Patent Application
20190328373
The present invention generally relates to a catheter-shaped sampling device capable of discontinuously and/or continuously sampling the content in a biological conduit, and a method thereof, The conduit may be a biological conduit such as human or animal intestinal tract or gut, but it may also be an industrial conduit. Embodiments of this invention can advance the fields of intestinal endocrinology, endoscopy, and microbiology by extending the sampling device into sections of the intestinal tract and obtaining biochemical and microbe samples in conjunction with a sample gathering and handling system, data acquisition, and data analysis. Although the invention will be illustrated, explained and exemplified with a sampling device for the intestinal tract, it should be appreciated that the present invention can serve clinical diagnostic, treatment and research purposes in other fields, for example, biological conduit including gastrointestinal tract, respiratory tract, and the like.
Many times, the content in a biological conduit needs to be sampled and analyzed. Take human or animal intestinal tract or gut as an example. Small intestine (AKA small bowel) is the part of the gastrointestinal tract between the stomach and the large intestine. The average length of the small intestine in a living person is about 6 meters. The small intestine does not only digest food and absorb nutrients and minerals, but also support the body's immune system. Jejunum is the midsection of the small intestine, connecting the duodenum to the ileum. It is about 2.5 m long, and contains the plicae circulares, and villi that increase its surface area. In the jejunum, digestion products such as sugars, amino acids, and fatty acids are absorbed into the bloodstream. The ileum is the final section of the small intestine, and is about 3 m long. The ileum absorbs mainly vitamin B12 and bile acids, as well as any other remaining nutrients. The ileum joins to the cecum of the large intestine at the ileocecal junction. Peyer's patches located within the ileum are an important part of the digestive tract's local immune system. These patches are part of the lymphatic system, and provide a site for antigens from potentially harmful bacteria or other microorganisms in the digestive tract to be sampled, and subsequently presented to the immune system The jejunum and ileum are suspended in the abdominal cavity by mesentery. The mesentery is part of the peritoneum. Arteries, veins, lymph vessels and nerves travel within the mesentery.
Large intestine (AKA large bowel) includes many sections along its 1.5-meter length, such as cecum and appendix, ascending colon, transverse colon, descending colon, sigmoid colon, rectum, and anal canal. Lymphatic drainage from the ascending colon and proximal two-thirds of the transverse colon is to the colic lymph nodes and the superior mesenteric lymph nodes, which drain into the cisterna chyli. The lymph from the distal one-third of the transverse colon, the descending colon, the sigmoid colon, and the upper rectum drain into the inferior mesenteric and colic lymph nodes. The lower rectum to the anal canal above the pectinate line drain to the internal iliac nodes. The anal canal below the pectinate line drains into the superficial inguinal nodes.
Moreover, the immunological function of the intestinal tract is also associated with the complex community of microorganisms called gut flora or gut microbiota. For example, the large intestine houses over 700 species of bacteria that perform a variety of functions, as well as fungi, protozoa, and archaea. The amount of microbes in a human distal gut is in the vicinity of 100 trillion. In humans, the gut flora is established at one to two years after birth, and by that time, the intestinal epithelium and the intestinal mucosal barrier that it secretes have co-developed in a way that is tolerant to, and even supportive of, the gut flora and that also provides a barrier to pathogenic organisms. Some human gut microorganisms benefit the host by fermenting dietary fiber into short-chain fatty acids (SCFAs), such as acetic acid and butyric acid. Intestinal bacteria also play a role in synthesizing vitamin B and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics. The systemic importance of the SCFAs and other compounds they produce are like hormones, and the gut flora itself appears to function like an endocrine organ. Dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions.
People tend to underestimate the importance of gut flora, which plays many key roles. The gut flora community defends against pathogens by fully colonizing the space, making use of all available nutrients, and by secreting compounds that kill or inhibit unwelcome organisms that would compete for nutrients with it. It develops and maintains the intestinal epithelium and inducing antibody production. It helps to metabolize otherwise indigestible compounds in food The gut flora may even train and develop the immune system.
Surprisingly, recent study shows that biochemical signaling can take place between the gastrointestinal tract and the central nervous system, via the so-called “gut-brain axis”. The gut-brain axis includes the central nervous system, neuroendocrine and neuroimmune systems including the hypothalamic-pituitary-adrenal axis (HPA axis), sympathetic and parasympathetic arms of the autonomic nervous system including the enteric nervous system and the vagus nerve, and the gut microbiota. As a bidirectional neurohumoral communication system, the gut-brain axis is important for maintaining homeostasis and is regulated through the central and enteric nervous systems and the neural, endocrine, immune, and metabolic pathways. The gut flora can produce a range of neuroactive molecules, such as acetylcholine, catecholamines, γ-aminobutyric acid, histamine, melatonin, and serotonin, which is essential for regulating peristalsis and sensation in the gut. Changes in the composition of the gut flora due to diet, drugs, or disease correlate with changes in levels of circulating cytokines, some of which can affect brain function. Likewise, chronic or acutely stressful situations activate the hypothalamic-pituitary-adrenal axis, causing changes in the gut flora and intestinal epithelium, and possibly having systemic effects. Additionally, the cholinergic anti-inflammatory pathway, signaling through the vagus nerve, affects the gut epithelium and flora. Hunger and satiety are also integrated in the brain. There may be a relationship between the gut flora and anxiety disorders and mood disorders including depression, schizophrenia, autism, Parkinson's disease, and obsessive-compulsive disorder.
