Systems, methods and devices for epithelial, mucosal and gastrointestinal sampling

Abstract

An exemplary pill can be provided for sampling biological compounds from various epithelial or mucosal linings. The exemplary pill can include a mesh of pores on the surface of the pill. The pill can also include an internal sampling canty connected to the mesh of pores. The exemplary pill can be configured to be ingested, travel through the gastrointestinal tract (GIT), scrape the surface, causing transfer of microbes to the mesh of pores and then to the sampling cavitiy. The exemplary pill can also include a magnet or other materials or techniques to assist with retrieval upon egestion.

Description

SYSTEMS, METHODS AND DEVICES FOR EPITHELIAL, MUCOSAL AND GASTROINTESTINAL SAMPLINGCROSS REFERENCE TO RELATED APPLICATION(S)

[0001] This application relates to U.S. Provisional Patent Application Serial No. 63 / 554,507, filed on February 16, 2024, the entire disclosure of which is incorporated herein by referenceFIELD OF THE DISCLOSURE

[0002] The present disclosure relates to microbial sampling and more particularly to systems, methods and ingestible devices for sampling of the epithelial and / or mucosal linings of the body such as the gastrointestinal ((GI) tract - “GIT”), oral cavity, respiratory, urogenital tracts and skin.BACKGROUND INFORMATION

[0003] Studies have shown that the human body consists of trillions of microbes, most of them concentrated in the gut. These microbial communities have been shown to play a significant role in various immune & inflammatory diseases, pregnancy, early brain development in babies and even in regulation of human emotions. In order to fully understand the role of these gastrointestinal microbial communities, it is crucial to access and sample them. Existing techniques for investigating and sampling these microbes include stool sampling, endoscopy, postmortem histology and ingestible pills. These techniques have limitations such as, e.g., in endoscopy which is an in-patient procedure and requires several hours and skilled persons thereby making it difficult to perform in a routine manner.

[0004] Ingestible pills have been demonstrated to sample bacteria. However, due to their complexity in design, sampling and operation they have not been widely used. Thus, the current standard for gastrointestinal sampling remains stool sampling which does not provide an accurate representation of the various microbial communities residing in the gut. In addition to sampling inaccuracy, large areas of the gut such as the small intestine are inaccessible for direct sampling using existing techniques. The small intestine (SI) is particularly important as it harbors a significant community of microbes that have been linked to several diseases ranging from metabolic, neurological, inflammatory and immune disorders

[0005] Thus, there is a need to address and / or improve at least these deficiencies which exist in the previous systems and methods by providing systems, methods and ingestibledevices that can sample the gut microbiome, e.g., with a high accuracy and without causing any notable damage to the GIT and / or necessitating an invasive procedure.SUMMARY OF EXEMPLARY EMBODIMENTS

[0006] The following is intended to be a brief summary of the exemplary embodiments of the present disclosure, and is not intended to limit the scope of the exemplary embodiments

[0007] To that end, according to certain exemplary embodiments of the present disclosure, methods and systems can be provided for sampling microbial colonies in the gastrointestinal tract. For example, it is possible to load a mesh pill inside a capsule, cause and or direct the loaded mesh pill to be ingested, retrieve the mesh pill upon egestion, and retrieve the microbial colonies sampled from the mesh pill

[0008] For example, the gelatin, HPMC, or similar capsule can have a low pH resistant coating. In addition, or alternatively, the capsule can be dissolved in the higher pH environment of the small intestines. In addition or alternatively, the mesh pill can sample or scrape one or more surfaces of the small intestines. The scraping can cause microbes to transfer from the one or more surfaces to one or more pores in the mesh pill. Additionally, or alternatively, the microbes in the one or more pores in the mesh pill can be forced into a sampling volume and or a subsequent porous mesh or meshes by pressure exerted from the gastrointestinal tract.

