CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent

Application No. 62/833,890, filed April 15, 2019, titled“Ingestible Capsules for Sampling Intestinal Contents,” the entirety of which is hereby incorporated by reference.

FIELD

[0002] The present application generally relates to sampling contents of a patient’s gastro-intestinal contents, and more specifically relates to ingestible capsules for sampling intestinal contents.

BACKGROUND

[0003] Sampling the contents of a patient’s small intestines can be a complicated and difficult process. Typically, the patient is anesthetized and either an endoscope or a proctoscope is inserted into the patient. The tool is then snaked through the patient’s gastro-intestinal tract to the small intestines, where a sample of the small intestines’ contents can be obtained and retrieved. Such a process, however, is extremely invasive, requires a general anesthesia, and requires the patient make and attend an appointment at a hospital, clinic, or other medical facility.

SUMMARY

[0004] Various examples are described for ingestible capsules for sampling intestinal contents. One example device includes a capsule housing defining an interior cavity and a plurality of inlet ports; a piston disposed within the interior cavity and proximate to a first end of the capsule housing, the piston configured to seal an inner perimeter of the interior cavity to prevent movement of material past the piston; a biasing element positioned between within the interior cavity and between the piston and the first end of the cavity, the spring in at least a partially compressed state; an enteric material disposed within the interior cavity, the enteric material positioned between the piston and a second end of the cavity, the second end opposite the first end, the enteric material positioned to prevent movement of the piston by the biasing element towards the second end of the cavity; a one-way valve positioned at a first end of the cavity and sealing a first inlet port of the plurality of inlet ports; wherein the capsule housing defines a second inlet port exposing the enteric material to an external environment.

[0005] Another example device includes a capsule housing defining an interior cavity and a plurality of inlet ports; a super-absorbent polymer (“SAP”) disposed within the interior cavity, the SAP configured to swell in response to absorbing a fluid; and an enteric material coating the capsule housing and entirely obstructing at least one inlet port of the plurality of inlet ports; wherein the SAP is positioned to entirely obstruct the at least one inlet port of the plurality of inlet ports after swelling.

[0006] A further example device includes a capsule housing defining an interior cavity and a plurality of inlet ports, the capsule housing comprising first and second portions slidably coupled to each other to define the interior cavity; a biasing element coupled to the first portion of the capsule housing at a first end of the interior cavity, the biasing element further coupled to a piston disposed within the interior cavity; an enteric material disposed in the interior cavity and coupled to a second end of the interior cavity, the second end opposite the first end; a super-absorbent polymer (“SAP”) disposed in the interior cavity at the first end of the interior cavity and exposed to an exterior environment by at least one inlet port of the plurality of inlet ports, the SAP positioned in a gap between the first and second portions of the capsule housing and configured to swell and expand the gap by sliding the first and second portions of the capsule housing with respect to each other; wherein the piston is coupled to an enteric material to stretch the biasing element; wherein expanding the gap by the SAP opens one or more inlet ports of the plurality of inlet ports to expose the enteric material to the exterior environment.

[0007] Another example device includes a capsule housing defining an interior cavity and a least one inlet port; a one-way valve positioned in the at least one inlet port; an enteric material entirely covering the at least one inlet port; wherein a gas pressure within the interior cavity provides a partial vacuum.

[0008] These illustrative examples are mentioned not to limit or define the scope of this disclosure, but rather to provide examples to aid understanding thereof. Illustrative examples are discussed in the Detailed Description, which provides further description. Advantages offered by various examples may be further understood by examining this specification. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The accompanying drawings, which are incorporated into and constitute a part of this specification, illustrate one or more certain examples and, together with the description of the example, serve to explain the principles and implementations of the certain examples.

[0010] Figures 1A-1C show an example ingestible capsule for sampling intestinal contents;

[0011] Figures 2A-2B show an example ingestible capsule for sampling intestinal contents;

[0012] Figure 3 shows an example ingestible capsule for sampling intestinal contents;

[0013] Figures 4A-4C show an example ingestible capsule for sampling intestinal contents;

[0014] Figures 5A-5D show an example ingestible capsule for sampling intestinal contents;

[0015] Figures 6A-6C show an example ingestible capsule for sampling intestinal contents;

[0016] Figures 7A-7D show an example ingestible capsule for sampling intestinal contents;

[0017] Figures 8A-8B show an example ingestible capsule for sampling intestinal contents;

[0018] Figures 9A-9F show an example ingestible capsule for sampling intestinal contents;

[0019] Figures 10A-10B show an example ingestible capsule for sampling intestinal contents;

[0020] Figures 11A-11B show an example ingestible capsule for sampling intestinal contents;

[0021] Figures 12A-12B show an example ingestible capsule for sampling intestinal contents; and

[0022] Figures 13A-13C show an example ingestible capsule for sampling intestinal contents.

DETAILED DESCRIPTION

[0023] Examples are described herein in the context of ingestible capsules for sampling intestinal contents. Those of ordinary skill in the art will realize that the following description is illustrative only and is not intended to be in any way limiting. Reference will now be made in detail to implementations of examples as illustrated in the accompanying drawings. The same reference indicators will be used throughout the drawings and the following description to refer to the same or like items.

[0024] In the interest of clarity, not all of the routine features of the examples described herein are shown and described. It will, of course, be appreciated that in the development of any such actual implementation, numerous implementation-specific decisions must be made in order to achieve the developer’s specific goals, such as compliance with application- and business- related constraints, and that these specific goals will vary from one

implementation to another and from one developer to another.

[0025] To sample a patient’s intestinal contents, a doctor obtains an ingestible capsule that has been configured to open within the patient’s small intestines, sample a quantity of the contents, and re-seal itself while retaining the sample. The capsule then passes through the remainder of the patient’s intestines and can be recovered from the patient’s stool.

[0026] In this example, the capsule is shaped like a pill with an elongated body and rounded end caps. Each end cap has an opening that can expose an interior cavity of the capsule to the external environment. A one-way valve is positioned in one of the openings and is biased to a closed position. To block the second opening, a capsule of enteric material is positioned within the interior cavity with one end of the enteric capsule pressed against and sealing the second opening. The enteric capsule is formed from a material that is stable within the acidic environment of the stomach, but which dissolves in the higher-pH environment of the small intestine.

