WO2021219891A1

WO2021219891A1 - Ingestible and modular capsule for sample collection, monitoring, and/or data detection

Info

Publication number: WO2021219891A1
Application number: PCT/EP2021/061486
Authority: WO
Inventors: Phoebe HESELTINE; Mariam ELGABRY
Original assignee: Enteromics Ltd.
Priority date: 2020-05-01
Filing date: 2021-04-30
Publication date: 2021-11-04

Abstract

The present disclosure provides for a modular ingestible capsule that may be biodegradable. In one example, the ingestible capsule includes a selectively expandable material and a genetic circuit positioned within the selectively expandable material. The selective expansion of the selectively expandable material exposes the genetic circuit to bodily molecules or fluids at a predicable location within the gastrointestinal tract. The genetic circuit can then detect characteristics and relay those characteristics to a device or be retrieved and analyzed.

Description

INGESTIBLE AND MODULAR CAPSULE FOR SAMPLE COLLECTION, MONITORING,

AND/OR DATA DETECTION

BACKGROUND

[0001] Collecting samples and tracking data within the human body can be difficult and result in inaccurate or contaminated samples and/or incomplete data sets. Further, many testing and sampling procedures are invasive and not user friendly as they require expensive sequencing methods, transport of biological samples and difficult sample collection.

SUMMARY

[0002] In one embodiment, an ingestible capsule is disclosed. The capsule may include a vessel with an expandable material positioned within the vessel and a sealing assembly movable from an open position to a sealed position upon expansion of the expandable material. The capsule may also include a coating positioned over a portion of the vessel and configured to selectively dissolve to expose one or more inlets into the vessel.

[0003] The coating may be positioned over only portions of the vessel, such as over one or more of the inlets.

[0004] The capsule may include a sealing assembly that has a plunger and a cap coupled to the plunger. As the expandable material expands, the plunger moves to seal around an open end of the vessel.

[0005] The vessel may define a sample compartment configured to receive fluid from outside of the vessel, where in the sealed position, the sealing assembly prevents fluid from entering or exiting the sample compartment.

[0006] The sealing assembly may include a sample container configured to move longitudinally within the vessel.

[0007] In another embodiment, a capsule is disclosed that includes a coating, a body defining a cavity therein, a port in fluid communication with the cavity, and an expandable material positioned within the cavity. In a first state, the expandable material is positioned to allow fluid communication between the port and the cavity and in a second state the expandable material is positioned to prevent fluid communication between the port and the cavity.

[0008] The capsule may include a genetic circuit and/or electronic components that allow in vivo monitoring and data collection. This type of in vivo monitoring and data collection is not possible with conventional devices.

[0009] In yet another embodiment, a capsule is disclosed having a hydrophilic polymer and a circuitry component positioned within the hydrophilic polymer. [0010] The hydrophilic polymer may be an amorphous shape, such as one that is user friendly (e.g., easily consumed and/or aesthetically pleasing). The circuitry component may include one or more sensors, electronic components (e.g., data transmission elements), and/or genetic circuits. The hydrophilic polymer may be used to selectively expose the circuitry component to areas within a body and/or activate the circuitry components.

[0011] The hydrophilic polymer may activate the circuit component.

[0012] The hydrophilic polymer may increase a sensitivity of the circuity component. [0013] An ingestible capsule is disclosed that includes a selectively expandable material and a genetic circuit positioned within the selectively expandable material. The selective expansion of the selectively expandable material exposes the genetic circuit to bodily molecules (e.g., biomarkers) or fluids at a predicable location within the gastrointestinal tract.

[0014] The capsule may include an expandable material that is a hydrogel.

[0015] The capsule may include a genetic circuit that is a cell free system.

[0016] The capsule may include the expandable material that is configured to crowd selected bodily molecules (e.g., biomarkers) to enhance detectability of the selected bodily molecules by the genetic circuit.

[0017] The capsule may include an expandable material, such as hydrogel, that preserves the bodily molecules or fluids.

[0018] In various embodiments, the capsules may be modular and configured to include elements that allow collection of a fluid or biological sample and/or detect characteristics. In many instances, the capsules may optionally include a cassette or housing that includes a circuitry component, where the specific implementation of the circuitry component is variable based on the desired elements or characteristics to be detected.

[0019] In various embodiments, a capsule includes a hydrogel and a cell free system that allows in situ monitoring via an ingestible device. The hydrogel may enhance the sensing and/or preserve the biomolecules within the device. For example, the capsule may be configured to allow in situ monitoring of microRNAs. In some examples, the cell free system may be embedded in the hydrogel.

[0020] In some examples, a capsule including a hydrogel and a genetic circuit positioned within hydrogel is formed as an ingestible device.

[0021] An ingestible capsule is disclosed that may include a coating, a body defining a cavity therein and comprising a port in fluid communication with the cavity. The capsule may also include an expandable material positioned within the cavity, where in a first state the expandable material is positioned to allow fluid communication between the port and the cavity and in a second state the expandable material is positioned to prevent fluid communication between the port and the cavity.

[0022] The expandable material may be a hydrogel, and in the first state the hydrogel is unexpanded or in an original configuration and in a second state is expanded.

[0023] The capsule may include a circuitry component positioned within the body configured to detect one or more characteristics of fluid received within the cavity.

[0024] In various examples, the capsule may be modular, with features between different embodiments swappable between embodiments. This may allow the capsule to be tailored to particular users and/or to a desired sample or characteristic to be detected.

[0025] A method for assembling a capsule is disclosed. The method may include assembling a genetic circuit, assembling a hydrogel and cross-linking the hydrogel, combining the genetic circuit and the hydrogel gel together, up-taking the cell free, such as on ice, freeze drying the combination, and combining with the capsule components, e.g., inserting into a capsule.

[0026] Additional embodiments and features are set forth in part in the description that follows and will become apparent to those skilled in the art upon examination of the specification or may be learned by the practice of the disclosed subject matter. A further understanding of the nature and advantages of the present disclosure may be realized by reference to the remaining portions of the specification and the drawings, which forms a part of this disclosure. One of skill in the art will understand that each of the various aspects and features of the disclosure may advantageously be used separately in some instances, or in combination with other aspects and features of the disclosure in other instances.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The description will be more fully understood with reference to the following figures in which components are not drawn to scale, which are presented as various examples of the present disclosure and should not be construed as a complete recitation of the scope of the disclosure.

[0028] Fig. 1 is an isometric view of a capsule.

[0029] Fig. 2 is a cross-section of the capsule taken along line 2-2 in Fig. 1.

[0030] Fig. 3A is a front elevation view of the capsule of Fig. 1 with a coating hidden. [0031] Fig. 3B is another cross-section view of the capsule similar to Fig. 2 with the coating hidden for clarity.

[0032] Fig. 4 is an exploded view of the capsule of Fig. 3A.

[0033] Figs. 5A-5E illustrate the capsule at different locations or points of time within a body of a user. [0034] Fig. 6 is a front elevation view of another example of a capsule.

[0035] Fig. 7 is an exploded view of the capsule of Fig. 6.

[0036] Fig. 8 is a cross-section view of the capsule taken along line 8-8 in Fig. 6.

[0037] Figs. 9A-9D illustrate the capsule at different locations or points of time within a body of a user.

[0038] Fig. 10 is a front elevation view of another example of a capsule.

[0039] Fig. 11 is an exploded view of the capsule of Fig. 10.

[0040] Fig. 12 is a cross-section of the capsule taken along line 12-12 in Fig. 10.

[0041] Figs. 13A-13E illustrate the capsule at different locations or points of time within a body of a user.

[0042] Fig. 14 is a top plan view of another example of a capsule.

[0043] Fig. 15 is front elevation view of another example of a capsule.

[0044] Fig. 16 is an exploded view of the capsule of Fig. 15.

[0045] Figs. 17A-17J illustrate the capsule of Fig. 15 at various stages during assembly and use.

[0046] Fig. 18 is a flow chart of an illustrative method for creating a capsule and sensor.

DETAILED DESCRIPTION

[0047] According to the present disclosure, in various examples, an ingestible capsule for collecting a sample and/or detecting characteristics of fluid(s), such as biological fluids, is disclosed. The ingestible capsule may include components that allow the capsule to selectively open or activate at predetermined locations within a body, such as within a location of the digestive tract of a human body. The capsule may include modular components, such as sealing components, sensing components, sampling assemblies, and the like, that can be substituted in and out for one another based on a particular user’s (e.g., patient) needs, e.g., the capsule may include a cassette or another support module that receives one or more sensors that can be activated or exposed to biological fluid at predetermined points in time or at locations within the human body. For example, the sensors can be exposed to microRNAs within the human body at selected locations based on the structure of the capsule.