That being said, it is critically important to sample and study the content in an intestinal tract. However, the human gut is largely unexplored, except for post mortem autopsies, which do not reflect much of the most important living dynamic phenomena and conditions. Many diseases with origin in human gut are of unknown causes, so only symptoms are treated. For example, the remote and inaccessible 15′ sections of intestines, beyond the 6 feet up and 6 feet down as viewed by endoscopy/colonoscopy instruments, remain unexplored in live humans. Even these upper and lower extremities that are viewed by camera can only be treated for visible damage, such as polyps or ulcers. A camera pill may be swallowed, and pictures are taken throughout the intestinal tract, but the information gleaned is largely qualitative. As such, quantitative in-vivo data and measurements are generally not available.
There is hence a serious need to analyze the biochemical, biological, physiological, and bioengineering processes taking place within the entire human intestinal tract, as precisely as in other anatomical systems (e.g. DNA, and microbiology). Advantageously, the present invention provides a sampling device capable of discontinuously and/or continuously sampling the content in human or animal intestinal tract, and a method thereof. The present invention enables an easy and convenient operation for collection and preservation of intestinal bio/chemical profile for external analysis, and measurements of many in vivo conditions. The invention can support medical professionals' decisions-making such as construction of mathematical, physiological, biochemical, and other engineering models; delineation of causes of diseases originating within the gut; and prescribing diets or medications.
One aspect of the present invention provides a catheter-shaped sampling device that can enter into a conduit, and can move along the conduit for sampling a content contained therein. The catheter-shaped sampling device includes:
In a representative embodiment, the catheter-shaped sampling device includes a continuous sample collector in one of the sampling channels, in addition to or as an alternative of, the discontinuous sample collector as described above.
Another aspect of the invention provides a process for sampling content in a conduit using the catheter-shaped sampling device as described above. The process includes the steps of inserting the flexible tube into the conduit; moving the flexible tube along the conduit; and collecting the content of the conduit at a targeted location with a discontinuous sample collector and/or a continuous sample collector.
The above features and advantages and other features and advantages of the present invention are readily apparent from the following detailed description of the best modes for carrying out the invention when taken in connection with the accompanying drawings.
The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements. All the figures are schematic and generally only show parts which are necessary in order to elucidate the invention. For simplicity and clarity of illustration, elements shown in the figures and discussed below have not necessarily been drawn to scale. Well-known structures and devices are shown in simplified form, omitted, or merely suggested, in order to avoid unnecessarily obscuring the present invention.
In the following description, for the purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It is apparent, however, to one skilled in the art that the present invention may be practiced without these specific details or with an equivalent arrangement.
Where a numerical range is disclosed herein, unless otherwise specified, such range is continuous, inclusive of both the minimum and maximum values of the range as well as every value between such minimum and maximum values. Still further, where a range refers to integers, only the integers from the minimum value to and including the maximum value of such range are included. In addition, where multiple ranges are provided to describe a feature or characteristic, such ranges can be combined.
The term “conduit” is intended to include a biological conduit, an industrial conduit, or any combination thereof. Examples of the biological conduit include, but are not limited to, human or animal intestinal tract or gut, gastrointestinal tract, buccal cavity, pharynx, esophagus, stomach, small intestine, duodenum, jejunum, ileum, large intestine, cecum, colon, rectum, anal canal, respiratory tract, upper respiratory tract, lower respiratory tract, nasal cavity, paranasal sinuses, pharynx, nasopharynx, oropharynx, laryngopharynx, larynx, trachea, bronchi (primary, secondary and tertiary), bronchioles (including terminal and respiratory), lungs (including alveoli), ear canal, vagina, cervix, uterus or womb, Fallopian tubes, ovaries, urinary tract, kidney, renal pelvis, ureter, urinary bladder, and urethra etc. Examples of the industrial conduit include, but are not limited to, various tubular structures in an industrial apparatus, equipment, a product, a machine, a production line, and the like.
The term “content’ as used herein may include human or animal gastrointestinal fluid, intestinal secretions, solid or semisolid, substances, slurry, feces, and stool etc.
In the following description, the invention will be illustrated and described using intestinal tract as a representative example. However, it should be appreciated that the invention may be applied to any other conduit structures for sampling the content therein, mutatis mutandis.
