A device with alternatingly wound retrieval threads for collecting cells.

Abstract

A swallowable device for collecting cells, comprising: a swallowable capsule; a retrieval thread, the retrieval thread being connected to the swallowable capsule at its distal end, with the distal end of the thread connected to an applicator device; and a portion of the thread being bundled together with the swallowable capsule, the portion being wrapped around the thread in a bundled manner from the distal end of the portion to the proximal end of the portion, such that there is no net twist around the thread.

Description

[[BACKGROUND ART]]

[0001] Esophageal cancer is one of the most common types of cancer globally, causing an estimated 500,000 deaths worldwide each year. As with other forms of cancer, treatment for esophageal cancer is most effective when the cancer is identified at an early stage. However, it can be difficult to identify symptoms of esophageal cancer.

[0002] One potential warning sign of esophageal cancer is a condition called Barrett's esophagus. This is a condition in which cells in the patient's esophagus begin to grow abnormally or change. Although Barrett's esophagus is closely associated with esophageal cancer, only a small number of cases of Barrett's esophagus progress to esophageal cancer. By identifying cases of Barrett's esophagus, patients at risk of developing esophageal cancer can be identified, and these patients can then be proactively monitored or treated.

[0003] Several methods exist for identifying Barrett's esophagus. Endoscopy can be used to examine the inside of the esophagus for Barrett's esophagus, but it is expensive, time-consuming and invasive. In recent years, an alternative method for identifying Barrett's esophagus, known as the Cytosponge-TTF3 test, has been developed. This test uses a device called a cytosponge to collect cell samples from the patient's esophagus. The cell sample is then processed using a so-called TTF3 laboratory test to identify Barrett's esophagus from biomarkers in the sample.

[0004] The cytosponge device consists of a swallowable capsule containing a small, soft sponge attached to a retrieval cord. Before use, the capsule and cord are removed from the blister pack. Optionally, the capsule, along with a bundled length of cord, is administered either by a trained healthcare professional or handed to the patient to swallow. Once swallowed, the capsule travels down the esophagus as the bundled cord unfolds. The capsule may travel all the way down to the stomach or be held somewhere in the middle of the esophagus. There is then a pause (typically several minutes) while the capsule dissolves and releases the sponge, which then expands. The expanded sponge is then pulled out by lifting the cord. As the sponge is pulled out, it rubs against the esophageal wall, thereby collecting a cell sample. After the sponge is retrieved from the patient, it is sent to the laboratory where a TFF3 test is performed. The cytosponge-TTF3 test is faster and easier to administer than endoscopy and requires less complex equipment and training to perform. This will allow more patients to be tested for Barrett's esophagus more quickly and inexpensively. However, there are some problems associated with cytosponge devices known in this field.

[0005] The delivery and swallowing of cytosponge devices can be difficult and known to be distressing for some patients. Similar to the innate aversion to swallowing foreign objects, humans have a gag reflex (also known as the pharyngeal reflex) that can be triggered when an unusual object is swallowed or touches a specific area of ​​the mouth. The gag reflex can cause patients to involuntarily expel the capsule as it moves down the throat or towards the back of the mouth. Therefore, there is a need for capsule sponge devices that can be administered more comfortably and efficiently for patients. [Overview of the project] [Problems that the invention aims to solve]

[0006] According to the first example, a swallowable device is provided for collecting cells, comprising a swallowable capsule and a retrieval thread connected to the swallowable capsule at its distal end, wherein the proximal end of the thread is configured to be connected to an applicator device, and a portion of the thread is bundled together with the swallowable capsule, the bundled portion of which includes a plurality of turns around one or more winding axes, and the direction of the turns around one or more winding axes alternates between each consecutive turn. [Means for solving the problem]

[0007] The winding axis may be a virtual axis, meaning that it does not need to be defined by the axis of the physical surface on which the thread is wound.

[0008] In a simple coil, the thread is wound continuously in the same direction, so it unwinds back into itself and forms a helix. Also, in threads of length that are bundled tightly and randomly with no room for error, a long range of threads will almost certainly be bundled in a helical shape. The pitch of the helix causes twisting of the thread, resulting in a twist. The inventors have found that when a swallowable device for collecting cells, which includes a coil or random bundle of threads, is released in the mouth or throat, the release of this twist can cause the threads to become entangled. This can prevent the capsule from moving smoothly from the esophagus to the stomach. In addition, the twist of threads contained in a conventional coiled bundle can cause the bundle to expand in all directions when released. When the bundle is released at the back of the patient's mouth, the bundle can become entangled in the patient's teeth or wrap around the swallowable capsule, preventing the device for collecting cells from deploying correctly and / or causing discomfort to the patient. Because the retrieval thread may not be able to maintain consistent tension along its length, entanglement can also make it difficult to retrieve swallowed capsules.

[0009] Alternating the winding direction between consecutive turns of the first bundled portion of the retrieved thread prevents twisting from building up in the thread and reduces the risk of entanglement when the thread is released. The twist introduced to the thread by the first direction of winding (e.g., clockwise winding) is offset by the next or subsequent winding in the opposite direction (e.g., counterclockwise winding). As a result, the overall twist of the thread is minimized. This allows the device for collecting cells to be deployed more efficiently and comfortably. The capsule moves smoothly down the patient's throat, avoiding reflex movements caused by the thread entanglement and unraveling. The smoother unraveling of the bundled portion ensures that the capsule deploys to the correct distance in the esophagus or stomach, allowing for sample collection.