[0048] As a specific example, the ingestible capsule may be configured to capture fluid from the small intestine, stomach, large intestine, colon, or the like, while also sealing the fluid compartment before and/or after collection to ensure that the sample is not contaminated from fluids and debris in other locations within and outside of the body (e.g., ensures that the contents of the capsule are not exposed to human fluids and/or body components). In other examples, the capsule may be differently configured and may not be “sealed” after fluid capture, depending on the desired configuration.

[0049] In one embodiment, the capsule may include a fluid compartment selectively sealed and unsealed by a plunger assembly or sealing assembly. The capsule may include a selectively dissolvable coating that when exposed to a particular pH level, after a predetermined amount of time, exposure to particular chemical or chemical combination, exposure to enzymes, microorganisms, pathogens, or the like, dissolves to open ports, remove an obstruction to the sealing assembly to allow it to open, or otherwise allow fluid into the capsule. Additionally, the plunger assembly is activated by an expandable material that expands in response to exposure to liquids, the exposure of which may be controlled by the dissolvable coating and/or characteristics of the expandable material. This selectively allows the plunger assembly to not be activated until the capsule is located at a desired position within the body. After activation, the plunger assembly defines a flow path into a sample compartment and due to pressure differentials, fluids within the body flow into the sample compartment. The plunger assembly may then close, such as response to the fluid compartment collecting a sufficient volume of sample, based on exposure to other pH levels, swell rate and/or expansion of the expandable material, and/or time limitation. The closure seals the sample compartment, ensuring a “clean” sample (e.g., without contamination) can be retrieved even after the capsule completes a journey to exit the body. [0050] In another embodiment, the capsule may omit the plunger assembly and include an expandable material that expands within the cavity to close off ports and prevent any further liquid or debris from exiting and/or entering the sample compartment. In some embodiments, the expandable material may act to capture the fluid itself and act as the storage compartment, e.g., the sample is stored within the expandable material causing it to expand.

[0051] In various embodiments, the capsule may include one or more circuitry components, such as sensing and data transmission components, which may include one or more sensors, genetic circuits, and/or electrical circuits or components. The circuitry components may be configured to detect various characteristics, such as pH, bacteria compositions, chemicals, small molecules, microRNAs, and so on. Additionally, the circuitry components may be configured to transmit data, e.g., include a data transmitter, such as a radio antenna, that allows communication between the capsule and the environment (e.g., a computing device) outside of the body. The circuitry components may be made of partially and/or entirely biodegradable material, such as from organic materials (e.g., silk derived based inks), and or the like. In some embodiments, the circuitry components may be configured to activate the capsule, such as opening or closing the capsule, as the circuitry components may be able to detect a location of the capsule and open or close the capsule at the desired location within the fluid system. In embodiments where the capsule may include communication components, the capsule may be configured to allow for in situ monitoring and sampling, which may be in addition to or separate from any sample collection. This allows the capsule to be used to monitor and report data regarding a person’s gastrointestinal tract or other biological structures in vivo, creating a patient friendly and easy to use monitoring system. The circuitry components may be inserted within the expandable material, allowing the circuitry to access the sample as the expandable material receives the sample.

[0052] In some embodiments, the capsule may be an edible element and/or an element that can be swallowed, such as a chewable, or “gummy” device, and an exterior vessel or body of the capsule may be omitted. In these instances, the electronic components may be a thin at least partially or fully biodegradable sensor with circuitry elements coupled thereto (e.g., printed onto the substrate). The expandable material may be included in the capsule to allow selective activation of certain circuitry components as the material expands after exposure to a particular volume of fluid or fluid with select characteristics, e.g., pH levels within a particular range or above or below a particular threshold. As a specific example, the capsule may include an activation mechanism activated by characteristics produced by the human body (e.g., saliva, stomach acid, etc.) or by separate materials consumed by the user, and once activated, the capsule detects biological characteristics and/or collects a sample of biological materials.

[0053] In various embodiments, the expandable material may improve the qualities of the sensing aspect of the circuitry components (e.g., improving selectivity or sensitivity) as well as improve performance of the circuitry components. For example, the expandable material may selectively allow permeation therethrough of certain chemicals, nucleic acids, or compositions, such that only select biomarkers or other compositions can travel through the expandable material to reach the circuitry components, reducing noise and acting to filter the fluids that reach the circuitry components. As another example, the expandable material may increase conductivity in response to certain fluids and be electrically connected to the circuitry components to increase or otherwise improve the charge of the circuitry components. As another example, the expandable material may have an activation and/or reactivity with a particular fluid, chemical, or composition, that enhances the detectability of the fluid, chemical, or composition by the circuitry component (e.g., assay that bonds to biomarker). The expandable material may also allow the separation of molecules by size, rather than by type. For example, the expandable material may undergo gel electrophoresis to separate the molecules based on size differences. Such separation may increase detectability of desired molecules.

[0054] In some embodiments, the capsules could be coated with polyethylene glycol to enhance surface wettability and enhance fluid flow into capsule through one or more apertures.

[0055] It should be noted that features described as being included in any single embodiment are described merely for illustrative purposes and it should be understood any of the features described herein may be implemented in any embodiment described herein. Similarly, any feature described with respect to a particular embodiment is meant as illustrative only and may be omitted.

[0056] Turning to the figures, the various embodiments will be discussed in more detail. Fig. 1 illustrates an isometric view of a capsule 100. Fig. 2 illustrates a cross-section view of the capsule of Fig. 1 taken along line 2-2 in Fig. 1. Figs. 3A and 3B illustrate views of the capsule with the coating removed and Fig. 4 illustrates an exploded view of the capsule 100 with the coating removed. With reference to Figs. 1 and 2, the capsule 100 may include a sample collection vessel 102, which may be at least partially or fully enclosed by a coating 104. The coating 104 may be configured to extend around an outer surface of the collection vessel 102. The coating 104 may be dissolvable or disintegrating and act as an outer protective layer, as well as a cover to prevent the collection vessel 102 from capturing samples until a determined location.

[0057] The coating 104 can be configured to dissolve when exposed to particular locations in the body, biological characteristics, and/or due to the presence of certain microbes, e.g., at select pH levels, after a period of time, exposure to one or more chemicals or compositions, enzymes, microorganisms, pathogens, or the like. Some examples of the coating 104 include hypromellose, hydroxyl propyl methyl, cellulose acetate phthalate, ethylcellulose, and other similar compositions. In one embodiment, the coating may be an enteric acid resistant coating that dissolves based on a relationship between coating thickness, polymer combination, and time. As one example, the coating may be similar to the Opadry EZ Swallow Film Coating System produced by Colorcon. In some embodiments, the coating 104 may include a pre or pro biotic type of casing that would allow testing of the effectiveness of a particular probiotic to a patient or user. As can be understood, the thickness of the coating 104, as well as the material, may determine the time and/or location where the coating 104 is fully dissolved.

[0058] An expandable material 112 is positioned at least partially within the capsule 100. The expandable material 112 selectively expands or otherwise activates, such as when exposed to fluid and/or select characteristics (e.g., pH levels, temperature, electricity). The expandable material 112 may also activate the sealing and/or unsealing of the capsule 100, such that a sample can be collected and the capsule 100 then sealed (e.g., isolated from the external environment). Examples of the expandable material 112 include a hydrophilic polymer or hydrogel, e.g., alginate, agarose, acrylamide, or combinations thereof. The expandable material 112 may include compounds or materials configured to generate a specific response (e.g., an immune response) in the user to encourage secretion of specific biomarkers that can then be sensed, e.g., an allergen or intolerance testing for immunoglobulin G (IgG). In some embodiments, the expandable material 112 may be encapsulated in a film that may be permeable, semi-permeable, or biodegradable to help prevent dehydration and/or delay activation.

[0059] In one example, the expandable material 112 is a hydrogel that expands upon the absorption of a fluid and in some instances expands upon exposure to a fluid within a particular range of pH levels (e.g., 5.8 to 6.2), where the pH range is selected based on the desired activation part of the fluid system, e.g., a higher pH activation level, such as above 6, may be selected to ensure that the hydrogel does not activate in the stomach which has a lower pH. In other examples, the expandable material may be activated by select enzymes, chemical(s), conductivity or electrical characteristics, microorganisms, peptides, small molecules, pathogens, or the like. For example, the expandable material 112 may be activated based on a change in electrical characteristics as ion concentrations may change at different locations with the body and/or the capsule may include an activation element that provides a charge or current to the expandable material.