[0009] According to additional exemplary embodiments of the present disclosure, a pill can be provided for sampling microbial colonies in the small intestine. Such exemplary pill can comprise a mesh of pores on the surface of the pill and an internal sampling cavity connected to the mesh of pores. The internal sampling cavity can comprise a second mesh of pores disposed within the pill. Each mesh structure can have varying geometric topologies

[0010] The samples collected by the pill can be or include microorganisms comprising bacteria, viruses, fimgi, analytes, etc. The mesh of pores can comprise a unique architecture or topology to allow efficient sampling. In addition, or alternatively, the mesh of pores can comprise one or more geometric elements. The one or more geometric elements can comprise multiple porous entities with similar or different porous arrangements, differing porosity, pore shape, pore size, pore tortuosity, pore length, pore distribution, surface area. The dimensions of the mesh of pores and internal sampling cavity can be modified based on a sampling target and location. The internal sampling cavity or mesh of pores can be modified by one or more chemical or physical treatments or processes such as surface modification,modifying charge, phobicity and phillicity, chemoattractants, bacteriophilic solutions, absorbents, analytes and preserving media to allow sampling or sample preservation.[OOH] In some exemplary embodiments of the present disclosure, exemplary systems, methods, and devices can be provided which can sample at least one biological compound, bio-active chemical compound, virus, or microorganism in an epithelial lining or a mucosal lining by applying a mesh structure to an epithelial or mucosal surface, retrieving the mesh structure subsequent to applying to the epithelial surface, and retrieving the at least one biological compound sampling from the mesh structure. The exemplary mesh structure can be at least partially contained by a secondary container. In some exemplary embodiments, the epithelial lining can be the gastrointestinal tract, the urogenital tract, the respiratory tract, the auditory canal, the oral cavity, the skin, etc. The secondary container can include a pH resistant coating which can be configured to dissolve in a higher or lower pH environment of the small intestine or a large intestine, respectively.

[0012] In some exemplary embodiments of the present disclosure, the epithelial surface can comprise one or more surfaces of the small intestines and the mesh structure can be configured to sample or scrape one or more surfaces of the small intestines after being ingested. The scraping can cause a portion of at least one biological compound to transfer from the one or more surfaces to one or more pores in the mesh structure, and the portion of the at least one biological compound in the one or more pores in the mesh structure can be forced into a sampling cavity by pressure exerted from the intestine.

[0013] According to further exemplary embodiments of the present disclosure, exemplary systems, methods, and devices can be provided which can sample at least one microbial colony in an intestine, comprising a mesh pill configured and structured to (i) be loaded inside a capsule, (ii) be ingested to reach the intestine, (iii) scrape one or more area or surfaces of the intestine, (iv) be retrieved upon egestion, and (v) a lattice structure mathematically configured to retrieve the microbial colonies samples from the mesh pill.

[0014] These and other objects, features and advantages of the exemplary embodiments of the present disclosure will become apparent upon reading the following detailed description of the exemplary embodiments of the present disclosure, when taken in conjunction with the appended claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Further objects, features and advantages of the present disclosure will become apparent from the following detailed description taken in conjunction with the accompanying Figures showing illustrative embodiments of the present disclosure, in which:

[0016] Figure 1(a) is an exemplary computer-aided design (CAD) drawing of a mesh pill showing the outer and inner cross-sectional design according to an exemplary embodiment of the present disclosure;

[0017] Figure 1(b) is an exemplary three-dimensional view of the printed mesh pill according to an exemplary embodiment of the present disclosure;

[0018] Figure 1 (c) is an illustration of the magnet with the magnetic properties provided inside the exemplary printed mesh pill of Fig. 1(b) to assist in a retrieval according to an exemplary embodiment of the present disclosure;

[0019] Figure 2(a) is an exemplary scanning electron microscopy (SEM) image of the mesh pill according to an exemplary embodiment of the present disclosure;

[0020] Figure 2(b) is the exemplary SEM image of a single port of the mesh pill according to an exemplary embodiment of the present disclosure;

[0021] Figure 3(a) is an exemplary illustration of a mesh pill encapsulated in a pH sensitive capsule according to an exemplary embodiment of the present disclosure;