[0027] Also within the interior cavity is a piston and a spring. The piston and spring are pressed against the first end of the interior cavity, near the one way value. The spring is compressed and held in place by the piston, which in turn is held in place by the enteric capsule. Thus, the enteric capsule holds the piston in place against the compressed spring.

[0028] This arrangement seals the interior cavity of the capsule via the one-way valve and the enteric capsule, which block the corresponding openings into the interior cavity. After the patient swallows the capsule, it travels to the stomach, where it retains its initial configuration. However, after passing out of the stomach and into the small intestine, the enteric material begins to dissolve, which allows the spring to begin to expand and press the piston towards the opposite end of the interior cavity. This movement generates a negative pressure between the piston and the one-way valve, which opens the one-way valve and draws material from the small intestines into the cavity.

[0029] As the enteric capsule continues to dissolve, the spring continues to force the piston towards the opposite end of the cavity, drawing in additional material from the small intestines. At some time later, the piston reaches the opposite end of the interior cavity and the pressure between the piston and the one-way valve equalizes, and the one-way valve closes, sealing the interior cavity of the capsule. The capsule then progresses through the remainder of the intestinal tract and is later retrieved from the patient’s stool sample. The capsule can then be opened and its contents analyzed.

[0030] The use of such a capsule allows a doctor to retrieve a sample of a patient’s intestinal contents without resorting to an invasive medical procedure. Instead, the patient simply swallows the capsule as she would any pill. Further, because the enteric material only begins to dissolve in the small intestines, the capsule is able to sample only the desired material.

[0031] This illustrative example is given to introduce the reader to the general subject matter discussed herein and the disclosure is not limited to this example. The following sections describe various additional non-limiting examples and examples of ingestible capsules for sampling intestinal contents.

[0032] Referring now to Figures 1A-1C, Figures 1A-1C show a cross- section of an example capsule 100 for sampling gastro-intestinal contents. Figure 1A illustrates the example capsule 100 before it has been ingested. In this example, the capsule 100 has a capsule housing 110 that, in this example, forms a hollow cylinder with a circular cross-section. It should be appreciated that any suitable shape may be employed to form the capsule housing 110. Further, in this example, the capsule housing is sized according to the commercial capsule size 00, having a diameter of substantially 9.5 millimeters (“mm”) and a length of substantially 22 mm (including the end caps discussed below). In some examples, the capsule housing 110 may be sized to hold a minimum volume, such as at least 200 microliters, or at least 300 microliters. In some examples 200 microliters of fluid may be the minimum amount necessary to obtain a usable quantity of DNA or RNA for analysis; however, a larger quantity, e.g., 250 or 300 microliters, may be desirable to help ensure sufficient material is captured. [0033] In this example, the capsule housing 110 is formed of a suitable

FDA-approved polycarbonate material. In some examples, suitable materials may include an additive to reduce surface friction to allow the capsule to more easily traverse the patient’s gastro-intestinal tract, such as a ProPell low friction compound available from Foster.. In some examples, it may be desirable to construct the ingestible capsule of a material that will biodegrade over a time period of several weeks or more. For example, in some instances, a capsule may become lodged in a patient’s intestinal tract. Retrieving such a capsule may require an invasive procedure, up to and including surgery. Thus, if the capsule housing 110 is constructed from a biodegradable material, such as a polyvinyl alcohol (“PVA”), the capsule housing 110 may simply degrade within the small or large intestines obviating the need for a procedure to retrieve the capsule 100.

[0034] Each end of the capsule housing 110 is sealed with an end cap made of an enteric material 130. An enteric material is one that dissolves within solutions that have a pH greater than that typically found in the stomach. For example, suitable enteric materials may dissolve in solutions having a pH above 8. Further, it should be appreciated that different enteric materials may be employed depending on where within the intestinal tract a sample is desired. For example, some enteric materials, e.g., Eudragit L 100-55 (methacrylic acid and ethyl acrylate co-polymer), may dissolve within the small intestines, while others may remain intact until reaching the environment within the large intestines, such as Eudragit S 100. Further, if sampling of patient’s stomach contents is desired, a material that dissolves in stomach acid may be used. However, in this example, the end caps are formed from an enteric material 130 that is designed to dissolve within the small intestines.

[0035] In addition, a quantity of a super-absorbent polymer (“SAP”) 120 is positioned at the two ends of the capsule housing 110 and are sealed within the interior cavity of the capsule housing 110 by the enteric material 130. A SAP is a polymer that swells when it absorbs water. Any suitable SAP may be employed, such as sodium polyacrylate, a polyacrylamide hydrogel, etc. In this example the SAP 120 is deposited around the inner perimeter of each end of the capsule housing, thereby forming a ring. However, in some examples, the SAP 120 may be deposited only in one or more locations at each end of the capsule housing. [0036] The configuration of the ingestible capsule 100 shown in Figure 1A is the ingestible capsule 100 prior to ingestion by a patient, or while the capsule 100 traverses the patient’s stomach prior to reaching the small intestines.

[0037] Once the capsule reaches the small intestines, the end caps 130 begin to dissolve exposing the interior of the capsule housing 110 and thereby allowing material within the small intestines to flow into the interior cavity. This configuration is shown in Figure IB, where material 140 from the patient’s small intestines has flowed into the capsule 100.

[0038] In addition, when fluid within the patient’s small intestines encounters the SAP 120, the SAP 120 begins to swell and ultimately entirely obstructs the openings into the interior cavity, sealing the material 140 within the capsule housing 110 as shown in Figure 1C. The capsule 100 may then continue to pass through the patient’s intestinal tract until it can be retrieved from the patient’s stool.

[0039] It should be appreciated that while the configuration shown in

Figures 1A-1C employed enteric end caps 130 configured to dissolve in a patient’s small intestine, using a different material may allow sampling of contents within different portions of the patient’s gastro-intestinal tract. For example an enteric material configured to degrade in a patient’s large intestines may allow sampling of material from the large intestine using the mechanism discussed above.

Similarly, a material that degrades within the patient’s stomach may allow sampling of such contents.

[0040] Further, and while not illustrated in Figures 1A-1C, in some examples, a dissolvable dye may be included within the capsule 100 and sealed with a second enteric material. As discussed above with respect to other example capsules, the second enteric material may dissolve within the patient’s large intestines, releasing the dye, allowing the capsule 100 to be more easily retrieved from the patient’s stool.

