotic powder (0.1%, 1%, 10%, 90% w / w).

[0247] With reference to FIG. 27, the lyophilized skin probiotic cells remain viable for at least 7 months.

[0248] Lyophilizing strains. Briefly, 50mL of the strain was grown overnight in TSB at 37°C. The overnight culture w as centrifuged (4,000 g, 10 min) and resuspended (lOx dilution)TAXA-44420601in PBS with 10% (m / v) trehalose and 10% (m / v) inulin, and ImL of this suspension was poured into 1 ,5mL microfuge tubes. The mixture was thoroughly vortexed and stored at -80 °C before freeze-drying or spray drying.

[0249] Samples were lyophilized in open microfuge tubes using a VirTis Advantage Pro per the manufacturer’s protocol. During lyophilization, samples were first kept at -40 °C with a condenser temperature of -55 °C and chamber pressure of 10 Pa for 18 hours, and then the condenser was turned off, and the samples remained at room temperature and 10 Pa for 5 hours. After lyophilization, samples were kept in sealed 1.5mL microfuge tubes at room temperature and kept under pressure.

[0250] Tablet preparation. Lyophilized probiotic powders were incorporated into a tablet matrix and compressed into oval tablets (target hardness = 2). Tablets were prepared at varying lyophilized powder mass fractions (0.1%, 1%, 10%, 90% w / w). The non-probiotic fraction consisted of 0.5% SSF and sorbitol for the remaining balance. For extrusion testing, tablets were formulated for use with a 2% (w / w) aqueous hyaluronic acid vehicle containing 0.3% DHA (dehydroacetic acid) as a preservative.

[0251] CFU enumeration. For all CFU enumeration experiments, a pre-weighed 50 mL conical tube was used to collect the sample. The mass of the conical and sample was recorded. A defined volume of citrate-buffered saline (CBS; lx, pH 5.4) was then added (10 mL), and the conical was reweighed. The total mass of the resulting suspension (sample + CBS) was calculated from the mass difference and used for back-calculation of total CFUs and CFUs-per-gram.

[0252] For samples extruded from devices. Devices were actuated to extrude material for ~1 s into the conical. Extrudate was resuspended in CBS (lx, pH 5.4) by mixing thoroughly. Serial 10-fold dilutions were prepared promptly, and appropriate dilutions (10A-5, 10A-6, and 10A-7) were plated on tryptic soy agar (TSA). Plates were incubated under standard growth conditions for the strain until colonies were countable, and CFU were enumerated from plates within the countable range. A negative-control plate (no sample) was included to confirm absence of contamination.

[0253] For long-term stability. Identical replicates containing lyophilized cells were prepared and stored. From immediately after preparation until at least 209 days after lyophilization, the CFU / g of a samples was performed as follows: a sample was resuspended into atared 50mL tube containing lOmL CBS (1 x, pH 5.4) and resuspended mixing thoroughly. Serial 10-fold dilutions were prepared promptly, and appropriate dilutions (10A-5, 10A-6, and 10A-7) were plated on tryptic soy agar (TSA). Plates were incubated under standard growthTAXA-44420601conditions for the strain until colonies were countable, and CFU were enumerated from plates within the countable range. A negative-control plate (no sample) was included to confirm absence of contamination.

[0254] It is understood that the foregoing detailed description and accompanying examples are merely illustrative and are not to be taken as limitations upon the scope of the disclosure, which is defined solely by the appended claims and their equivalents.

Claims

TAXA-44420.601CLAIMSWhat is claimed is:

1. An assembly comprising:a housing with an outlet;a composition; anda fluid;wherein the assembly is movable between a first configuration and a second configuration; andwherein the composition and the fluid are separated in the first configuration; and wherein the composition and the fluid are at least partially combined and dispensed through the outlet in the second configuration.

2. The assembly of claim 1, wherein the composition is at least one skin probiotic.

3. The assembly of claim 2. wherein the at least one skin probiotic is genetically engineered.

4. The assembly of claim 2 or claim 3, wherein the at least one skin probiotic comprises a Staphylococcus strain, a Cutibacterium strain, a Corynebacterium strain, a Bacillus strain, a Micrococcus strain and / or a Lactobacillus strain.

5. The assembly of any one of claims 2 to 4, wherein the at least one skin probiotic comprises a Coagulase-negative Staphylococci (CoNS).

6. The assembly of any one of claims 2 to 5, wherein the at least one skin probiotic comprises one or more of S. hominis, S. lugdunensis, S. haemolyticus, S. epidermidis, and / or S. cohnii.

7. The assembly of any one of claims 2 to 6, wherein the at least one skin probiotic is genetically engineered to comprise a disruption in at least one endogenous gene.