[0022] Figure 3(b) is an exemplary illustration of sampling in the intestine with a mesh pill according to an exemplary embodiment of the present disclosure;

[0023] Figure 3(c) is an exemplary illustration of a microbiome sampling process according to an exemplary embodiment of the present disclosure;

[0024] Figures 4(a) and 4(c) are exemplary computed tomography (CT) scan images showing two types of exemplary mesh pills - one with a smaller sampling cavity in Figure 4(a), and one with a smaller mesh wall with pores, although with a larger sampling cavity in Figure 4(b), according to an exemplary embodiment of the present disclosure;

[0025] Figure 5(a) is an exemplary SEM image of the front of the mesh pill placed on a section of the small intestine according to an exemplary embodiment of the present disclosure;

[0026] Figure 5(b) is an exemplary SEM image of the side of the mesh pill of Figure 5(a) placed on a section of the small intestine according to another exemplary embodiment of the present disclosure;

[0027] Figure 5(c) is an exemplary SEM image of a small intestinal villi according to an exemplary embodiment of the present disclosure;

[0028] Figure 6(a) is an exemplary SEM image of the mesh pill that was passed through the small intestines of a rat according to an exemplary embodiment of the present disclosure;

[0029] Figure 6(b) is an exemplary SEM image of an outer area of the mesh pill of Figure 6(a) passed through the small intestines of a rat showing bacteria on the outside according to an exemplary embodiment of the present disclosure;

[0030] Figure 6(c) is an exemplary magnified image of a pore showing bacteria (rod-like structures) inside according to an exemplary embodiment of the present disclosure;

[0031] Figure 7 is an exemplary bar chart illustrating the types and amounts of bacteria in samples collected using four different methods where Pill. SI is sample collected from pill after passing through small intestine ex vivo. Hom. SI is the ex vivo sample of tissue homogenized. Fec.Fr are feces obtained from within ex vivo gut. Fec.Sol feces collected after excretion from animal according to an exemplary embodiment of the present disclosure;

[0032] Figure 8 is an exemplary bar chart illustrating in vivo data for relative abundance of bacterial phyla in samples collected from (a) intestine, (b) colon, (c) feces, and (d) the mesh structure according to an exemplary embodiment of the present disclosure;|0033| Figure 9(a) is an exemplary computer-aided design (CAD) drawing showing collapsed, exploded, and cross-sectional views of a complex mesh structure design according to an exemplary embodiment of the present disclosure;

[0034] Figure 9(b) is an image of the complex mesh structure of Figure 9(a) according to an exemplary embodiment of the present disclosure;

[0035] Figure 9(c) is an exemplary CT image the complex mesh structure of Figure 9(a) according to an exemplary embodiment of the present disclosure; and

[0036] Figure 10 is an exemplary mesh structure for epithelial sampling from non-GI surfaces according to an exemplary embodiment of the present disclosure.

[0037] Throughout the drawings, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments. Moreover, while the present disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments and is not limited by the certain exemplary embodiments illustrated in the figures and the appended claims.DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0038] The following description of exemplary embodiments provides non-limiting representative examples referencing numerals to particularly describe features and teachings of different aspects of the present disclosure. The exemplary embodiments described should be recognized as capable of implementation separately, or in combination, with other exemplary embodiments from the description of the exemplary embodiments. A person of ordinary skill in the art reviewing the description of the exemplary embodiments should be able to learn and understand the different described aspects of the present disclosure. The description of the exemplary embodiments should facilitate understanding of the invention to such an extent that other implementations, not specifically covered but within the knowledge of a person of skill in the art having read the description of embodiments, would be understood to be consistent with an application of the exemplary embodiments of the present disclosure.