[0041] Referring now to Figures 2A-2B, Figures 2A-2B show an example ingestible capsule 200 for sampling gastro-intestinal contents. Figure 2A illustrates the example capsule 200 before it has been ingested. In this example, the capsule 200 has a capsule housing 210 that defines an interior cavity in which gastro-intestinal contents may be captured. In this example, the capsule housing has an inlet ports 212 defined at one end of the capsule 200. A one-way value 220 is positioned to block the inlet port 212 to allow material to enter the inlet capsule 200, but prevent such material from escaping the capsule 200. In this example, the one-way valve is a duckbill valve; however, any suitable one way valve may be employed, such as a ball check valve or an umbrella valve.

[0042] In addition, the capsule 200 is coated with an enteric material 230, which covers the inlet port 212. In addition, a second type of enteric material 260 is used to coat the end of the capsule 200 opposite the inlet port 212. The second type of enteric material 260 is designed to survive within a patient’s small intestine, but to degrade in the large intestine. It is used to cover a dissolvable dye 250.

[0043] In this example, the capsule housing 210 encloses an interior cavity that has a gas pressure having a partial vacuum, i.e., the gas pressure within the capsule 100 is less than a standard atmospheric pressure. This partial vacuum causes external pressure applied to the one-way valve 220 to open the one-way valve 220 and allow material to pass through the value, thereby capturing such material within the capsule. However, because the inlet port 212 is initially covered by the enteric material 230, the one-way valve remains closed.

[0044] Figure 2B illustrates the capsule 200 after it has been ingested and passed into the patient’s small intestine. The enteric material 230 has degraded, exposing the capsule housing 210 and the inlet port 212 to the external environment. Further, the partial vacuum within the capsule 200 has drawn material 240 into the capsule 200 through the duckbill valve 220, filling the capsule with a sample of the patient’s intestinal contents. Once the capsule 200 is filled, or the partial vacuum has equalized with the external air or fluid pressure, the duckbill valve 220 closes, sealing the contents within the capsule 200. The capsule 200 may then traverse the remainder of the small intestine and enter the large intestine.

[0045] Within the large intestine, the second enteric material 260 degrades, releasing the dissolvable dye 250 into the large intestines. The dye 250 may dye the intestinal contents surrounding the capsule, which may aid in identifying the location of the capsule 200 in the patient’s stool. At which time, the capsule may be retrieved. It should be appreciated that while in some examples, the enteric material 230 encapsulating the capsule housing 210 is configured to degrade within a patient’s small intestines, and thus may be a different material than the second enteric material 260, in some examples, both portions of enteric material 230, 260 may be the same, e.g., configured to dissolve within the patient’s large intestines.

[0046] As discussed above with respect to Figures 1A-1C, the capsule may be constructed of any suitable FDA-approved polycarbonate material, potentially with an additive (or additives) to lower the surface frictional coefficient to allow easier passage through the patient’s intestinal tract. Further, the capsule 200 may be constructed of a PVA or other biodegradable material for the reasons discussed above. In some examples, it may be desirable to construct all components of the capsule 200 of a biodegradable material so that the entire capsule degrades in case it becomes lodged within the patient’s gastro-intestinal tract, rather than just the capsule housing 210 itself. Thus, the entire capsule 200 may degrade. However, in some examples, the capsule housing 210 itself may be the largest component and thus, if it degrades, the other portions of the capsule may safely pass through the patient’s gastro-intestinal tract. Thus, in some examples, only some portions of the capsule may be constructed from a PVA or other biodegradable material.

[0047] It should be appreciated that, while the example shown in Figures

2A-2B includes a dissolvable dye and second enteric coating, such features are optional and may be omitted. However, such features may allow the capsule 200 to be more easily identified within the patient’s stool.

[0048] In addition, the capsule 200 in this example is sized to capture at least 200 microliters of material, though in some examples, it may be sized to capture 250 or 300 microliters to help ensure that sufficient material is captured, even if the entire cavity is not filled.

[0049] Figure 3 shows an example ingestible capsule 300 similar to the capsule 200 shown in Figures 2A-2B; however, the example shown in Figure 3 employs an umbrella valve 320 rather than a duckbill valve 220. As with the example shown in Figures 2A-2B, the capsule 300 has a capsule housing 310, which defines an interior cavity, containing a partial vacuum, and an inlet port 312. The umbrella valve 320 seals the inlet port 312 once the interior pressure within the cavity has equalized with the exterior pressure. In addition, the capsule 300 includes a dissolvable dye 350 that is covered with a second enteric coating 360 that dissolves within a patient’s large intestine. Further, as discussed above with respect to Figures 2A-2B, the capsule 300 in this example is sized to capture at least 200 microliters of material, though in some examples, it may be sized to capture 250 or 300 microliters to help ensure that sufficient material is captured, even if the entire cavity is not filled.

[0050] Referring now to Figures 4A-4C, Figures 4A-4C show an example ingestible capsule 400 for sampling gastro-intestinal contents. Figure 4A illustrates the capsule 400 before it has been ingested. In this example, the capsule 400 has a capsule housing 410 that defines an interior cavity and multiple inlet ports 412, 414. One set of inlet ports 412 is formed in one end of the capsule housing 410, while an additional set of inlet ports 414 is formed around the perimeter of the capsule housing 410. A quantity of a SAP 420 is positioned at one end of the cavity to absorb liquid flowing in from the inlet ports and the swell into the cavity, as will be discussed in more detail below. Further, in this example, the interior cavity has been primed with a partial vacuum, as discussed above with respect to Figures 2A-2B; however, the presence of the enteric coating 430 prevents the pressure within the cavity from equalizing with the surrounding environment.

[0051] An enteric coating 430, which is configured to degrade within the small intestine, encases the capsule 400, while a dissolvable dye is positioned at an end of the capsule opposite the first set of inlet ports 412. The dissolvable dye is covered by a second enteric material that is configured to degrade within the patient’s large intestine.

[0052] As discussed above, the capsule 400 may be constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule may be constructed of such a biodegradable material to allow part or all of the capsule 400 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract. Further, any suitable SAP may be employed, such as those discussed above with respect to Figures 1A-1C.

[0053] Figure 4B illustrates the example capsule 400 after the enteric material 430 has degraded, exposing the sets of inlet ports 412, 414. The partial vacuum within the capsule 400 has drawn material 440 from the environment into the capsule 400. In addition, as fluid has entered the capsule 400, the SAP 420 has begun to swell and fill a portion of the capsule’s interior cavity.