8. The assembly of claim 2. wherein the at least one skin probiotic comprises a Staphylococcus hominis strain having a disrupted patB gene.TAXA-44420.6019. The assembly of claim 2. wherein the at least one skin probiotic comprises a Staphylococcus hominis strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof.

10. The assembly of claim 2. wherein the at least one skin probiotic comprises a Staphylococcus lugdunensis strain having a disrupted patB gene.

11. The assembly of claim 2, wherein the at least one skin probiotic comprises a Staphylococcus lugdunensis strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof.

12. The assembly of claim 2, wherein the at least one skin probiotic comprises a Staphylococcus haemolyticus strain having a disrupted patB gene.

13. The assembly of claim 2. wherein the at least one skin probiotic comprises a Staphylococcus haemolyticus strain having a disrupted patB gene, a disrupted pepV gene, a disrupted dtpT gene, or any combination thereof.

14. The assembly of any one of claims 2 to 13, wherein the at least one skin probiotic is formulated as a desiccated skin probiotic powder.

15. The assembly of any one of claims 2 to 13, wherein the at least one skin probiotic is formed as a tablet.

16. The assembly of any one of claims 2 to 15, wherein, in the second configuration, the fluid pushes at least a portion of the at least one skin probiotic through the outlet and rehydrates the at least one skin probiotic.

17. The assembly of claim 16, wherein viable colony-forming units (CFUs) are delivered by dispensing the fluid through the outlet.

18. The assembly of claim 15, wherein the tablet comprises 0.1% to 90% (w / w) lyophilized skin probiotic powder.TAXA-44420.60119. The assembly of any one of claims 14.

15. 17, or 18, wherein the desiccated skin probiotic powder or tablet retains at least 10% of an initial viable CFU count after storage for at least 1 day.

20. The assembly of claim 19, wherein the storage is for at least 7 days.

21. The assembly of claim 19, wherein the storage is for at least 1 month.

22. The assembly of claim 19, wherein the storage is for at least 6 months.

23. The assembly of any one of claims 1 to 22, wherein the fluid is a water-based fluid.

24. The assembly of claim 23, wherein the water-based fluid is an aqueous solution, an aqueous gel, an aqueous cream, or a combination thereof.

25. The assembly of claim 23, wherein the water-based fluid includes silk peptides, xanthan gum, diutan gum, hyaluronic acid, or any combination thereof.

26. The assembly of any one of claims 1 to 25, wherein the fluid is preservative free.

27. The assembly of any one of claims 1 to 25, wherein the fluid is gamma or electron beam irradiated.

28. The assembly of any of claims 1-27, wherein moving from the first configuration to the second configuration requires an external force acting upon the assembly.

29. The assembly of any of claims 1-28, wherein moving from the first configuration to the second configuration causes the fluid to move toward the composition to at least partially combine with the composition.

30. The assembly of any of claims 1-28, wherein moving from the first configuration to the second configuration causes the composition to move toward the fluid to at least partially combine with the fluid.TAXA-44420.60131. The assembly of any of claims 1-28. wherein moving from the first configuration to the second configuration causes the composition and the fluid to move toward a mixing zone where the composition and the fluid are at least partially combined.

32. The assembly of any of claims 1-28, wherein the composition is positioned between the fluid and the outlet in the first configuration.

33. The assembly of any of claims 1-28, wherein the fluid is positioned between the composition and the outlet in the first configuration.

34. The assembly of any of claims 1-28, wherein the composition is positioned a first distance from the outlet in the first configuration, and wherein the fluid is positioned a second distance from the outlet in the first configuration; and wherein the first distance is equal to the second distance.

35. The assembly of any of claims 1-28, wherein the composition is at least partially surrounded by the fluid in the first configuration.

36. The assembly of any of claims 1-28. wherein the fluid is at least partially surrounded by the composition in the first configuration.

37. The assembly of any of claims 1-28, wherein the composition is positioned within the housing in the first configuration, wherein the fluid is positioned within the housing in the first configuration.

38. The assembly of any of claims 1-28, further comprising a cartridge, and wherein the fluid is positioned within the cartridge.

39. The assembly of claim 38, wherein the cartridge includes a cartridge housing and a seal coupled to the cartridge housing.TAXA-44420.60140. The assembly of claim 39, wherein the cartridge housing includes an aperture and wherein the seal covers the aperture in the first configuration; and wherein the seal is broken in the second configuration.

41. The assembly of any of claims 1-40, further comprising a puncture member positioned within the housing.

42. The assembly of any of claims 1 -40, wherein the outlet is at a first end of the housing and the housing includes a connector at a second end of the housing opposite the first end.