[0060] In some embodiments, the expandable material 112 may be configured to be activated by a separate element (activation element), such as liquid or solid, consumed by the user shortly after or with the capsule. This activation element may then activate the expandable material 112 to cause it to expand or collapse or otherwise change in configuration. Examples of activation materials are ethylenediaminetetraacetic acid (EDTA) and glutathione (GSH). As one example, the materials may include a triggerable hydrogel such as the one described in Patent Cooperation Treaty Application No. PCT/US2017/060932, entitled “Triggerable Hydrogel Compositions and Related Methods,” filed on November 9, 2017, which is incorporated by reference herein for all purposes. It should be noted that these types of activation materials can also be used to deactivate the expandable material 112, e.g., for sample retrieval, by causing the expandable material to retract or otherwise compress.

[0061] In some embodiments, the expandable material 112 may act to collect the sample from the fluid system. For example, as the expandable material 112 selectively expands, it may absorb fluid and then the expandable material 112 can be retrieved and deactivated to release the collected fluid. In some embodiments, the expandable material 112 may capture a sample and preserve it in the same or substantially the same condition as when it was received, i.e. , the sample may not degrade or change due to the exposure to the expandable material 112.

[0062] In embodiments where the expandable material 112 is configured to collect the sample, the expandable material 112 may include characteristics to enhance the sample, such as to amplify detection of certain molecules circulating in bodily fluids. As a specific example, the expandable material may be configured to cause a molecular crowding effect of microRNAs as the molecules “crowd” or are drawn to a specific area of the expandable material 112. The expandable material 112 may have altered characteristics, such as by use of a chemical compound (e.g., polyethylene glycol (PEG)) that is combined with the expandable material 112 prior to insertion in the capsule. The altered characteristics may then define specific locations that may be more sensitive to or draw molecules thereto and/or may define certain receptors or binding sites for molecules, e.g., microRNAs. The chemical compounds used to alter the characteristics of the expandable material 112 may be deposited within the expandable material 112 in various manners, such as, for example, three dimensional printing of the expandable material 112 along with the specific chemical compounds. In some examples, macromolecular crowding may be used to positively influence cell free reactions as the macromolecules may be present at high concentrations, increasing a local effective concentration of reaction substrates.

[0063] In examples where the expandable material is a hydrogel, PEG may be deposited at specific locations within the hydrogel. This allows the microRNAs to migrate and collect in the selected locations. The crowding or collective effect may then allow the microRNAs or other molecules or components to be more readily detected by a sensor. In some embodiments, the crowding effect may also be configured to allow the sensor to read small molecules, such as microRNAs, in real time in the body, such as the Gl tract.

[0064] The collection vessel 102 is configured to capture a sample and then seal to prevent the sample from being contaminated as the capsule 100 travels through the body. In one embodiment, the collection vessel 102 includes a body 106 that defines a cavity 108. The body 106 may be formed of biodegradable, non-toxic, and/or biocompatible, and optionally injection moldable or three-dimensional printed materials, allowing ease of manufacturing, as well as to allow a user to consume the capsule 100. In some examples, the body 106 may be a polylactic acid or biocompatible photo resin, but other materials are envisioned as well and may be varied depending on the fluid system in which the capsule 100 may be used, as well as the desired manufacturing techniques. [0065] With reference to Figs. 1-4, the body 106 may be generally oval or ellipsoid shaped, but with an open top end 124. The shape of the body 106 may be configured to be smooth and without sharp angles or edges, so as to prevent irritation to a user when the capsule 100 is ingested. Similarly, the body 106 may be dimensioned to allow the user to more easily swallow the capsule 100, e.g., between 1 mm to 3 mm and preferably 2 mm long. The capsule body 106 may be dimensioned to match within standard tablet dimensions.

[0066] The body 106 may include or define an inlet port 110 in fluid communication with the cavity 108. In one embodiment, the inlet port 110 is defined on a bottom end of the body 106 and may be defined as a circular aperture. However, the inlet port 110 may be located in other areas of the body 106 and have different configurations. The inlet port 110 may allow the exit of air, fluid, and the like, from the interior of the body 106 as the fluid sample is collected and/or as the expandable material 112 expands.

[0067] The cavity 108 may extend along a length of the body 106, e.g., the body 106 may be hollow, or may extend along a portion of the length of the body 106. The size of the cavity 108 may be varied depending on the type of sample to be collected and the volume to be collected. The top end 124 or open end provides a first port or entryway into the cavity 108. [0068] In some embodiments, the body 106 may be defined in two or more portions, such as a bottom portion 134 and an upper portion 136. In these instances, the two portions 134, 136 may be coupled together to define the body 106. In other implementations, the body 106 may be formed integrally, e.g., as a single member. To this end, any component or feature discussed as being part of the upper or bottom portions may be understood to be encompassed by the body generally.

[0069] In embodiments where the body 106 includes the bottom portion 134 and the upper portion 136, the two portions 134, 136 may include mating elements. For example, a top end of the bottom portion 134 may include an engagement wall 126 extending from an interior portion of the top edge surface. In one example, the engagement wall 126 may be defined along the interior edge defining a portion of the cavity 108 and extend radially outwards along the top edge surface but terminating before reaching the outer surface of the bottom portion 134. Similarly, the upper portion 136 may include an engagement wall 130 that may extend downward from the bottom edge of the upper portion 136. The engagement wall 130 may be configured to mate with and may mirror the configuration of the engagement wall 126. For example, the engagement wall 130 may extend from the outer most perimeter edge of the top end and extend radially inward but terminate at a location before the interior most perimeter edge. In this manner, the two engagement walls 126, 130 may seat against and abut one another when the two portions 134, 136 are coupled together. However, the mating elements may be formed or defined in other manners, e.g., posts and corresponding holes, textured surfaces, or the like. The mating elements may be varied as desired, but in some embodiments, may be configured for a “push fit” type of connection, which helps to reduce complexity and easing assembly. [0070] With continued reference to Fig. 4, the upper portion 136 may include or define the top end 124 of the body 106. In some examples, the top end 124 may include a beveled or angled top edge that angles inward and downward toward a center axis of the upper portion 136. The angle or bevel may be selected to seal with a plunger assembly. The upper portion 136 may be a hollow tubular member. In some embodiments, additional sealing elements, such as, but not limited to, O-rings, U-cups, deformable materials, and the like may be included with the sealing assembly to enhance the seal. For example, in one embodiment, the top end 124 may include an O-ring coupled to an interior wall defining the passageway to the interior compartment, and this O-ring may compress against the top end of the plunger to ensure a tight seal when the capsule is sealed.

[0071] Additionally, the upper portion 136 may include a screen 132. The screen 132 may extend inwards from an interior surface of the upper portion 136 and be positioned between the top end 124 and the bottom end of the upper portion 136. The screen 132 may be defined as a planar layer that extends across a width of an interior compartment of the body 106, e.g., spans a width of the interior surface of the upper portion 136. The screen 132 may include a plunger aperture 127 through a central region thereof, the plunger aperture 127 may be defined as notched aperture within the screen 132 or more notches or steps that may engage with the outer surface of the plunger assembly. The screen 132 may also include one or more passages 156 that provide fluid communication with the cavity 108. In one embodiment, the passages 156 are defined as holes positioned along the outer edges of the screen 132 and may be spaced apart from one another. However, the passages 156 may be defined in other manners as well, including through the main body and spaced interior to the perimeter of the screen 132. In some embodiments, the screen 132 may be formed integrally with the body 106, but in other examples, may be omitted or formed separately from the body 106. For example, in some instances a mesh, semi- permeable, and/or other permeable materials may be used as the screen 132.

[0072] A sample compartment 158 or pocket may be defined by the body 106, e.g., by one or more of the upper portion 136 and bottom portion 134. In one example, the sample compartment 158 is between a bottom edge of the top end 124 and a portion of the cavity 108 in the bottom portion 134. The size of the sample compartment 158 may be varied depending on the type of sample to be collected and the volume to be collected. [0073] The capsule 100 may include a sealing assembly, such as a plunger assembly 120 (see Fig. 3A). With reference to Fig. 2, the plunger assembly 120 is configured to allow fluid into the sample compartment 158 and selectively seal to prevent additional fluid or debris from entering into the cavity 108. The plunger assembly 120 may include plunger 118 and a cap 114, which may be removably coupled together. In some embodiments, a locking assembly may be included that locks the plunger assembly in a closed position and may be activated after a fluid sample has been collected.