[0054] Figure 4C illustrates the capsule 400 after the SAP 420 has swelled and blocked both sets of inlet ports 412, 414, thereby sealing the interior cavity and capturing the material 440 from the patient’s small intestines. The capsule 400 will continue to traverse the patient’s intestinal tract until arriving at the large intestine, where the second type of enteric material 460 will degrade, exposing the dissolvable dye 450. As discussed above with respect to Figures 2A- 2B, the use of the dye 450 and second enteric coating 460 is optional, but it may allow the patient or medical personnel to more easily locate the capsule within the patient’s stool. It should be appreciated that while in some examples, the enteric material 430 encapsulating the capsule housing 410 is configured to degrade within a patient’s small intestines, and thus may be a different material than the second enteric material 460, in some examples, both portions of enteric material 430, 460 may be the same, e.g., configured to dissolve within the patient’s large intestines.

[0055] As discussed above with respect to other examples, the capsule 400 in this example is sized to capture at least 200 microliters of material, though in some examples, it may be sized to capture 250 or 300 microliters to help ensure that sufficient material is captured, even if the entire interior cavity is not filled.

[0056] Referring now to Figures 5A-5D, Figures 5A-5D show an example ingestible capsule 500 for sampling gastro-intestinal contents. Figure 5A illustrates the example capsule 500 before it has been ingested. In this example, the capsule 500 has a capsule housing 510, which defines an interior cavity in which material may be captured. As discussed above, the capsule housing may be constructed of any suitable material, such as an FDA-approved polycarbonate material. Such a material may be further modified with a friction-reducing material.

[0057] The capsule housing 510 also defines multiple sets of inlet ports

512, 514 and, as with examples discussed above, contains a partial vacuum. An enteric material 530 is positioned over one set of inlet ports 512, but the second, though in some examples, the enteric material may cover both sets of inlet ports 512, 514. A piston 514 is positioned within the housing and at one end of the cavity, thereby blocking the second set of inlet ports 514. A quantity of SAP 520 is positioned between the piston 540 and the end of the capsule housing 510 so that when the SAP 520 expands, it presses the piston 540 towards the opposite end of the cavity.

[0058] The sets of inlet ports 512, 514 provide two different sets of openings into the interior cavity. The first set of inlet ports 512 at one end of the capsule exposes the SAP 520 to the exterior environment allowing material to enter the inlet port(s) 512 and interact with the SAP 520, causing it to expand. The second set of inlet ports 514 provides access to the interior cavity where a sample of the intestinal contents may be captured. However, the initial position of the piston 540 obstructs the second set of inlet ports 514.

[0059] Figure 5B illustrates the piston 540 employed in this example. As can be seen, the piston 540 has upper and lower portions 542, 544 that engage with the interior walls of the capsule housing 510 and prevent movement of material around the edges of the piston 540. The upper portion 542 of the piston is positioned near the SAP at one end of the interior cavity and engages with and seals the interior perimeter of the capsule housing 510, while the lower portion 544 also engages with and seals the interior perimeter of the capsule housing 510 and blocks the second set of inlet ports 514. And while the lower portion 544 engages with the interior of the capsule housing 510 to block the inlet ports 514, the lower portion 544 also defines openings 546 to allow material to pass through. These openings 546 may allow fluid or other material to travel through the piston and into the interior cavity to be captured. And while multiple openings 546 are shown in this example, any suitable number of openings may be employed, including as few as one.

[0060] Referring now to Figure 5C, Figure 5C illustrates the example capsule 500 after the enteric material 530 has degraded and the SAP 520 has begun to expand. As the SAP 520 expands, it presses the piston 540 towards the opposite end of the interior cavity, thereby opening the second set of inlet ports 514. Once the second set of inlet ports 514 have been opened, the partial vacuum within the interior cavity draws material 570 into the cavity from the exterior environment and through the openings 546 defined in the piston 540.

[0061] Referring to Figure 5D, as the SAP 520 continues to expand, it continues to drive the piston 540 across the cavity until the upper portion 542 of the piston 540 obstructs the second set of inlet ports 514, thereby sealing the interior cavity and the captured material 570. The capsule 500 will continue to traverse the patient’s intestinal tract until arriving at the large intestine, where the second type of enteric material 560 will degrade, exposing the dissolvable dye 550.

[0062] As discussed above with respect to Figures 2A-2B, the use of the dye and second enteric coating is optional, but it may allow the patient or medical personnel to more easily locate the capsule within the patient’s stool. It should be appreciated that while in some examples, the enteric material 530 covering the set of inlet ports 512 is configured to degrade within a patient’s small intestines, and thus may be a different material than the second enteric material 560, in some examples, both portions of enteric material 530, 560 may be the same, e.g., configured to dissolve within the patient’s large intestines. Further, and as discussed above with respect to other examples, the capsule 500 in this example is sized to capture at least 200 microliters of material, though in some examples, it may be sized to capture 250 or 300 microliters to help ensure that sufficient material is captured, even if the entire interior cavity is not filled.

[0063] Example capsules, such as the capsule 500 shown in Figures 5A-

5D, may be constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule may be constructed of such a biodegradable material to allow part or all of the capsule 500 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract.

Further, any suitable SAP may be employed, such as those discussed above.

[0064] Referring now to Figures 6A-6C, Figures 6A-6C show an example ingestible capsule 600 for sampling intestinal contents. Figure 6A illustrates the capsule 600 before it has been ingested. The example shown in Figure 6A is similar the example shown in Figures 5A-5C in that it includes a capsule housing 610 defining an interior cavity, and employs a SAP 620 and a piston 640 to selectively open a set of inlet ports 614 to capture material. In this example, the capsule housing 610 is constructed from an FDA- approved polycarbonate material that includes a further material to reduce its surface friction to enable easier travel through a patient’s gastro-intestinal tract.

[0065] One end of the capsule housing 610 defines a set of inlet ports 612 that is initially covered by a layer of enteric material 630. Once the enteric material 630 has degraded in the patient’s intestines, material may traverse the inlet port(s) 612 and interact with the SAP 620, causing it to swell.

[0066] The second end of the capsule housing 610 has a quantity of dissolvable dye 650 covered by a second enteric material 660. The second enteric material 660 is configured to degrade within a patient’s large intestine, exposing the dye. It should be appreciated that while in some examples, the enteric material 630 covering the set of inlet ports 612 is configured to degrade within a patient’s small intestines, and thus may be a different material than the second enteric material, in some examples, both portions of enteric material may be the same, e.g., configured to dissolve within the patient’s large intestines.