[0039] The microbiome community of the GIT is believed to influence a wide variety of chronic diseases including neurologic, metabolic, endocrine, immune, inflammatory and digestive disorders. Exemplary systems, methods, and devices according to various exemplary embodiments of the present disclosure can passively sample the intestine thereby giving access to information regarding the microbial communities residing therein. Exemplary systems, methods, and devices according to various exemplary embodiments of the present disclosure can include and / or utilize a capsule with a unique porous mesh architecture developed using a mathematical model. Mesh pills according to exemplary embodiments of the present disclosure can be configured or made capable to sample the gut microbiome from areas of the GIT inaccessible using endoscopic means, particularly the small intestine, with high accuracy. The exemplary design, biologically inert, and disposable nature of the capsule according to exemplary embodiments allow for its mass application in medical settings. Systems, methods, and the device according to the exemplary embodiments of the present disclosure can be readily expanded to sample analytes and luminal contents of the GI tract other than microbiome. In some exemplary embodiments, the exemplary device can be used to delivery therapeutics, including pharmacologic agents, prebiotics, or probiotics for microbiome modulation.

[0040] According to various exemplary embodiments of the present disclosure, the exemplary device can be an entirely passive device for microbiome sampling. The exemplary device can have no moving or changing elements and can include one element that may bereadily fabricated using 3D-printing. For example, figure 1(a) shows an exemplary CAD drawing of an exemplary embodiment of a mesh pill showing the outer 100 and inner cross- sectional design 110. Through careful design of the lattice wall structure, exemplary embodiments of the present disclosure can ensure that (1) GI mucosa is abrasively brushed to collect luminal as well as mucosal-adherent microbes, and / or (2) samples are collected and retained with no need for moving parts or passively expanding / degrading elements. The exemplary device of the present disclosure can collect microbial samples from inaccessible portions of the GIT, which can be far more reflective of the native microbiome than are fecal samples. It should be noted that an exemplary device of the present disclosure can be applied to any epithelial or mucosal lining to sample any biological compound. Figure 1(b) shows an exemplary 3D printed mesh pill 120 and Figure 1(c) shows the exemplary 3D printed mesh pill 120 can be magnetic for ease of retrieval. Figures 4(a) and 4(b) show CT scan images of two exemplary deigns of devices according to exemplary embodiments of the present disclosure. Figure 4(a) shows a mesh structure 410 (e.g., a mesh pill) having mesh pores 415, with a relatively smaller sampling cavity 420. Figure 4(b) shows a mesh structure 430 having mesh pores 435, with a relatively larger internal sampling cavity 440. Figure 10 shows exemplary designs according to exemplary embodiments of the present disclosure for epithelial sampling from non-Gl surfaces.

[0041] According to further exemplary embodiments of the present disclosure, a capsule e.g., that can be referred to as mesh pill, can be provided that can perform microbial sampling of the small intestine with high levels of accuracy. The exemplary mesh pill according to the exemplary embodiments of the present disclosure can be broadly divided into two parts- outer pores and inner area / volume, whereas the outer pores can open into the inner volume. The inner volume can include additional porous elements with differing pore parameters. Figure 2(a) shows an exemplary Scanning Electron Microscopy (SEM) image of a mesh pill and its outer pores 210 according to exemplary systems, methods and digestible devices of exemplary embodiments of the present disclosure. Figure 2(b) shows a magnified image of one of the pores 210 in the exemplary mesh pill of Figure 2(a). The outer core, according to exemplary embodiments of the present disclosure, can include a unique mesh pore structure that can be tailored in shape, size and tortuosity in order to achieve maximal bacterial sampling. For example, every pore can be designed in such a way so as to open into more than one pore and the second pore opens again into multiple pores and so on. This can ensure a maze-like yet symmetrical porous structure that facilitates bacteria to be ushered into theinner area by an intestinal pressure, while preventing their release thereafter. In exemplary embodiments, the design of this interconnected network of pores is realized mathematically. In one exemplary embodiment, the geometry can be designed following spinodal decomposition or a minimal surface. In various exemplary embodiments, the shape, tortuosity and dimensions of the inner cavity may be modified based on the necessary sampling volumes. In another embodiment, the mesh parameters of the inner cavity can be modified based on the targeted sampling area of the GIT. Figures 4(a) and 4(b) show exemplary Computed Tomography (CT) scan images of two different mesh pill embodiments with different sized inner cavities for different sampling sizes. In yet additional exemplary embodiments of the present disclosure, a small magnet can be placed inside the pill to facilitate retrieval from stool.