[0074] The plunger 118 may include a head 116, which in one embodiment may be defined as an inverted frustum, with the top facing end having a circular shape in plan view and having angled sidewalls that extend downward and inward towards a bottom end. The angled sidewalls allow a close fit and seal with the body 106. A stem 122 extends from a center of the bottom face of the head 116 and may be defined as a longitudinal extension or post. The stem 122 may include one or more longitudinal ribs or grooves that extend along a length or a portion of a length of the stem 122. The stem 122 terminates at a bottom end 144. The bottom end 144 may be defined as a securing element, such as a peg or other post that seats within the cap 114 or seal.

[0075] With reference to Fig. 4, the cap 114 may be defined as a semi-oval or elliptically shaped body having a closed bottom end, defining a curved bottom surface and a relatively planar top end. The top end of the cap 114 may include an engagement recess 146. The engagement recess 146 may be defined as a partially cylindrical aperture but other shapes are envisioned as well. The shape of the engagement recess 146 may be varied depending on the shape of the bottom end 144 of the stem 122.

[0076] With reference to Figs. 2 and 4, the capsule 100 may be assembled such that the plunger assembly 122, screen 132, and expandable material 112 are positioned at least partially within the collection vessel 102. For example, the cap 114 may be positioned within the bottom portion 134 of the body 106 of the vessel 102. The upper portion 136 may be connected or coupled to the bottom portion 134, e.g., the engagement wall 130 may seat around the engagement wall 130. The stem 122 of the plunger 118 extends through the stem or plunger aperture 127 defined by the screen 132 and the securing element or post of the bottom end of the stem 122 is received within the engagement recess 146 of the cap 114. The expandable material 112 may be received around a bottom end of the stem 122 adjacent to the cap 114. Alternatively, the expandable material 112 may be integrated into the stem 122 itself, such as forming a portion of the stem 122. In various instances, the expandable material 112 may abut against the screen 132 e.g., against a bottom surface thereof. [0077] The stem 122 may then extend through the top end 124 of the upper portion 136 and be positioned such that the head 116 is spaced apart from the top end 124 defining a gap. The coating 104 may then be applied over the stem 122 and top end 124 of the vessel 102. The coating 104 may also extend over a portion or the entirety of the outer surface of the vessel 102.

[0078] In some embodiments, the capsule 100 may also include a separate sample preservation element that helps to preserve the integrity of the sample. For example, an activation material may be stored in a separate compartment within the capsule 100 and is activated after a select volume of sample fluid has been collected. The activation material then acts to preserve the sample fluid, stopping growth or other changes, such that a “pure” sample from the location of collection can be retrieved. The activation material can be stored separately (e.g., in a compartment that is activated) or may be otherwise included in the capsule. Additionally, in some instances, the expandable or activatable material may preserve the sample in the condition as detected, e.g., in instances where the expandable material is a hydrogel the bacteria collected may be captured within the hydrogel in the same condition and characteristics as they existed when captured [0079] Figs. 5A-5E illustrate views of the capsule 100 as it is activated to collect a sample, e.g., at different points in time or locations as the capsule 100 travels through the body of a user. With reference to Fig. 5A, the capsule 100 including the coating 104, is initially swallowed or otherwise ingested by a user. In examples where the capsule 100 used to collect samples from the digestive tract, the capsule 100 travels to the stomach of the user. The coating 104 may be selected to provide protection for the capsule 100 when within the stomach, e.g., can withstand the acidic environment of a stomach, as well as seal the capsule to prevent fluids and debris from entering into the capsule 100.

[0080] With reference to Fig. 5B, the coating 104 dissolves, exposing the plunger assembly 122 and vessel 102. In one example, the coating 104 is configured to dissolve by the time the capsule 100 reaches the small intestine via natural peristaltic motion. For example, the coating 104 may be configured to dissolve based on pH specific to the small intestine or other fluid characteristics of the small intestine and/or configured to dissolve at a period of time, e.g., between 90 to 180 minutes and in some instances after 120 minutes, which may correspond to the typical travel time for the capsule to move from the mouth to the small intestine. Fluid F is then able to enter into the vessel 102. For example, the fluid F travels around the head 116 and stem 122 through the top end 124 of the body 106 and into the cavity of the upper portion 136. The fluid F then travels through the screen passages 156 of the screen 132 to reach the expandable material 112. The fluid activates the expandable material 112, causing the material to begin to expand in volume. Additionally, there may be some fluid that enters into the sample cavity 108 via the port 110, but which is expelled when the expandable material 112 is fully activated.

[0081] With reference to Fig. 5C, as the expandable material 112 is exposed to fluid, it continues to absorb and expand in volume. This expansion and increase in weight of the expandable material 112 (due to the absorption of fluid), causes the expandable material 112 to exert a downward force in direction D to be applied to the plunger assembly 120, pushing the cap 114 downward into the cavity 108 towards the bottom interior surface of the bottom portion 134 of the body 106. Additionally, fluid F continues to flow around the head 116 of the plunger 120 to reach the sample compartment 158.

[0082] With reference to Fig. 5D, as the expandable material 112 continues to absorb fluid, the downward force D continues and the expandable material 112 reaches full expansion. When fully expanded, the cap 114 is sealed against the bottom interior surface of the cavity 108, sealing the port 110 and in the process expelling any fluid that may have entered into the cavity 108 via the port 110. In many embodiments, the cap 114 is secured to the stem 122 after assembly and the stem 122 may be sufficiently long to extend fully to the bottom end of the cavity 108 and/or may include telescoping portions. That is, in one embodiment, the travel distance between the bottom surface of the head and the top surface of the body are selected to be the same distance as from the cap 114 in the open position to the bottom interior surface of the cavity 108. The downward force D may also create a slight vacuum pressure causing more fluid F to be drawn into the sample compartment 158. Further, the fluid pressure surrounding the vessel 102 may assist in exerting a force against the outer surface of the head 116 of the plunger 120, further assisting the plunger 120 to move to the sealed position.

[0083] With continued reference to Fig. 5D, in this configuration, the expandable material 112 causes the stem 122 to move sufficiently downwards that the head 116 seals against the top surface or top end 124 of the body 106. In this manner, the complementary beveled surfaces of the frustum shape of the head 116 sidewalls mates against and seats on the outer edge surface of the top surface 124. Once the top end 124 and port 110 of the vessel 102 are sealed, the fluid that flowed into the fluid compartment 158 is trapped between the bottom surface of the head 116 and the expanded material 112. In some embodiments, the capsule may also include a locking assembly that locks the plunger assembly in the closed position to further prevent inadvertent opening of the capsule as it completes traveling through the digestive tract.

[0084] With reference to Fig. 5E, once sealed, the vessel 102 may then continue through its travel through the body, e.g., through the remaining sections of the digestive tract. Due to the tight seals of the vessel, additional debris and fluid may be prevented from entering into the sample compartment. Once the vessel 102 has completed the journey, the capsule may be retrieved for example, by the user or a healthcare provider. Once retrieved, the fluid collected can be retrieved. For example, the expandable material 112 can be de activated by exposing the material 112 to an activation material or solution (e.g., using an activation material that acts to de-swell the material), allowing the capsule 100 to reopen. In other examples, the capsule 100 may be forced or “broken” by pulling the plunger assembly to an open position to otherwise accessing the interior compartment, e.g., the plunger may be activated externally by a select mechanical opening tool. In some instances, such as where the expandable material 112 swells and captures the sampled fluid, the expandable material 112 can be removed and separately analyzed to analyze the sample.

[0085] In some embodiments, the capsule 100 may not seal after the expandable material has been activated. In these instances, the expandable material 112 may be fully expanded and may not retain further fluid, and then the expandable material 112 may function as the sample compartment. Alternatively or additionally, the circuitry components may be included in the capsule 100 and may continuously sense information once activated by the expandable material and the capsule may not need to be retrieved.

[0086] With reference to Figs. 6-9D, another example of a capsule is disclosed. In this example, the capsule 200 may be similar to the first embodiment and be ingestible by a user. The capsule 200 may include a coating 204 that surrounds a portion or the entire outer surface of a vessel 202. The coating 204 may be similar to the coating 104 and be configured to selectively dissolve or disintegrate based on time, exposure to particular fluids (e.g., fluids with pH levels above or within a particular threshold or range), and the like. In one example, the coating 204 is gelatin and may include an enteric material (e.g., acid resistant material that allows movement of the capsule to the stomach or other location intact). In another example, the coating 204 may be plant based. In various examples, the coating 204 may be hypromellose without or without additional additives, coatings, or layers. The coating 204 may also be configured to dissolve within 90 minutes and/or when exposed to pH levels (e.g., approximately around pH 2) present in a stomach. However, it should be noted that in other examples, the coating 204 may be otherwise configured. For example, the coating 204 may dissolve in higher pH environments to protect from hostile or low pH in certain locations, such as the stomach.