[0067] The piston 640 disposed within the cavity is similar in design to that shown in Figures 5B, however, the piston in 640 also includes a protrusion that extends from the lower portion of the piston 640 towards the second end of the capsule housing 610. In this example, rather than the entire interior cavity containing a partial vacuum, a membrane 670 subdivides the interior cavity and maintains a partial vacuum between the membrane 670 and the second end of the interior cavity.

[0068] Referring now to Figure 6B, when the piston 640 traverses the interior cavity due to expansion of the SAP 620, the piston’s protrusion pierces the membrane 670, which creates a pressure differential causing material 680 to be drawn into the capsule 600, through inlet ports 614 and the openings in the piston 640. Further, as with the example shown in Figures 5A-5D, once the piston 640 has reached the limit of travel within the cavity, the upper portion of the piston blocks the set of inlet ports 614, sealing the captured material 680 within the capsule 600.

[0069] The example shown in Figures 6A-6C may be advantageous because the partial vacuum is contained separately from the piston 640, thereby reducing the chance the piston 640 may be prematurely drawn from its initial position by the partial vacuum. Further, and as discussed above with respect to other examples, the capsule 600 in this example is sized to capture at least 200 microliters of material, including within the region initially sealed by the membrane 670, though in some examples, the interior cavity may be sized to capture 250 or 300 microliters to help ensure that sufficient material is captured, even if the entire interior cavity is not filled.

[0070] Example capsules, such as the capsule 600 shown in Figures 6A-

6C, may be constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule may be constructed of such a biodegradable material to allow part or all of the capsule 600 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract.

Further, any suitable SAP may be employed, such as those discussed above.

[0071] Referring now to Figures 7A-7D, Figures 7A-7D show an example ingestible capsule 700 for sampling intestinal contents. Figure 7A illustrates the example capsule 700 before it is ingested. In this example, the capsule 700 has two capsule housing portions 710, 711 that together define an interior cavity and are configured to slide with respect to each other. The two capsule housing portions 710, 711 are constructed of an FDA-approved polycarbonate, which has an additional material configured to reduce the sliding friction of the capsule 700.

[0072] The first capsule housing portion 710 defines a first set of inlet ports 712 that expose a SAP 720 to an exterior environment. The second capsule housing portion 711 defines a second set of inlet ports 714 that are initially obstructed by the first capsule housing portion 712. As will be described below, the first capsule housing portion 710 slides to open the second set of inlet ports 714, allowing material from an exterior environment to enter the interior cavity.

[0073] A piston 740 is positioned within the interior cavity and is coupled to a spring 730 or other suitable biasing member. The other end of the piston 740 is coupled to an enteric material 750 that is also coupled to the second end of the capsule 700. The spring 730 is initially extended and exerts a force on the piston 740 tending to pull it towards the first end of the capsule 700, but the piston 740 is held in place by the enteric material 750.

[0074] A SAP 720 is positioned at the first end of the capsule 700 and within the interior cavity against a platform 715 defined by the second capsule housing portion 711. The platform 715 (i) provides a movement stop for the piston 740, (ii) allows the SAP 720 to exert a force to push the two capsule housing portions 710, 711 apart, and (iii) defines an opening to allow the spring 730 to traverse the length of the interior cavity. In addition, the capsule 700 includes a dissolvable dye 770 positioned within a small cavity at the second end of the capsule 700, which is covered by a second enteric material 780. As discussed with respect to examples shown above, the second enteric material 780 may be a different material than enteric material 750, though in some cases it may be the same. In this example, the enteric material 750 is configured to degrade within the small intestines, while the second enteric material 780 is configured to degrade within the large intestines, exposing the dissolvable dye 770. As discussed above, the dye 770 may allow the capsule to be more easily retrieved from the patient’s stool.

[0075] Figure 7B illustrates the capsule 700 after the SAP has been exposed to a liquid and has begun to expand. After the capsule 700 has been ingested, it may encounter the contents of the patient’s gastrointestinal tract, which may flow through the first set of inlet ports 712 and interact with the SAP, causing it to swell. As can be seen, the SAP’s swelling forces the first capsule housing portion 710 to slide away from the second capsule housing portion 711, opening the second set of inlet ports 714. However, the enteric material 750 and the piston 740 obstruct the interior cavity, preventing the material from entering the interior cavity.

[0076] Once the capsule 700 has moved its way into the patient’s small intestine, the enteric material 750 begins to degrade, and ultimately the piston 740 detaches from the enteric material 750 and the spring 730 retracts the piston 740 through the interior cavity. The movement of the piston 740 generates a low pressure region within the interior cavity, drawing material from the exterior environment into the interior cavity.

[0077] Figure 7C illustrates the example capsule 700 after the piston has traversed the interior cavity and its movement has been halted by the platform 715. The piston’s movement has drawn a sample of intestinal contents 760 into the interior cavity. At this time, the enteric material 750 has degraded and the second set of inlet ports is open.

[0078] Figure 7D illustrates the capsule after the piston has encountered the platform 715 and the spring 730 now pulls the first capsule housing portion 710, causing it to slide with respect to the second capsule portion 711, closing the second set of inlet ports 714 and sealing sampled intestinal contents 760 within the interior cavity. Once the capsule 700 reaches the patient’s large intestines, the second enteric material 780 degrades, exposing the dissolvable dye 770.

[0079] In this example, the capsule 700 is sized to capture at least 200 microliters of material within the interior cavity, however, in some examples, it may be configured to capture 250 or 300 microliters (or more) to help ensure a minimum amount of material, e.g., 200 microliters, is captured. Further, example capsules, such as the capsule 700 shown in Figures 7A-7D, may be constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule may be constructed of such a biodegradable material to allow part or all of the capsule 700 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract. Further, any suitable SAP may be employed, such as those discussed above. [0080] Referring now to Figures 8A-8B, Figures 8A-8B show an example ingestible capsule 800 for sampling intestinal contents. In this example, Figure 8A illustrates the capsule 800 before it has been ingested. The capsule is formed by a capsule housing 810 that defines an interior cavity that contains a partial vacuum. A first end of the capsule is sealed by one-way valve 820, such as a ball- check valve (or any other suitable one-way valve). The first end of the capsule 800 also has an end cap 830 constructed of an enteric material configured to dissolve in a patient’s intestinal tract. A deflated inflatable bladder 840 is positioned within the interior cavity and sealed to the one-way valve 830.