[0042] With the systems and methods according to the exemplary embodiments of the present disclosure, sampling can be achieved using, e.g., the mesh pill which can be loaded inside a capsule coated with a pH-sensitive coating. Figure 3(a) shows an exemplary illustration of a mesh pill 310 encapsulated in a pH sensitive capsule 320 according to exemplary systems, methods and ingestible devices of exemplary embodiments of the present disclosure. This coating on capsule 320 can prevent capsule degradation in a low pH environment of the stomach (acidic), and can then disintegrate in the higher pH (basic environment) of the small intestine, thereby releasing the mesh pill 310. The mesh pill 310 can then traverse through the intestine sampling the microbial colonies present there. Figure 3(b) shows an exemplary illustration of a mesh pill 310 passing through a section of the intestine 325 depicting bacterial sampling 330 from the intestine. Figures 5(a) and 5(b) show exemplary Scanning Electron Microscopy (SEM) images of a mesh pill 510 placed on top of villi 520 on a section of the small intestine, and Figure 5(c) shows an SEM image of villi 520 within a section of the small intestine. The pill can be excreted and collected using a magnet. The contents of the pill can then be analyzed to identify the sampled bacteria.

[0043] Figure 3(c) shows an illustration of the exemplary microbiome sampling process according to an exemplary embodiment of the present disclosure. For example, at step 340, the mesh structure (e.g., pill) encased in a coated capsule can be ingested. Then, at step 350, the capsule can disintegrate within the small intestines. At step 360, the exposed mesh structure can move through the intestines, scraping the intestinal lining, thereby collecting a biological compound sample. At step 370, the mesh structure (e.g., mesh pill) including the collected sample(s) can be egested. At step 380, the mesh structure can be collected. Theegested mesh pill can be retrieved from the fecal matter using a magnet. At step 390, the bacterial DNA within the pill can be extracted and analyzed according to exemplary systems, methods and ingestible devices of exemplary embodiments of the present disclosure. Figures 6(a)-(c) show exemplary SEM images of a mesh pill, according to exemplary systems, methods and ingestible devices of exemplary embodiments of the present disclosure that was passed through the small intestine of a rat. For example, Figure 6(a) shows a full view of a mesh structure 600 that was passed through the intestine of a rat. Figure 6(b) shows an outer area of mesh structure 600 with bacteria 610 on the outside. Figure 6(c) shows a magnified image of a pore showing bacteria (rod-like structures) within the pore.

[0044] The systems and methods according to the exemplary embodiments of the present disclosure can include multiple mesh structures embedded within each other. For example, Figure 9(a) shows a CAD drawing of a complex mesh structure 900 comprising one mesh structure 910 embedded within another mesh structure 920. Figure 9(b) is an image of the exemplary complex mesh structure, and Figure 9(c) is a CT image of the same, showing both mesh structures, 910 and 920.

[0045] According to exemplary embodiments of the present disclosure, the disclosed pill demonstrates a higher sampling accuracy compared to fecal samples, which is the current standard sampling technique. According to exemplary embodiments of the present disclosure, there is a high degree of similarity between pill samples and a homogenized section of the small intestine. For example, Figure 7 shows an exemplary Stacked bar plot of most abundant bacteria phyla in 4 types of samples. In Figure 7, Pill. SI is shown as a sample collected from pill after passing through small intestine ex vivo, Hom. SI is the ex vivo sample of tissue homogenized, Fec.Fr are feces obtained from within ex vivo gut, and Fee. Sol feces are collected after excretion from animal. This confirms the effectiveness of the sampling methods, systems, and device of exemplary embodiments of the present disclosure.