[0087] The vessel 202 may include a body 206 that defines a hollow cavity 208. The body 206 may be formed of one or more components or portions. For example, with reference to Fig. 7, the body 206 may include a main body 214 and one or more caps 210a, 210b that connect to first and second or top and bottom ends, respectively, of the main body 214. In one example, the body 206 may be an ellipsoid or oval shaped member, with the main body 214 being a cylindrically shaped tubular member and the caps 210a, 210b being partial cylinders that taper to form an enclosed end. It should be noted that the body 206 may be formed in other manners, such as including a single cap 210a, 210b and with the main body 214 having an enclosed end and an open end. The formation of the body 206 depends on the types of manufacturing and coupling and therefore can be varied as desired, but in many embodiments may include a mechanical closing.

[0088] The main body 214 may include one or more inlet ports 216a, 216b. In one example, the inlet ports 216a, 216b may be defined as circular apertures and be positioned generally in a central area of the main body 214 and on opposite sides of the main body 214 from one another. In some embodiments, the inlet ports 216a, 216b may be aligned with one another as well, but in other embodiments may be differently configured.

[0089] In one embodiment, the main body 214 and the caps 210a, 210b include securing or mating features to allow the connection to one another. For example, the main body 214 may include a first engagement wall 218a defined on a first end of the main body 214 and a second engagement wall 218b defined on a second end, opposite of the first end. The engagement walls 218a, 218b may be defined as radially inset walls extending away from the main body 214 and positioned inwards relative to an outer perimeter of the main body 214, defining a shelf or step.

[0090] Similarly, the caps 210a, 210b may include securing or mating elements configured to mate with the main body 214. For example, each cap 210a, 210b may include a inset step 222a, 222b on its open end that is recessed below a terminal end 220a, 220b of the caps 210, 212 and extends radially inwards towards a center of the caps 210a, 210b The inset step 222a, 222b is configured to receive a portion of the main body 214 when the caps 210a, 210b are coupled to the body.

[0091] The capsule 200 may also include an expandable material 212 positioned within the vessel 202. The expandable material 212 may be substantially the same as the expandable material 112 and configured to expand in size based on the absorption of fluid. [0092] The capsule 200 may also include one or more circuitry components 230. The circuitry components 230 may include one or more sensors (e.g., biosensors, toehold sensors or switches, cell free sensors, abiotic sensors) and/or other genetic circuit elements. In one example, an abiotic sensor may be a sensor configured to sequester transcriptional and/or translation components such as that of a reporter gene (e.g., green fluorescent protein, luciferase) unless in the presence of a target analyte (e.g., microRNA). An example of this sensor can be found in PCT publication no. WO2014074648 entitled “Riboregulator Compositions and Methods of Use,” incorporated by reference herein for all purposes. In one example, the circuitry components 230 may be housed within the vessel 202 and optionally positioned within the expandable material 212. In another example, the circuitry components 230 may be housed within another location of the capsule 200, such as in one of the caps 210a, 210b.

[0093] The circuitry components 230 may be configured to detect characteristics, such as bioactivity, pH levels, pressure, temperature, peptides, inflammatory byproducts (e.g., IL-2, IL-6, gastrointestinal biomarkers, microRNAs, nucleic acids, and the like). The circuitry components 230 may biological (e.g., genetic circuits) and/or may be electronic.

[0094] The circuitry components 230 may include one or more optical sensors or be optoelectronics. In these examples, portions of the expandable material or the like may be transparent or substantially transparent to allow detection therethrough.

[0095] The capsule 200 may be assembled such that one of the caps 210a, 210b may be coupled to an end of the main body 214, e.g., cap 210b may connected to a bottom end of the main body 214, such as by inserting the cap 210 around the engagement wall 218b with the terminal end 220b of the cap 210b extending around and abutting against the engagement wall 218b and the bottom surface of the engagement wall 218b seating on the inset step 222b. Alternatively, the first cap 210a may be coupled to the main body 214 in a similar manner.

[0096] The circuitry component 230 may be inserted or embedded into the expandable material 212, e.g., the expandable material 212 may be formed around the circuitry component 230 or the circuitry component 230 may be inserted into a pocket or embedded into the expandable material 212. In some embodiments, the circuitry component 230 may be able to move freely within the capsule. In other embodiments, the circuitry component 230 may be coupled to the expandable material 212, such as by a mesh, that is positioned over the expandable material 212 or an adhesive that is securable to the expandable material 212.

[0097] With reference to Fig. 8, the expandable material 212 with the circuitry component 230 (either coupled thereto or separate) are positioned within the cavity 208 of the vessel 202. The vessel 202 may then be closed. For example, the other cap, e.g., the first cap 210a, may be coupled to a top end of the main body 214 closing the vessel 202. The coating 204 may then be positioned or applied over the vessel 202. The coating 204 may be positioned over the entire outer surface of the body 206 or may be positioned just over the ports 216a, 216b. The coating 204 may act to seal the ports 216a, 216b and the vessel 202 to prevent fluid and debris from entering into the cavity 208. The thickness of the coating 204 layer may be selected to determine the dissolution time and/or rate of the coating 204 to help ensure that the coating 204 dissolves at the appropriate time within the body. [0098] T urning to Figs. 9A-9D examples of the capsule 200 at different states as it travels through a body are disclosed. In embodiments including the circuitry components 230, the components 230 may be paired or otherwise electronically coupled with a user device or other instrument, allowing the components 230 to transmit data to the selected device after ingestion and/or after collection. For example, the components 230 may be paired through wireless communication, including, but not limited to near field communication and/or BlueTooth. After the pairing, and reference to Fig, 9A, the capsule 200 with the coating 204 applied is ingested. The coating 204 prevents fluid from entering into the cavity 208 and contacting (and thus activating) the expandable material 212. After a predetermined amount of time, e.g., 90 to 150 minutes and in some instances 120 minutes, or when the capsule 200 reaches a predetermined location within the digestive tract (e.g., based on pH levels), the coating 204 is activated to dissolve.

[0099] Once the coating 204 is dissolved or as soon as portions of the coating 204 are dissolved that cover the inlet ports 216a, 216b, fluid is able to flow into the cavity 208. For example, fluid from the digestive tract may enter the body 206 via the inlet ports 116a, 116b and in some instances the fluid pressure of the environment surrounding the capsule 200 may assist in forcing the fluid into the ports 116a, 116b. In some embodiments, the ports may be covered by a semi-permeable or other membrane that may act to filter the fluid traveling into the ports. As the fluid F enters into the cavity 208, the fluid contacts the expandable material 212, causing the expandable material 212 to be activated and increase in size. For example, as shown in Fig. 9C, the expandable material 212 increases in size, taking up more space within the cavity 208. In some embodiments, this increase may be activated at approximately 180 minutes after ingestion, and/or may be expanded within the small intestine of the user. With reference to Fig. 9D, after a predetermined amount of time and/or fluid received within the cavity 208, the expandable material 212 may be fully expanded and configured to expand to fill the cavity 208 or a substantial portion thereof. As the expandable material 212 is activated, the circuitry component 230 embedded or attached thereto is exposed to fluid and can detect various characteristics within the fluid. The circuitry component 230 may be configured to transmit information, such as via radio waves or other low powered transmission methods, to send and/or store data regarding the detected characteristics to a user device or the like.

[0100] It should be noted that in some embodiments, the expandable material may be configured to expand into only a portion of an interior cavity of the capsule. In these embodiments, other components (e.g., electrical components and sensors) may have more room for being positioned within the capsule. [0101] In some embodiments, the sample compartment of the capsule may be removable, to allow the sample to more easily be retrieved and tested. Figs. 10-13A illustrate various views of a capsule with a separate and optionally removable sample compartment. With reference to Figs. 10 and 11, the capsule 300 may include a coating 304 similar to the coatings 104, 204. The coating 304 may be applied over a portion or the entire outer surface of a vessel 302 of the capsule 300 and configured to selectively dissolve similar to the coatings 104, 204.

[0102] The capsule 300 also includes an expandable material 312, which may substantially similar to the expandable material 112, 212 and may include an circuitry component or may not include an electronic component, depending on whether a sample is to be collected and/or data to be retrieved or determined. In these embodiments, the expandable material 312 may act as a sealing assembly or sealing member to selectively seal one or more ports to the interior of the capsule.