43. The assembly of claim 42, wherein the second end of the housing includes an opening configured to receive a plunger.

44. The assembly of any of claims 1-43, wherein the outlet is partially formed by a stem with a plurality of apertures.

45. The assembly of any of claims 1-44, wherein the housing includes an upper body and a lower body; wherein the outlet is formed in the upper body.

46. The assembly of claim 45, wherein the lower body includes a window to receive a pip formed on the upper body.

47. The assembly of claim 45, further comprising a cartridge, wherein the fluid is positioned within the cartridge, and wherein the lower body includes an opening such that the cartridge is mechanically accessible through the opening.

48. The assembly of claim 47, wherein the cartridge includes a housing with a recess formed in a bottom surface.

49. The assembly of any of claims 1-48, further comprising a puncture member positioned within the housing, and wherein the composition is at least partially positioned within the puncture member in the first configuration.TAXA-44420.60150. The assembly of claim 49, wherein the composition is formed as a tablet, and wherein the puncture member includes a cavity and at least one retaining rib extending into the cavity and configured to secure the tablet within the cavity.

51. The assembly of claim 50, wherein the outlet is partially formed by a stem in the housing, and wherein the puncture member is at least partially positioned within the stem.

52. The assembly of claim 49, wherein the puncture member includes at least one piercing element formed at an end.

53. The assembly of any of claims 1-52. further comprising a first sealing member positioned between a cartridge for the fluid and the housing; and further comprising a second sealing member positioned betw een a puncture member and the housing.

54. The assembly of any of claims 1-44, wherein the composition is positioned within a first cartridge and the fluid is positioned within a second cartridge.

55. The assembly of claim 54, wherein the first cartridge includes a first cartridge housing, a first seal coupled to the first cartridge housing, and a second seal coupled to the first cartridge housing.

56. The assembly of claim 55, wherein the first seal and the second seal are broken in the second configuration.

57. The assembly of claim 55, wherein the first cartridge housing includes a first aperture at a first end and a second aperture at a second end, opposite the first end; and wherein the first seal covers the first aperture in the first configuration and the second seal covers the second aperture in the first configuration.

58. The assembly of any one of claims 54-57, wherein the first cartridge is positioned between the outlet and the second cartridge.TAXA-44420.60159. The assembly of any of claims 54-58, wherein the first cartridge and the second cartridge are positioned within a channel of the housing and are movable with respect to the housing.

60. The assembly of claim 59, wherein the first cartridge and the second cartridge abut the channel.

61. The assembly of any of claims 54-60, further comprising a puncture member positioned between the first cartridge and the second cartridge.

62. The assembly of claim 61, wherein the puncture member includes a first piercing element positioned on a first side configured to open the first cartridge and a second piercing element positioned on a second side, opposite the first side, configured to open the second cartridge.

63. The assembly of claim 61, wherein the puncture member includes at least one opening configured to receive the fluid in the second configuration.

64. The assembly of claim 61, wherein, in the second configuration, the second cartridge moves with respect to the housing to cause the puncture member to abut the second cartridge and the first cartridge to thereby open the second cartridge and the first cartridge.

65. A system comprising:a handle assembly with a plunger movable in response to user actuation of an actuator; anda pod assembly coupled to the handle assembly; wherein the pod assembly includes an outlet, a composition, and a fluid;wherein the composition and the fluid are dispensed from the outlet in response to user actuation of the actuator.

66. The system of claim 65, wherein the handle assembly defines a center axis; and wherein the plunger translates along the center axis in response to user actuation of the actuator.TAXA-44420.60167. The system of claim 66, wherein user actuation of the actuator includes rotation of the actuator about the center axis.

68. The system of any one of claims 65 to 67, wherein the pod assembly is removably coupled to the handle assembly.

69. The system of claim 68, wherein the pod assembly and the handle assembly form a bayonet sty le interface.

70. The system of any one of claims 65 to 69, wherein the composition is at least one skin probiotic; wherein the at least one skin probiotic is genetically engineered and is formulated as a desiccated skin probiotic powder or as a tablet.

71. The system of any one of claims 65 to 70, wherein the fluid is preservative free and is sterilized.

72. The system of any one of claims 65 to 71, wherein the composition is positioned within a cartridge that includes a cartridge housing, a first seal coupled to the cartridge housing, and a second seal coupled to the cartridge housing, and wherein the first seal and the second seal are broken in response to user actuation of the actuator.

73. The system of any one of claims 65 to 71, wherein the fluid is positioned within a cartridge that includes a cartridge housing and a seal coupled to the cartridge housing; and wherein the seal is broken in response to user actuation of the actuator; and wherein the fluid is a water-based fluid, and wherein the water-based fluid includes silk peptides, xanthan gum, diutan gum, hyaluronic acid, or any combination thereof.