[0046] Furthermore, Figure 8 shows an exemplary bar chart illustrating in vivo data for the types and amounts of bacterial phyla in samples collected from (a) small intestine, (b) colon, (c) feces, and (d) the mesh structure *e.g., a mesh pill) according to an exemplary embodiment of the present disclosure. For example, such exemplary bar chart includes in vivo data from an ingestible embodiment of the present disclosure, and thus Figure 8 shows that exemplary embodiments of the present disclosure can successfully sample from the small intestine.EXEMPLARY MARKET COMMERCIALIZATION

[0047] The majority of diseases known to occur in humans have been associated with some microbial component. Several metabolic, immune, inflammatory, neurological and gastrointestinal disorders have been linked to an imbalance in the GI microbial community. The most prevalent technique to identify the microbes residing in the GIT is by stool testing. It is recognized, however, that stool does not adequately represent the breadth of microbiome diversity in the GI tract. However, no simple or viable alternative is known to exist, and thus, stool sampling remains the standard used in clinical trials and practice for diagnosis and treatment. An effective means to easily sample the microbial populations not present in stool, such as that offered by exemplary embodiments of the present disclosure, significantly (1) enhances understanding of disease, and (2) improves diagnosis and therapy.

[0048] The ease of administration and retrieval of the pill, by magnet or otherwise, according to exemplary embodiments, as well as flexibility in modifying pill parameters will extend its usage to humans and animals in both clinical and research settings.

[0049] According to exemplary embodiments of the present disclosure, numerous specific details have been set forth. It is to be understood, however, that implementations of the disclosed technology can be practiced without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description. References to “some examples,” “other examples,” “one example,” “an example,” “various examples,” “one embodiment,” “an embodiment,” “some embodiments,” “example embodiment,” “various embodiments,” “one implementation,” “an implementation,” “example implementation,” “various implementations,” “some implementations,” etc., indicate that the implementation(s) of the disclosed technology so described may include a particular feature, structure, or characteristic, but not every implementation necessarily includes the particular feature, structure, or characteristic. Further, repeated use of the phrases “in one example,” “in one exemplary embodiment,” or “in one implementation” does not necessarily refer to the same example, exemplary embodiment, or implementation, although it may.

[0050] As used herein, unless otherwise specified the use of the ordinal adjectives “first,” “second,” “third,” etc., to describe a common object, merely indicate that different instances of like objects are being referred to, and are not intended to imply that the objects so described must be in a given sequence, either temporally, spatially, in ranking, or in any other manner.

[0051] While certain implementations of the disclosed technology have been described in connection with what is presently considered to be the most practical and various implementations, it is to be understood that the disclosed technology is not to be limited to the disclosed implementations, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

[0052] The foregoing merely illustrates the principles of the disclosure. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements, and procedures which, although not explicitly shown or described herein, embody the principles of the disclosure and can be thus within the spirit and scope of the disclosure. Various different exemplary embodiments can be used together with one another, as well as interchangeably therewith, as should be understood by those having ordinary skill in the art. In addition, certain terms used in the present disclosure, including the specification and drawings, can be used synonymously in certain instances, including, but not limited to, for example, data and information. It should be understood that, while these words, and / or other words that can be synonymous to one another, can be used synonymously herein, that there can be instances when such words can be intended to not be used synonymously. Further, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it is explicitly incorporated herein in its entirety. All publications referenced are incorporated herein by reference in their entireties.

[0053] Throughout the disclosure, the following terms take at least the meanings explicitly associated herein, unless the context clearly dictates otherwise. The term "or" is intended to mean an inclusive “or.” Further, the terms “a,” “an,” and “the” are intended to mean one or more unless specified otherwise or clear from the context to be directed to a singular form.

[0054] This w ritten description uses examples to disclose certain implementations of the disclosed technology, including the best mode, and also to enable any person skilled in the art to practice certain implementations of the disclosed technology, including making and using any devices or systems and performing any incorporated methods.