[0103] The vessel 302 includes a body 306 that may be formed of one or more components, such as a main body 314 and a cap 310 or body portion. In this example, the capsule 300 may include a single cap 310 or body portion and the main body 314 may define a top wall 324 that acts as the cap or other enclosure for one of the ends of the body 306. The main body 314 may be defined as a generally tubular member and may be hollow with the top wall 324 defining an enclosed end for the main body 314. An open end may be defined opposite of the top wall 324 and terminate in a bottom wall 318 and may include one or more engagement walls or elements, such as an inset shelf 321 , recessed from and extending radially inward from the bottom wall 318.

[0104] One or more ports 316a, 316b may be defined in the main body 314. In one example, there may be two ports 316a, 316b defined as apertures on opposing sides of the main body 314. The ports 316a, 316b may be formed as square shaped apertures or may be otherwise configured based on the desired fluid flow into the capsule 300.

[0105] The cap 310 or bottom end of the body 306 may be formed as a cylindrical hollow member with an open end and an enclosed bottom end. The bottom end may be formed as an oval shape or otherwise rounded to assist a user in swallowing the capsule 300, e.g., may not include sharp angles or edges. The opened end of the cap 310 may include securing or retaining elements, such as engagement wall 322 that extends from a top end of the cap 310 and is positioned radially inwards from an outer perimeter of the cap 310. [0106] One or more ports 316c, 316d, 316e, 316f may be defined in the cap 310. For example, the ports 316c, 316d, 316e, 316f may be defined on the bottom enclosed end of the cap 310. The ports may be spaced irregularly or in a predetermined pattern and are sized and positioned to direct a desired fluid volume into the body 306. In other examples, the ports may be omitted.

[0107] With reference to Figs. 11 and 12, the capsule 300 may also include a sample container 350. The sample container 350 may be defined as a cylindrically shaped member with an open end and an enclosed end and defining a sample compartment 358 therein. Sample container 350 may be configured to be received within the body 306 of the vessel 302 and therefore may have a shape and dimensions that allows the container 350 to be positioned within the body 306 but move longitudinally within the body 306.

[0108] The capsule 300 may also include a cassette 301 or other housing that may include one or more circuitry elements (e.g., sensors, transmission elements, genetic circuits), or the like. The particular circuitry elements housed within the cassette 301 or circuitry housing may be substituted as desired, depending on the biological characteristics to be sensed by the capsule 300 (e.g., may be user or patient-dependent). In some embodiments, the expandable material may act as the cassette 301 to house the circuitry components and the cassette 301 may be omitted.

[0109] With continued reference to Figs. 11 and 12, the capsule 300 may be assembled such that the expandable material 312 is positioned within an interior of the cap 310 and may be positioned towards a bottom end of the cap 310. The sample container 350 may be positioned into the cap 310 such that the closed bottom end abuts or at least faces the expandable material 312. The open end of the sample container 350 may be oriented away from the expandable material 312. The main body 314 may then be coupled to the cap 310, e.g., the engagement surfaces 321, 321 may be connected together in similar manners as described above with respect to the capsules 100, 200. The main body 314 may surround the sample container 350 such that the sample container 350 is received within the main body 314. The coating 304 may then be applied to the vessel 302, either fully or in part, to cover the ports 316a, 316b, 316c, 316d, 316e, 316f. For example, the coating 304 may be applied to just the top and bottom ends of the body 306 or may be applied to the entire outer surface of the body 306.

[0110] Figs. 13A-13D illustrate various stages of the capsule 300 as it travels through a user’s body, e.g., at different points in time or locations. With reference to Fig. 13A, when the capsule 300 is initially ingested, the coating 304 is intact, preventing fluid from entering into the body 306, i.e., the ports are closed. With reference to Fig. 13B, as the coating 304 is exposed to fluid and/or fluid with select characteristics or after a predetermined period of time, the coating 304 dissolves, exposing the ports 316a, 316b, 316c, 316d, 316e, 316f. This exposure causes fluid from the digestive tract to flow into the cavity 308 via the ports 316a, 316b, 316c, 316d, 316e, 316f. [0111] With reference to Fig. 13C, as the fluid enters the cavity 308, the fluid is absorbed or otherwise activates the expandable material 312, causing the material to begin to expand in size. With the ports 316a, 316b, 316c, 316d, 316e, 316f open, and specifically the ports 316a, 316b in the main body 314 open, the fluid is then able to continue to flow into the sample container 350 and into the open end to fill the sample compartment 358.

[0112] With reference to Fig. 13D, as the expandable material 312 continues to be exposed to fluid from the ports in the cap 310, the expandable material 312 continues to expand and the force causes the sample compartment 358 to move longitudinally in direction M within the capsule 300, e.g., towards the top enclosed end of the main body 314. With reference to Fig. 13E, with the expandable material 312 fully expanded, the sample container 350 is moved to a closed position with the top end abutting a top end of the main body 314 and the walls of the sample container 350 sealing the body ports 316a, 316b preventing fluid ingress into the sample compartment 358. This seal prevents the sample fluid collected in the sample compartment 358 from being contaminated as the capsule 300 further travels through the body and exits the body. The expanded material 312 being fully expanded, to exert a sealing force against the sample container 350, e.g., clips or snaps in place.

[0113] Fig. 14 illustrates another example of a capsule 400. In this example, the capsule 400 may include a body 406 that contains an circuitry component 430 embedded or otherwise coupled thereto. In some embodiments, the circuitry component 430 may be housed on a substrate. In one example, the specific type of circuitry component 430 may be substituted with other types of circuitry components 430, which allows the circuitry elements to be changed based on the desired aspects to be sensed in a particular user, but keeping the capsule 400 otherwise the same.

[0114] In some examples, the capsule 400 may include a circuitry component 430 and a separate cassette 401 that may include one or more additional or modular circuitry components, such as one or more sensing modules (e.g., genetic circuits, bio sensors, or the like), where the cassette 401 may be removable and replaceable within the capsule 400. In these examples, the specific sensing elements or secondary circuitry components desired for a particular user may be substituted for one another by placing different cassettes 401 into the capsule 400. In this manner, certain baseline circuitry components, such as a data transmitter or the like, may not need to be reconfigured for multiple capsules, and just the specific sensing modules may be replaceable. In these examples, the genetic circuits or sensors in the cassettes 401 may further be surrounded or partially surrounded by an expandable material that may activate the genetic circuit at a predetermined time or location, e.g., the genetic circuit may be freeze dried/lyophilized and stored in the expandable material, which once expanded, hydrates the genetic circuit, activating the circuit, see, e.g., Fig. 18 discussed in more detail below.

[0115] As should be understood, multiple different circuitry components 430 may be included in the capsule 400 and are configured to be activated or otherwise detect characteristics at different locations within the fluid system, e.g., at different locations within the Gl tract. For example, various circuitry components 430 and/or sensing components may be activated in series, in a domino or cascade manner.

[0116] Optionally, an expandable material 412 may be connected to or otherwise houses the circuitry component(s) 430 or integrated therewith to selectively activate the circuitry component 430. In this example, the body 406 may be formed of a chewable “gummy” or jelly-like substance that allows a user to have an enhanced consuming experience by chewing or otherwise consuming the capsule 400. The body 406 may be shaped amorphously and in user friendly shapes, such as shaped as sweet treats, e.g., gummy bears, or the like, and may include taste enhancers, such as flavoring and sweetening. [0117] The expandable material 412 may be a biocompatible pH responsive hydrogel may include the circuitry component 430, which may be one or more genetic circuits, sensors, or the like. In another example, the expandable material 412 may be selective to an analyte, such that it expands when exposed to the analyte and/or enhances or induces crowding of molecules as discussed above. As one example, the circuity component 430 may be freeze dried within the expandable material 412 and/or on a motherboard or other substrate positioned within the body 406. In these instances, the circuity component 430 may be activated upon exposure to liquid, temperature, and/or pH sensitive conditions that act to rehydrate the circuity components 430 and detect characteristics in the bodily fluid. [0118] The expandable material 412 may also be configured to collect a charge or otherwise respond in a select manner to conduct ions, which may be used to enhance electrochemical performance of the circuitry component 430, e.g., act as an energy source for the circuitry component 430 and/or to separate analytes by size and charge.