[0081] Figure 8B illustrates the capsule 800 after it has reached the patient’s intestinal tract. Once the enteric material 830 encounters material within the intestinal tract, it begins to degrade and ultimately fails, exposing the one-way valve 820 to the exterior environment. The partial vacuum within the interior cavity then causes the one-way valve, which is no longer experiencing equal pressure on both sides of the valve, to open and the inflatable bladder 840 begins to draw material from the exterior environment through the one way valve 820. Once the bladder 840 has sufficiently expanded, the one-way valve 830 closes, sealing the interior cavity and the captured material 850 within the inflatable bladder 840. The capsule 800 then traverses the remainder of the patient’s intestinal tract and may be retrieved from the stool. While not illustrated in this example, in some examples, the capsule 800 may also have a quantity of a dissolvable dye covered by a second enteric material configured to dissolve within the large intestines, which as discussed above, releases the dye, allowing the capsule 800 to be more easily identified within the patient’s stool.

[0082] In this example, the capsule 800 is sized to capture at least 200 microliters of material within the interior cavity, however, in some examples, it may be configured to capture 250 or 300 microliters (or more) to help ensure a minimum amount of material, e.g., 200 microliters, is captured. Further, example capsules, such as the capsule 800 shown in Figures 8A-8B, may be constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule 800 may be constructed of such a biodegradable material to allow part or all of the capsule 800 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract. [0083] Referring now to Figures 9A-9F, Figures 9A-9F illustrate an example ingestible capsule 900 for sampling intestinal contents. Figure 9A illustrates the capsule 900 before it is ingested. In this example, the capsule 900 has a capsule housing 910 that defines an interior cavity. At a first end of the capsule 900, the capsule housing 910 defines one or more inlet ports 912 that are sealed by a one-way valve 940. In this example, the one-way valve 940 is an umbrella valve, however, any suitable one-way valve may be employed.

[0084] A spring 920 (or other biasing member) is positioned within the interior cavity and compressed between the first end of the capsule 900 and a piston 930. The piston 930 engages with the interior walls of the interior cavity to provide a seal with the interior wall to prevent material from moving past the piston 930. The piston 930 is positioned against an enteric capsule 950, which fills the remainder of the interior cavity and obstructs a second set of inlet ports 914 at the second end of the capsule 900. In this example, the enteric capsule 950 is configured to degrade in a patient’s small intestines, though in some examples, it may be configured to degrade in the patient’s large intestines (or even the patient’s stomach in some examples). Figure 9B provides a cross-sectional view of the example capsule 900, illustrating the arrangement of the interior components of the capsule 900.

[0085] Figures 9C to 9F illustrate the example capsule 900 after it has been ingested and the enteric capsule 950 has begun to degrade. Because the second set of inlet ports 914 is obstructed by the enteric capsule 950, once the capsule 900 reaches the right environment, the enteric capsule 950 will begin to degrade. In Figure 9C, the enteric capsule 950 has begun to degrade and shrink in size. As a result, the spring 920 is able to expand, pressing the piston 930 against the enteric capsule 950 as it degrades. The movement of the piston 930 creates a low pressure region within the interior cavity, which opens the one-way valve 940 and draws material 960 from the exterior environment into the interior cavity.

[0086] As the enteric capsule 950 continues to degrade, as shown in

Figures 9C-9F, the piston 930 is moved through the interior cavity by the spring 920 and material 960 continues to be drawn into the interior cavity. Ultimately, the enteric capsule 950 may entirely dissolve, shown in Figures 9F, and the piston 930 traverses the entire length of the interior cavity. Once the piston’s movement halts and the pressure within the interior cavity equalizes with the exterior environment, the one-way valve 940 closes, sealing the captured material 960 within the interior cavity.

[0087] In this example, the capsule 900 is sized to capture at least 200 microliters of material within the interior cavity, however, in some examples, it may be configured to capture 250 or 300 microliters (or more) to help ensure a minimum amount of material, e.g., 200 microliters, is captured. Further, example capsules, such as the capsule 900 shown in Figures 9A-9F, may be constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule 900 may be constructed of such a biodegradable material to allow part or all of the capsule 900 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract.

[0088] Further, while not illustrated in Figures 9A-9F, in some examples, a dissolvable dye may be included within the capsule 900 and sealed with a second enteric material. As discussed above with respect to other example capsules, the second enteric material may dissolve within the patient’s large intestines, releasing the dye, allowing the capsule 900 to be more easily retrieved from the patient’s stool.

[0089] In some examples, the enteric capsule 950 may instead be another material, such as a FDA-approved polycarbonate or a PVA. In such an example, the end cap of the capsule 900 at the second end of the capsule having the second set of inlet ports 914 may be constructed of an enteric material. When the enteric material dissolves, the capsule 950 may be ejected from the ingestible capsule 900 and the piston 930 may be driven the length of the cavity by the spring 920.

[0090] Referring now to Figures 10A-10B, Figures 10A-10B illustrate an example capsule 1000 for sampling intestinal contents. Figure 10A illustrates the example capsule 1000 before it has been ingested. In this example, the capsule 1000 is constructed of two capsule housing portions 1010, 1011. The first capsule housing portion 1010 encloses the second capsule housing portion 1011 and the two capsule housing portions 1010, 1011 are configured to rotate relative to each other. The second capsule housing 1011 defines an interior cavity of the capsule 1000, which contains a partial vacuum. In addition, each of the two capsule housing portions 1010, 1011 define a respective inlet port 1012, 1014. In the capsule’s initial configuration, the two capsule housing portions 1010, 1011 are oriented so the inlet ports 1012, 1014 align and provide a pathway from the exterior environment into the interior cavity of the capsule 1000.

[0091] The capsule 1000 also includes a biasing member 1030, such as a piece of flexible plastic, and a quantity of enteric material 1040. The biasing member 1030 is coupled to the two capsule housing portions 1010, 1011 and is initially biased to apply a torque to the second capsule housing member 1011.

The enteric material 1040 is also coupled between the two capsule housing portions 1010, 1011 and prevents relative rotation of the two capsule housing portions 1010, 1011, despite the torque applied by the biasing member 1030.