Claims

WHAT IS CLAIMED IS:

1. A method for sampling at least one biological compound, bio-active chemical compound, virus, or microorganism in an epithelial lining or a mucosal lining, comprising: applying a mesh structure to an epithelial surface, retrieving the mesh structure subsequent to the application thereof to the epithelial surface; and retrieving a sampling of the at one least biological compound from the mesh structure.

2. The method of claim 1, wherein the mesh structure is at least partially enveloped by a secondary' container.

3. The method of claim 1, wherein the epithelial lining is at least a part of the gastrointestinal tract.

4. The method of claim 1, wherein the epithelial lining is at least a part of the urogenital tract.

5. The method of claim 1, wherein the epithelial lining is at least a part of the respiratory tract,6. The method of claim 1, wherein the epithelial lining is at least a part of the auditory canal.

7. The method of claim 1, wherein the epithelial lining is at least a part of the oral cavity7.

8. The method of claim 1, wherein the epithelial lining is at least a part of a skin tissue.

9. The method of claim 2, wherein the secondary^ container has a pH-resistant coating.

10. The method of claim 9, wherein the secondary container dissolves in a higher pH environment or a lower pH environment of a small intestine or a large intestine, respectively.

11. The method of claim 2, wherein the epithelial surface comprises one or more surfaces of the small intestine, and wherein the mesh structure is configured to scrape the one or more surfaces of the small intestine after being ingested.

12. The method of claim 11, wherein the scraping causes at least one portion of the at least one biological compound to transfer from the one or more surfaces to one or more pores in the mesh structure.

13. The method of claim 12, wherein the at least one portion of the at least one biological compound provided in the one or more pores in the mesh structure is forced into a sampling cavity by one of a pressure exerted externally or pressure exerted by a biological surface.

14. The method of claim 1, wherein at sampling of the at one least biological compound collected by the mesh structure are microorganisms which comprise at least one of bacteria, viruses or fungi.

15. A pill for sampling at least one microbial colony in a gastro-intestinal tract, comprising: a mesh of pores provided on a surface of the pill; and an internal sampling cavity connected to the mesh of pores.

16. The pill of claim 15. wherein the internal sampling cavity comprises a second mesh of pores disposed within the pill.

17. The pill of claim 15, wherein at least one sample in the at least one microbial colony collected by the pill are microorganisms which comprise at least one of bacteria, viruses or fungi.

18. The pill of claim 17, wherein the at least one sample in the at least one microbial colony collected by the pill are analytes.

19. The pill of claim 15. wherein the mesh of pores comprises a specific architecture or a topology facilitating an efficient sampling.

20. The pill of claim 15, wherein the mesh of pores comprises one or more geometric elements.

21. The pill of claim 16. wherein each of the mesh structures has a geometric topology’ that is different from one another.

22. The pill of claim 20, wherein the one or more geometric elements comprise at least one of a porosity, a pore size, a tortuosity', a pore distribution, pore length or a surface area.

23. The pill of claim 15, wherein dimensions of (a) the mesh of pores and (b) the internal sampling cavity’ are modifiable based on a sampling target, a sampling volume and a location.

24. The pill of claim 15. wherein the internal sampling cavity’ is modified by one or more bacteriophilic solutions, absorbents, analytes, or preserving material to facilitate a specific sampling.

25. A system for sampling at least one microbial colony in an intestine, comprising: a mesh pill configured and structured to:• be loaded inside a capsule,• be ingested to reach the intestine,• scrape one or more surfaces of the intestine, and• be retrieved upon egestion; and a lattice structure mathematically configured to retrieve samples of the at least one microbial colony from the mesh pill.

26. A system for sampling at least one microbial colony in an epithelial or mucosal lining comprising: a mesh structure configured and structured to:• be ingested to reach an internal area;• scrape one or more surfaces of the internal area;• be retrieved upon removal; and a lattice structure mathematically configured to retrieve the microbial colonies samples from the mesh structure.

27. A system for sampling at least one microbial colony in a gastrointestinal tract (GIT) comprising: a mesh pill configured to scrape an epithelial lining.

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