[0119] As another example, the expandable material 412 may be configured to filter compounds or materials therethrough, such that the circuitry component 430 may receive a filtered set of biomarkers, compounds, or materials, enhancing sensitivity and accuracy of the circuitry component 430. It should be noted that in some embodiments, the expandable material 412 may function as a sensor or circuitry component itself and directly sense characteristics. For example, the expandable material 412 may be embedded with select materials (e.g., photonic crystals) that can be used as biosensors by transducing physical changes in structure to optical readouts. In this example, the expandable material 412 may be able to detect changes in mechanical forces, chemical interactions, and/or biological activity, and may be exploited to identify small molecule chemicals and metabolites, large bio-macromolecules and activity, and cellular behavior.

[0120] As another example, the expandable material 412 may be configured to activate the circuitry components 430, e.g., by providing a charge when a select volume of fluid has been absorbed or by activating certain bonds in response to the fluid that activate a genetic circuitry within the circuitry components 430.

[0121] The circuitry component 430 may be electronics (e.g., biodegradable electronics) printed on a biodegradable material, such as silk or the like, and include a sensor, battery, transducer, amplifier and/or antenna, the specific electronic elements may be varied depending on the characteristics to be detected, as well as whether the capsule is to be retrieved or biodegrade within the body or upon passing of body (i.e. , once excreted). In addition to or alternatively, the circuitry component 430 may include a genetic or biologic circuit (e.g., whole gene circuit, cell-free gene circuit, synthetic gene circuit, or other biosensors). In some examples, the circuitry component 430 may include engineered or other microorganisms (e.g., bacteria, yeast, mammalian cells, etc.) that produce a biological response after exposure to a particular compound, fluid, material, biomarker, or the like. In other words, the circuitry component 430 may include a recognition element (e.g., for analyte binding) and a transducing element (e.g., for reporting data or signals). The biological response can be converted to a digital signal and transmitted by other components within the circuity component 430 or stored.

[0122] In various implementations including electronics, the electronic component may be configured to transmit data directly to a user device (e.g., smartphone) for display, such as via an application on the user device. The user device may be any type of computing device, such as a smartphone, tablet, or wearable device. Additionally, the electronic component may transmit data to a cloud or other network, may relay the data to the user device, may transmit data to a receiver or hub device, which may then relay the data to the user device, and/or may transmit the data directly to the user device.

[0123] The expandable material 412 may also include different thicknesses and/or pH activation layers, so that certain portions of the circuitry component 430 may be activated at different times, which may correspond to different locations within the body.

[0124] Figs. 15-17J illustrate another example of a capsule that may include features described herein. The capsule 500 may be substantially similar to the other examples described herein. The capsule 500 may include a coating 502, 504, which may be similar to the coatings 104, 204. The coatings 502, 504 may be an enteric coating that selectively dissolves based on time, location, pH, or other characteristics. The coatings 502, 504 may be applied as a single layer over the entire capsule 500 or may be applied in portions, such as on a bottom and top of the capsule 500. It should be noted that the coatings may be applied in discrete positions, such as just over and surrounding the apertures or ports. [0125] With reference to Fig. 16, the capsule 500 may include a cap 506 or top portion and a container 508 or bottom portion. The top and bottom portions 506, 508 may be configured to allow ingress of fluid and biological samples, as well as optionally contain the fluid and/or biological samples obtained traveling through the Gl tract, e.g., the top and bottom portions may define a vessel. Additionally, the top and bottom portions 506, 508 may be configured to mechanically engage one another, such as through press-fit, threading, fasteners, adhesive, prongs, or the like.

[0126] The top portion 506 may define an inlet 550 that may be in fluid communication with a sample collection cavity 552 (see Fig. 17G). The inlet 550 may be defined on a top or distal end of the top portion 506 or may be located at other areas of the top portion 506, such as on the sidewalls. In some embodiments, the inlet 550 may angled or and expand in diameter as it defines an increased pathway diameter into the sample collection cavity 552. In other embodiments, the inlet 550 may have a constant diameter. The sample collection cavity 552 may be configured to receive a portion of the expandable material 512 and have a diameter or width and height sufficient to encompass an expansion of the expandable material 512 from a first size to a second size.

[0127] The bottom portion 508 of the capsule 500 may define a support structure for a pin 516 or anchoring member for the expandable material 512. In one example, the bottom portion 508 may be defined as a tubular body having a stand 518, where the stand 518 may be formed via extensions of the internal sidewalls. For example, there may be a void 554 (see Fig. 17H) on a bottom end of the bottom portion 508. The void 554 may optionally be in fluid communication with the inlet 550 of the top portion 506 to also collect samples as desired. In some embodiments, the void may be configured to receive various electronics. [0128] The stand 518 may define a pin aperture 520 therein or other structure configured to receive or otherwise support a pin 514. In some embodiments, the pin 514 may be selectively attachable to the stand 518, e.g., may be inserted and then fixed in place. [0129] The pin 514 or anchoring member 514 is configured to secure the expandable material 512 within the capsule 500. The pin 514 may include a head 516 that may be defined as a flanged area extending from a post 556. The head 516 may act to increase the surface area of the pin 514 that receives or is embedded into the expandable material 512, to help structurally support the expandable material 512 in the capsule 500. The pin 514 may include a post or leg 558 that extends from a bottom surface. The leg 558 is configured to be received in the pin aperture 520 of the stand 518. [0130] An illustrative assembly of the capsule 500 is shown in Figs. 17A-17J. With reference to Fig. 17A, a mold 530 that defines a setting cavity 532 may be used. The mold 530 may include a plug 534 or other selectively removable component that provides access to the setting cavity 532. In Fig. 17B, the expandable material 512 may be positioned in the mold 530 and in particular in the setting cavity 532 within the mold 530. For example, the expandable material 512 may be deposited in a liquid or viscous form, which causes the expandable material 512 to fill and conform to the walls of the mold 530 defining the setting cavity 532, including the plug 534. It should be noted that in some embodiments, the expandable material 512 may include a sensor or circuit, such as a genetic circuit, positioned therein, that may be positioned during the setting process or afterwards.

[0131] In some embodiments, the mold can be clear or substantially transparent. For example, in instances where the electronics or circuitry components used within the capsule may be optoelectronics (e.g., sense light), the mold may be transparent to allow the components to detect light so as to be tested or the like during formation.

[0132] With reference to Fig. 17C, the bottom portion 508 of the capsule 500 may be formed or connected. For example, the post 558 of the pin 514 may be inserted into the pin aperture 520 of the stand 518. In this example, the pin 514 may be held in place by a friction fit, but in other instances, adhesives, welding, mechanical engagement features, or the like, may be used.

[0133] With reference to Fig. 17D, the bottom portion 508, with the connected pin 514, may then be directed over the mold 530 such that the pin 514 is inserted head 516 down into the expandable material 512. In this example, the expandable material 512 may not yet have “hardened,” gelled, or set, such that the pin 514 can be inserted into the material 512, which may be a liquid or viscous to allow entry of the pin 514. The head 516 may be surrounded by the expandable material 512, to allow the material 512 to form around and embed the head 516. In some embodiments, a tool, such as a support stand 536 or mold may be used to guide the bottom portion 508 over the mold 530. For example, the support 536 may increase the surface area of the bottom portion 508 to allow easier manipulation. However, in other embodiments, the bottom portion 508 may be maneuvered directly or via other tools.

[0134] With continued reference to Fig. 17D, the mold 530 and optionally the support 536 may be used to hold the bottom portion 508 in the desired orientation relative to the mold 530 while the expandable material 512 hardens or otherwise sets. In this example, the mold 530 and support 536 help to keep the pin 514 engaged in the expandable material 512 while the expandable material 512 solidifies, e.g., stabilizes the pin 514 within the expandable material 512. [0135] With reference to Fig. 17E, in some embodiments, the entire assembly may be inverted and the mold 530 is removed. As one example, a force may be applied to the plug 534, which is transmitted to the expandable material 512, causing the expandable material 512 to release from the sidewalls of the setting cavity 532. With reference to Fig. 17F, due to the force exerted via the plug 534, the mold 530 can be removed without causing the expandable material 512 to be removed therewith, i.e., the expandable material 512 remains anchored or attached to the pin 514.

[0136] With reference to Fig. 17G, the top portion 506 of the capsule 500 may be positioned over the expandable material 512 and pin 514 and coupled to the bottom portion 508. For example, the expandable material 512 and pin 514 may be received within the sample collection cavity 552. As shown in Fig. 17G, in many embodiments, the expandable material 512 may not expand to the sidewalls of the top portion 506, such that there may be room for the expandable material 512 to expand as a sample is collected. The top portion 506 and bottom portion 508 may be coupled together, e.g., via threading or push fit, to secure the two portions 506, 508 together.