74. The system of any one of claims 65 to 73, wherein the composition is at least one skin probiotic; and wherein the fluid pushes the at least one skin probiotic through the outlet and re-hydrates the at least one skin probiotic in response to user actuation of the actuator.

75. The system of any one of claims 65 to 73, wherein user actuation dispenses colonyforming units (CFUs) of viable skin probiotics from the outlet.TAXA-44420.60176. The system of claim 75, wherein the desiccated skin probiotic powder or tablet retains at least 10% of an initial viable CFU count after storage for at least 1 day.

77. The system of claim 76, wherein the storage is for at least 7 days.

78. The system of claim 76, wherein the storage is for at least 1 month.

79. The system of claim 76, wherein the storage is for at least 6 months.

80. The system of any one of claims 65 to 74, wherein the plunger extends into the pod assembly in response to user actuation of the actuator.

81. The system of claim 80, wherein the plunger retracts in response to the pod assembly being removed from the handle assembly.

82. A handle assembly comprising:a housing defining an axis;a pressure body movable with respect to the housing between a first position and a second position;a sleeve including an aperture;a plunger having an outer surface with a helical groove;at least one spring that biases the pressure body to the first position;an actuator including a stem coupled to the plunger for co-rotation with the plunger about the axis; anda ball positioned in the aperture formed in the sleeve;wherein the ball is positioned outside the helical groove when the pressure body is in the first position; and wherein the pressure body retains the ball within the helical groove when the pressure body is in the second position; andwherein the plunger moves with respect to the housing along the axis to an extended position in response to rotation of the actuator about the axis when the pressure body is in the second position; andwherein the plunger moves with respect to the housing along the axis to a retracted position by the bias of the at least one spring when the plunger is in the extended position and in response to the pressure body moving from the second position to the first position.TAXA-44420.60183. The handle assembly of claim 82, wherein the at least one spring is a spring positioned between the pressure body and the plunger.

84. The handle assembly of claim 82, wherein the at least one spring includes a first spring positioned between the pressure body and the sleeve, and wherein the at least one spring includes a second spring positioned between the plunger and the sleeve; wherein the first spring biases the pressure body to the first position; and wherein the plunger moves with respect to the housing along the axis to a retracted position by the bias of the second spring.

85. The handle assembly of any one of claims 82-84, wherein the pressure body moves with respect to the housing along the axis between the first position and the second position.

86. The handle assembly of any one of claims 82-85, wherein the pressure body includes an end wall and a side wall; wherein an opening is formed in the end wall, and wherein a bore is formed by the side wall and the end wall.

87. The handle assembly of claim 86, wherein the side wall includes a contact surface configured to abut the ball.

88. The handle assembly of claim 86, wherein the plunger extends through the opening.

89. The handle assembly of claim 86, wherein the at least one spring is positioned within the bore, and wherein a first end of the at least one spring abuts the end wall of the pressure body and a second end of the at least one spring abuts a flange of the plunger.

90. The handle assembly of any one of claims 82-89, wherein the at least one spring biases the pressure body away from the sleeve.

91. The handle assembly of any one of claims 82-90, wherein the sleeve is stationary relative to the housing.

92. The handle assembly of any one of claims 82-91, wherein the sleeve includes a first cylindrical wall portion, a second cylindrical wall portion, and a ledge extending between theTAXA-44420.601first cylindrical wall portion and the second cylindrical wall portion; wherein the aperture is formed in the first cylindrical wall portion.

93. The handle assembly of claim 92, further comprising a retention ring with a finger extending through a notch formed in the ledge.

94. The handle assembly of claim 93, wherein the actuator includes a snap finger coupled to the ledge of the sleeve.

95. The handle assembly of any one of claims 82-94, wherein the plunger does not translate along the axis in response to actuation of the actuator when the pressure body is in the first position.

96. The handle assembly of any one of claims 82-95, wherein, when the pressure body is in the second position, the plunger translates along the axis relative to the stem in response to the stem and the plunger co-rotating about the axis.

97. The handle assembly of claim 96, wherein the stem is non-circular.

98. The handle assembly of any one of claims 82-97, wherein the actuator only rotates about the axis in one direction.

99. The handle assembly of claim 98, further comprising a pawl positioned on the actuator and a plurality of teeth formed on the sleeve.

100. The handle assembly of any one of claims 82-99, wherein the housing is cylindrical and the axis is a center axis.

101. The handle assembly of any one of claims 82-100, further comprising a bumper positioned to abut the plunger when the plunger is in the retracted position.

102. The handle assembly of any one of claims 82-101, further comprising a near field communication tag positioned within the housing.TAXA-44420.601103. The handle assembly of any one of claims 82-102, wherein the sleeve and the plunger abut with a self-aligning interface.

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