[0092] The entire capsule 1000 is also coated in an enteric material (not shown), which seals the outermost inlet port 1012, preventing material from flowing through the inlet ports 1012, 1014 into the interior cavity and helping maintain the partial vacuum within the interior cavity. In this example, both the enteric coating and the quantity of enteric material 1040 are configured to degrade within a patient’s small intestines, but in some examples they may both be configured to degrade within a patient’s large intestines or even in a patient’s stomach.

[0093] Figure 10B shows the example capsule 1000 after it has obtained a sample from the patient’s intestines or stomach, depending on the selected enteric material. Initially, the enteric coating degrades upon reaching the appropriate environment, e.g., the small intestines. Once the enteric coating degrades, the inlet ports 1012, 1014 expose the interior cavity to the exterior environment. The partial vacuum within interior cavity then draws material into the interior cavity through the inlet ports 1012, 1014. As the material is collected, the quantity of enteric material 1040 is exposed to the material and begins to degrade and ultimately decouples from the first or second capsule housing portion 1010, 1011. Once the quantity of enteric material 1040 decouples from a housing portion 1010, 1011, the torque applied by the biasing member 1030 rotates the two housing portions 1010, 1011 with respect to each other, causing the two inlet ports 1012, 1014 to become mis-aligned, sealing the interior cavity and capturing the sampled material.

[0094] While not illustrated in Figures 10A-10B, in some examples, a dissolvable dye may be included within the capsule 1000 and sealed with a second enteric material. As discussed above with respect to other example capsules, the second enteric material may dissolve within the patient’s large intestines, releasing the dye, allowing the capsule 1000 to be more easily retrieved from the patient’s stool.

[0095] In this example, the capsule 1000 is sized to capture at least 200 microliters of material within the interior cavity, however, in some examples, it may be configured to capture 250 or 300 microliters (or more) to help ensure a minimum amount of material, e.g., 200 microliters, is captured. Further, example capsules, such as the capsule 1000 shown in Figures 10A-10B, may be

constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule 1000 may be constructed of such a biodegradable material to allow part or all of the capsule 1000 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract.

[0096] Referring now to Figures 11A-11B, Figures 11A-11B show an example capsule 1100 for sampling intestinal contents. Figure 11A shows a cross- section of the example capsule 1100 before it has been ingested. The capsule 1100 has a capsule housing 1110 that defines an interior cavity and two inlet ports 1112, 1114 on opposite ends of the capsule housing 1110. In addition, a mesh capsule insert 1140 is positioned within the cavity and two quantities of SAP 1130 positioned at each end of the capsule between the mesh capsule 1140 and the capsule housing 1110. The mesh capsule insert 1140 has multiple openings that may allow material to flow through the mesh, while preventing movement of the SAP 1130 through the openings.

[0097] The entire capsule housing 1110 has an enteric coating 1120 that obstructs the two inlet ports 1112, 1114. In this example, the enteric coating 1120 is configured to degrade within a patient’s small intestines, though in some examples, it may be configured to degrade within the patient’s large intestines, or even within the patient’s stomach. Further, while not shown in this example, in some examples, a dissolvable dye may be included within the capsule 1100 and sealed with a second enteric material. As discussed above with respect to other example capsules, the second enteric material may dissolve within the patient’s large intestines, releasing the dye, allowing the capsule 1100 to be more easily retrieved from the patient’s stool.

[0098] Figures 11B illustrates the example capsule 1100 after it has been ingested and reached an environment in which the enteric coating 1120 degrades. After the enteric coating 1120 degrades, the two inlet ports 1112, 1114 are opened and material from the exterior environment is drawn into the interior cavity by the partial vacuum. As the material flows through the inlet ports 1112, 1114 and through the mesh capsule insert 1140, it encounters the SAP, which begins to swell. Over time the SAPs swell to entirely fill the respective volumes between the mesh capsule insert 1140 and the capsule housing 1110, which obstructs the inlet ports 1112, 1114, sealing the interior cavity and the captured sample 1150. The capsule 1100 may then traverse the remainder of the patient’s intestinal tract and be retrieved from the patient’s stool.

[0099] In this example, the capsule 1100 is sized to capture at least 200 microliters of material within the interior cavity, however, in some examples, it may be configured to capture 250 or 300 microliters (or more) to help ensure a minimum amount of material, e.g., 200 microliters, is captured. Further, example capsules, such as the capsule 1100 shown in Figures 11A-11B, may be

constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule 1100 may be constructed of such a biodegradable material to allow part or all of the capsule 1100 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract.

[00100] Referring now to Figures 12A-12B, Figures 12A-12B show an example ingestible capsule 1200 for sampling intestinal contents. Figure 12A illustrates the example capsule 1200 before it has been ingested. In this example, the capsule 1200 has a perforated capsule housing 1210 that has two end caps 1240, 1242 (shown in Figure 12B), defines an interior cavity, and is encapsulated within an enteric coating 1220. The capsule 1200 contains a partial vacuum, which is maintained by the enteric coating. A gelling agent 1230, such as a gelatin powder is contained within the interior cavity of the capsule 1200.

Further, while not shown in this example, in some examples, a dissolvable dye may be included within the capsule 1200, such as within one of the end caps 1240, 1242 of the capsule housing 1200, and sealed with a second enteric material. As discussed above with respect to other example capsules, the second enteric material may dissolve within the patient’s large intestines, releasing the dye, allowing the capsule 1200 to be more easily retrieved from the patient’s stool.

[00101] Figure 12B shows the example capsule 1200 after it has captured a sample. Once the capsule 1200 reaches environment that degrades the enteric coating 1220, one or more perforations become exposed to the exterior

environment, and the partial vacuum within the capsule draws material into the interior cavity. The sampled material then interacts with the gelling agent 1230, and begins to gel. Ultimately, as can be seen, the enteric coating 1220 degrades and the interior cavity fills (at least partially) with a gellated sample 1250 of material. The capsule 1200 may then traverse the remainder of the patient’s intestinal tract and be retrieved from the patient’s stool.

[00102] In this example, the capsule 1200 is sized to capture at least 200 microliters of material within the interior cavity, however, in some examples, it may be configured to capture 250 or 300 microliters (or more) to help ensure a minimum amount of material, e.g., 200 microliters, is captured. Further, example capsules, such as the capsule 1200 shown in Figures 12A-12B, may be

constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule 1200 may be constructed of such a biodegradable material to allow part or all of the capsule 1200 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract.