[0137] With reference to Fig. 17h, a coating 502, 504 may be applied to the top and bottom portions 506, 508. As shown in Fig. 17h, the coating 504 may enclose or cover the inlet 550 to the sample collection cavity 552, preventing ingress of fluid, debris, biologic material, and the like .

[0138] With reference to Fig. 171, in the Gl tract, the coating 502, 504 dissolves, exposing the inlet 550. A sample, such as fluid F, is then able to travel from the Gl tract (or other location within the body) into the sample collection cavity 552. As the fluid enters, the expandable material 512 expands or swells as the material reacts or collects the fluid. [0139] As shown in Fig. 17J, after a sufficient fluid F volume has been received, the expandable material 512 expands to the full size allows by the sample collection cavity 552, the expandable material 512 fills or plugs the inlet 550.

[0140] In some embodiments, various components of the capsules described herein may be optimized for storage. For example, the capsule may include sensors, such as the genetic or biologic sensors, that may be freeze dried to prevent activation and deterioration during manufacturing, storage, and transport. Then, once ready for use, may be activated. Fig. 18 illustrates a flow chart of an example method 800 for capsule assembly. The method 800 may begin with operation 802 and the genetic circuit, which may be a cell free genetic circuit, mixture is assembled. For example, the genetic circuit, such as in the form of a cell free sensor, is assembled, in some instances over ice (as to not activate the genetic circuit). The cell free sensor can either be reconstituted such that only purified recombinant proteins and ribosomes are added to the reaction, or a crude lysate in which cells are lysed and the extract clarified. Cell extracts can be generated from a variety of host organisms such as bacteria like E. coli, yeast like Saccharomyces cerevisiae and Pichia pastoris, mammalian cells like Chinese hamster ovary and HeLa, wheat germ, and tobacco. In both reconstituted and crude extract, other components are combined/added to the mixture for the activation of the sensor, such as a concentrated reaction mix that can contain nucleotides, amino acids, energy substrates, salts, molecular crowding agents, polymerases, and genetic material.

[0141] In operation 803 the hydrogel is assembled and in operation 805 is cross-linked. In some cases the hydrogel is dehydrated such that water is removed from mixture using desiccator with a temperature applied, e.g. 45°C, so as to allow better uptake of cell free in operation 804.

[0142] In operation 806, the genetic circuit is combined with the expandable material. For example, in embodiments where the expandable material is a hydrogel, the liquid hydrogel components prior to cross-linking are deposited into a portion of the capsule and all or some of the genetic circuit components are combined with the hydrogel in the portion of the capsule.

[0143] In operation 808, the genetic circuit and the expandable material is combined to allow uptake of genetic circuit by expandable material. Additionally, the combination may be positioned on ice or otherwise cooled so as to not activate the genetic circuit.

[0144] In operation 8, the capsule with the genetic circuit and the expandable material is freeze dried / lyophilized. For example, the materials may be exposed to a quick drop in temperature, and subsequent sublimation of the remaining ice which acts to preserve the genetic sensors and the expandable material. In some embodiments, the expandable material and the genetic circuit may be combined together outside of the capsule, then exposed to the freeze drying operation, and then can be inserted at later time in the desired capsule components.

[0145] In operation 812, the capsule components are assembled together with the genetic circuit and expandable material. Utilizing method 800, the capsule may have an extended shelf life, such as it can last up to 9 months or more, without significant degradation.

[0146] The foregoing description has a broad application. For example, while examples disclosed herein may focus on capsules that travel through the digestive tract, it should be appreciated that the concepts disclosed herein may equally apply to other types of medical monitoring or sampling, including embedded sensors. For example, certain sensing and activation may occur before a user actually swallows the device, e.g., in a user’s mouth where the saliva can activate the various components.

[0147] It should be noted that the capsule embodiments described herein are meant to be fully modular and any component of any particular design, embodiment, for example, can be added into or removed from the various embodiments, as desired. For example, while many of the capsules may include a separate cassette or circuitry housing, in other instances, the expandable material may function as the circuitry housing and the cassette may be omitted. As another example, in some instances the capsules may both collect a sample and detect data (e.g., include a circuitry component), but in other instances the capsules may collect a sample or detect data. In instances where no sample is collected, the capsule may still open and close as described, such activation is meant to allow exposure of the circuitry component to fluid at a particular location within the fluid system and/or selectively of sensors, and the capsule may not be further retrieved or the like, rather the data may be transmitted to a user device by the circuitry components.

[0148] As another example, the capsules described herein can be used for non-biological fluid systems where data collection and/or sampling is desired. As specific example, energy reactors may need to determine information of fluid (e.g., radioactive fluid) at different locations and the capsule could be configured to be activated at the desired location within the fluid system of the energy reactor. Other fluid systems, such as chemical plants, manufacturing plants, and the like may also use the capsules and other techniques described herein. Further, for biological systems, it should be understood that the techniques may be used with various types of animals where digestive and other bodily characteristics may need to be sampled or tested, such as to improve medical care, environmental indicators (e.g., early warning of pandemic conditions), or for scientific reasons.

[0149] The above specification, examples and data provide a complete description of the structure and use of exemplary embodiments of the invention as defined in the claims. Although various embodiments of the claimed invention have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, it is appreciated that numerous alterations to the disclosed embodiments without departing from the spirit or scope of the claimed invention may be possible. Other embodiments are therefore contemplated. It is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative only of particular embodiments and not limiting. Changes in detail or structure may be made without departing from the basic elements of the invention as defined in the following claims.

Claims

1. An ingestible capsule comprising: a selectively expandable material; and a genetic circuit positioned within the selectively expandable material, wherein the selective expansion of the selectively expandable material exposes the genetic circuit to bodily molecules or fluids at a predicable location within the gastrointestinal tract.

2. The ingestible capsule of claim 1, wherein the expandable material is a hydrogel.

3. The ingestible capsule of any of the preceding claim, wherein the genetic circuit is a cell free system.

4. The ingestible capsule of any of the preceding claims, wherein the expandable material is configured to crowd selected bodily molecules to enhance detectability of the selected bodily molecules by the genetic circuit.

5. The ingestible capsule of claim 4, wherein the bodily molecules are biomarkers.

6. The ingestible capsule of any of the preceding claims, wherein the expandable material preserves the bodily molecules or fluids.

7. The ingestible capsule of any of the preceding claims, wherein the genetic circuit transmits data to an external device while positioned within the gastrointestinal tract.

8. The ingestible capsule of any of the preceding claims, wherein the genetic circuit provides in vivo data collection.

9. An ingestible capsule comprising: a vessel comprising: an expandable material positioned within the vessel; and a sealing assembly moved from an open position to a sealed position upon expansion of the expandable material; and a coating positioned over a portion of the vessel and configured to selectively dissolve to expose one or more inlets into the vessel.

10. The ingestible capsule of claim 9, wherein the sealing assembly comprises: a plunger; and a cap coupled to the plunger, wherein as the expandable material expands, the plunger moves to seal around an open end of the vessel.

11. The ingestible capsule of any of claims 9 or 10, wherein the vessel defines a sample compartment configured to receive fluid from outside of the vessel, wherein in the sealed position, the sealing assembly prevents fluid from entering or exiting the sample compartment.

12. The ingestible capsule of any of claims 9-11 , wherein the sealing assembly comprises a sample container configured to move longitudinally within the vessel.

13. The ingestible capsule of any of claims 9-12, further comprising a genetic circuit for detecting and optionally transmitting data regarding characteristics of a sample received within the vessel.

14. An ingestible capsule comprising: a coating; a body defining a cavity therein and comprising a port in fluid communication with the cavity; and an expandable material positioned within the cavity, wherein in a first state, the expandable material is positioned to allow fluid communication between the port and the cavity; and in a second state, the expandable material is positioned to prevent fluid communication between the port and the cavity.

15. The ingestible capsule of claim 14, wherein the expandable material is a hydrogel and the first state is unexpanded and in the second state is expanded.

16. The ingestible capsule of any of claims 14 or 15, further comprising an circuitry component positioned within the body and configured to detect one or more characteristics of fluid received within the cavity.

17. A capsule comprising: a hydrophilic polymer; and a circuitry component positioned within the hydrophilic polymer.

18. The capsule of claim 17, wherein the hydrophilic polymer activates the circuitry component.

19. The capsule of any of claims 17 or 18, wherein the hydrophilic polymer increases a sensitivity of the circuitry component.