Referring now to
The catheter-shaped sampling device 10 of the invention may be built like a probe, a gastric feeding tube, a duodenal feeding tube, or a gastrostomy, among others. For example, the catheter-shaped sampling device 10 may be built like, and used like, a colonoscope, for inserting into the intestinal tract through a patient's anus as shown in
Referring to
As an alternative to, or in addition to, the discontinuous sample collector 14, a continuous sample collector 24 may be included in one of sampling channels 13. In various embodiments, continuous sample collector 24 generally employs a rolling belt design to collect the intestinal content.
In an embodiment as shown in
Rollers 111 and 112 work together like twin roller strip caster, in which the two rollers have parallel axes and are spaced apart from each other by a distance corresponding to the desired thickness of the cast strip. Content 140, like ingot steel, is fed or supplied to the gap between two oppositely-rotating casting rolls 111 and 112, forming a sheet-like sample that can be rolled into sample depository 141.
The first convoy belt 121 is so configured that, in a sampling operation, it extends from the first belt source 131 to the first cylindrical roller 111. Then, it contacts the roller 111 with its first back surface 121b. While belt 121 is winding around the roller 111, the first sampling surface 121s is exposed to the content 140 in the conduit. Sampling surface 121s is loaded (or absorbed) with a portion of the content 140 by adhesion. At last, convoy belt 121 carries the loaded content 140 to a sample depository 141. Sample depository 141 stores the samples.
The second convoy belt 122 works in a manner similar to belt 121. Belt 122 operates in a symmetrical manner with belt 121. It is configured to extend from the second belt source 132 to the second cylindrical roller 112, to contact the roller 112 with the second back surface 122b, to wind around the second cylindrical roller 112, to expose the second sampling surface 122s to the content 140 in the conduit, to load the content 140 on the second sampling surface 122s, and to carry the loaded content 140 to the sample depository 141.
Therefore, the contents 140 on surfaces 121s and 122s will meet each other and be properly squeezed together when belts 121 & 122 pass the gap between two rollers 111 & 112. The gap is configured to be narrower than the thickness of combined belts 121 & 122 with content 140, so that content 140 is completely squeezed (but not over squeezed it to cause content oozing out) between the two surfaces 121s and 122s, and completely loaded on, or sandwiched/encapsulated between, both surfaces. Then belts 121 & 122 both pass through the gap between rollers 111 and 112, and carry the loaded content 140 to the sample depository 141. Such a “sandwich” or “encapsulation” configuration helps to preserve the sample 140's in-vivo environmental integrity, and to prevent cross contamination between different samples on the same belt. At last, the two convoy belts 121 & 122 loaded with the combined contents 140 are pulled at a same, speed toward the sample depository 141.
As shown in
A manual or powered collector driver 150 may be configured to pull the two convoy belts (121, 122) loaded with the combined contents 140 at a same speed toward the sample depository 141. The sampling device of the invention may further include a controller 160 to manage the operation of the device. If necessary, a vacuum system (not shown) may be employed to suck the intestinal content into channel 13 through its opening 1301.
The convoy belts (121, 122) used in the present invention is preferably motor-driven, thin, and sterile ribbon-belt. Samples from different sections of the intestinal tract can be collected into different locations of the convoy belts.
In a specific embodiment as shown in
In various embodiments, the convoy belt 121/122 of the invention may include two layers joined together, a substrate layer having a back surface as described above, and an adsorbent layer having a sampling surface as described above. As shown in
In a preferred embodiment as shown in
In an embodiment, convoy belt 122 as described above may be a simple covering belt with no adsorbent layer 12a, and such a covering belt may simply be used to seal, cover, or encapsulate belt 121 that is loaded with intestinal sample 140.
In some embodiments, belt 121 may function as a sample wipe or a sample trap. It may be made of paper, cotton cloth or porous PTFE (Teflon), for example, an open weave fiberglass fabric coated with a layer of PTFE.
The present invention also provides a process for sampling content in a conduit using the catheter-shaped sampling device. The position of the sampling device may be monitored with ultrasound, X-ray, magnetic resonance imaging (MRI), or other means, and when the device reaches a predetermined position/section of the intestinal tract, the device may start collecting samples along the pathway in the intestinal tract. As shown in
The sample depository 141 with the collected sample 140 is subsequently sent or handed over to a medical institution or laboratory, where the sample is analyzed. The loaded belt 121 or belts 121/122 may mirror the content of at least a segment of the intestinal tract along its length, and can be cut into pieces to establish the spectrum of intestinal content in that segment. Referring to
The individual hairs 1402 and the pieces in
In the foregoing specification, embodiments of the present invention have been described with reference to numerous specific details that may vary from implementation to implementation. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense The sole and exclusive indicator of the scope of the invention, and what is intended by the applicant to be the scope of the invention, is the literal and equivalent scope of the set of claims that issue from this application, in the specific form in which such claims issue, including any subsequent correction.