[00103] Referring now to Figures 13A-13C, Figures 13A-13C show an example ingestible capsule 1300 for sampling intestinal contents. The

configuration shown in Figure 13A is prior to the capsule 1300 being ingested. In this example, the capsule 1300 has a capsule housing 1310 the defines an interior cavity. At a first end of the capsule 1300, the capsule housing 1310 defines one or more inlet ports 1312 that are sealed by a one-way valve 1340. In this example, the one-way valve 1340 is an umbrella valve, however, any suitable one-way valve may be employed.

[00104] A spring 1320 (or other biasing member) is positioned within the interior cavity and compressed between the first end of the capsule 1300 and a piston 1330. The piston 1330 engages with the interior walls of the interior cavity to provide a seal with the interior wall to prevent material from moving past the piston 1330. The piston 1330 is positioned against an electronic triggering capsule 1350, which fills the remainder of the interior cavity and obstructs a second set of inlet ports 1314 at the second end of the capsule 1300. The electronic triggering capsule 1350 is described in more detail with respect to Figures 13B; however, generally, the electronic triggering capsule 1350 senses a pH of a material within an exterior environment. Once the pH reaches a predetermined value, the electronic triggering capsule 1350 triggers itself to be ejected from the ingestible capsule 1300.

[00105] Figure 13B illustrates the electronic triggering capsule 1350 from Figure 13A. The electronic triggering capsule 1350 has a housing 1351 that encloses a battery 1352, a microprocessor 1353, a pH sensor 1354, an

electronically activated latch 1355, and a liquid activated switch 1356. Before the capsule 1300 of Figure 13A is ingested, the electronics within the electronic triggering capsule 1350 are disabled. However, once liquid contacts the liquid activated switch 1356, e.g., after the capsule is ingested or by wetting the capsule prior to ingestion, the electronics 1353-1355 are enabled. For example, the battery 1352 may be switched into electrical communication with the other electronic components, or a reset line on the microprocessor 1353 or a clock (not shown) may be disabled.

[00106] In this example, the liquid activated switch comprises two electrical contacts wherein a conductive liquid, e.g., liquid within a patient’s gastrointestinal tract, may provide a conductive path between the two contacts, closing a circuit and thereby enabling the electronic triggering capsule 1350. Further, liquid may contact the pH sensor 1354, which may monitor a pH level within the liquid and transmit one or more signals to the microprocessor 1353 indicating the sensed pH.

[00107] When the microprocessor 1353 determines that a sensed pH meets or exceeds a predetermined threshold (once, or for a predetermined period of time), it may disable or close the electronically activated latch 1355. Closing the electronically activated latch 1355 may decouple the electronic triggering capsule 1350 from the capsule housing 1310. The force applied by the spring 1320 to the piston 1330 and the electronically triggering capsule 1350 may then eject the electronically triggering capsule 1350 from the ingestible capsule 1300. The piston 1330 may then be forced across the interior cavity, thereby pulling exterior material through the one-way valve 1340 and into the ingestible capsule.

[00108] Figure 13C illustrates the ingestible capsule 1300 and the electronic triggering capsule 1350 after it has been ejected. As is shown, the piston 1330 has been forced across the interior cavity and material has been drawn into the cavity via the one-way valve 1340. The ingestible capsule 1300 and the electronic triggering capsule 1350 may then be retrieved from the patient’s stool at a later time. [00109] In this example, the capsule 1300 is sized to capture at least 200 microliters of material within the interior cavity, however, in some examples, it may be configured to capture 250 or 300 microliters (or more) to help ensure a minimum amount of material, e.g., 200 microliters, is captured. Further, example capsules, such as the capsule 1300 shown in Figures 13A-13B, may be

constructed of any suitable material, including an FDA-approved polycarbonate material, or a biodegradable material, such as PVA. Further, some or all components of the capsule 1300 may be constructed of such a biodegradable material to allow part or all of the capsule 1300 to dissolve within the patient’s body should it become lodged within the patient’s gastro-intestinal tract.

[00110] While not illustrated in Figures 13A-13C, in some examples, a dissolvable dye may be included within the capsule 1300 and sealed with a second enteric material. As discussed above with respect to other example capsules, the second enteric material may dissolve within the patient’s large intestines, releasing the dye, allowing the capsule 1300 to be more easily retrieved from the patient’s stool.

[00111] In this example, the microprocessor 1353 may be a microprocessor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), field programmable gate arrays (FPGAs), and state machines. Such processors may further comprise programmable electronic devices such as PLCs,

programmable interrupt controllers (PICs), programmable logic devices (PLDs), programmable read-only memories (PROMs), electronically programmable read only memories (EPROMs or EEPROMs), or other similar devices.

[00112] Further, the microprocessor 1353 may comprise, or may be in communication with, media, for example computer-readable storage media, that may store instructions that, when executed by the processor, can cause the processor to perform the steps described herein as carried out, or assisted, by a processor. Examples of computer-readable media may include, but are not limited to, an electronic, optical, magnetic, or other storage device capable of providing a processor, such as the processor in a web server, with computer- readable instructions. Other examples of media comprise, but are not limited to, a floppy disk, CD-ROM, magnetic disk, memory chip, ROM, RAM, ASIC, configured processor, all optical media, all magnetic tape or other magnetic media, or any other medium from which a computer processor can read. The processor, and the processing, described may be in one or more structures, and may be dispersed through one or more structures.

[00113] The foregoing description of some examples has been presented only for the purpose of illustration and description and is not intended to be exhaustive or to limit the disclosure to the precise forms disclosed. Numerous modifications and adaptations thereof will be apparent to those skilled in the art without departing from the spirit and scope of the disclosure.

[00114] Reference herein to an example or implementation means that a particular feature, structure, operation, or other characteristic described in connection with the example may be included in at least one implementation of the disclosure. The disclosure is not restricted to the particular examples or implementations described as such. The appearance of the phrases“in one example,”“in an example,”“in one implementation,” or“in an implementation,” or variations of the same in various places in the specification does not necessarily refer to the same example or implementation. Any particular feature, structure, operation, or other characteristic described in this

specification in relation to one example or implementation may be combined with other features, structures, operations, or other characteristics described in respect of any other example or implementation.

[00115] Use herein of the word“or” is intended to cover inclusive and exclusive OR conditions. In other words, A or B or C includes any or all of the following alternative combinations as appropriate for a particular usage: A alone; B alone; C alone; A and B only; A and C only; B and C only; and A and B and C.