[0010] During use, the distal end of the thread is swallowed with the capsule, while the proximal end of the device for collecting cells can be held by the operator (either the patient themselves or another person such as a doctor or nurse). In other words, the proximal end of the thread is proximal to the operator during use, and the distal end is distal to the operator during use. The proximal end of the thread may be configured to connect to the applicator device by including a certain length of thread not included in the bundled portion, which may be tied to or fixed to the applicator device during use.

[0011] Preferably, the number of turns in the first direction is no more than one of the number of turns in the opposite second direction. When the number of turns in each direction is equal, the twist caused by each turn is canceled out by the opposite twist caused by the corresponding reverse turn, so the net twist of the yarn is zero. However, in some examples, for practical reasons, it may be more convenient to have an additional turn in one direction. For example, the length of a portion of bundled yarn may result in an unequal number of turns in each direction, such as 10 clockwise turns and 11 counterclockwise turns.

[0012] Optionally, each winding is wrapped around an angle of less than 180 degrees, so that a portion of it forms a concertina configuration known as a zigzag configuration. In a concertina configuration, the bundled threads do not self-cross but rather form an undulating path. Each winding is wrapped around a spatially different winding axis. The threads in the concertina bundle may be bundled in a plane such that their normals to the plane are parallel to the winding axes.

[0013] Optionally, each winding is wound over an angle of 180 to 360 degrees such that a portion of it includes a figure-eight configuration. Because each winding exceeds 180 degrees, the yarn self-crosses in a bundled state, forming a figure-eight. Winding in one direction is wound around a first winding axis, and winding in the opposite direction is wound around a second winding axis spatially offset from the first axis. The yarn can be wound continuously from one winding axis to the other to form a stacked figure-eight configuration.

[0014] The figure-eight bundle offers several advantages over other bundle configurations. The process of creating the figure-eight pattern involves relatively simple alternating loops of yarn, which can be automated for mass production up to larger scales. This can lead to lower production costs and consistent bundle results. The figure-eight pattern can also distribute stress and tension more evenly along the length of the yarn. This reduces the risk of twisting caused by stretching or bending. The loops in the figure-eight pattern provide natural pivot points, making it easier to bend the bundle and feed it in tight spaces without putting excessive strain on the yarn. The figure-eight bundle can also inherently offer a certain level of strain relief due to its loop design. This can help prevent damage to the yarn caused by movement or friction when the yarn is wound or unwound.

[0015] Figure-eight bundles also offer advantages compared to concertina bundles. Due to the simpler looping method required, figure-eight bundles can be easier and more cost-effective to manufacture than concertina bundles. Figure-eight bundles tend to be less prone to tangling than concertina bundles. The structured loops prevent the threads from intertwining and reduce the likelihood of knots and snags when the threads are wound or unwound. Figure-eight bundles may be more space-efficient than concertina bundles because they allow the loops to be bundled compactly while maintaining flexibility, which can be advantageous in applications with limited space, such as applicators.

[0016] In another example, the yarn can be wound in a braided pattern that is effectively an enlarged figure eight. This involves winding the yarn in a first winding axis with a first winding over an angle of 180–360 degrees, then around a second winding axis with less than 180 degrees, and then around a third winding axis with windings of 180–360 degrees, where the direction of winding alternates between each consecutive winding (for example, the windings around the first and third winding axes are clockwise, and the windings around the second winding axis are counterclockwise). This braided pattern can be enlarged with each additional winding axis, where the first and last winding axes are wound with windings of 180–360 degrees, and the intervening axes are wound with windings of less than 180 degrees.

[0017] In both the concertina and figure-eight configurations, each winding is followed by a winding in the opposite direction around a different winding axis. This ensures that there is no net construction of twist in the yarn.

[0018] It will be understood that the yarn may be wound in any other preferred pattern, which includes a series of windings around one or more virtual winding axes, where the direction of winding around the axis alternates between successive windings.

[0019] Preferably, one or more winding shafts are multiple winding shafts oriented parallel or substantially parallel to each other; that is, all winding shafts extend in the same direction. This can simplify the manufacturing of the bundled portion.

[0020] A further example includes a swallowable device for collecting cells, comprising: a swallowable capsule; a retrieval thread, the distal end of which is connected to the swallowable capsule, with the distal end of the thread being configured to be connected to an applicator device; and a portion of the thread, which is configured to be bundled together with the swallowable capsule, the portion of which is wound around the capsule in an over-under configuration.

[0021] In conventional helical coils, the yarn is wound continuously over itself, with the proximal end of the yarn in each loop of the coil (i.e., the end of the loop closest to the proximal end of the yarn along the yarn) passing adjacent to the distal end of the yarn in the loop (i.e., the end of the loop closest to the distal end of the yarn along the yarn), and the same applies when the yarn is wound from distal to proximal. This is simply an alternative way of defining the pitch of the helix formed by the coil. In an over-under configuration (sometimes called a reverse coil configuration or flip coil configuration), the yarn is wound alternately around the winding axis in over-loops and under-loops, with the proximal end of the yarn in the over-loop passing adjacent to the distal end of the yarn in the loop, and in the under-loop, the proximal end of the yarn is wound beneath the distal end of the yarn in the loop.

[0022] The over-under configuration also minimizes twisting of a portion of the retrieved yarn. The yarn twists in a first direction around its length in the over-loop, inducing a twist in the first direction, but this is offset by the subsequent under-loop, which twists the yarn in the opposite direction, resulting in a reverse twist. Thus, the over-under configuration constitutes an alternative example of the present invention that provides the same technical effect to solve the same problem identified by the inventors.

[0023] In a further example, a swallowable device for collecting cells is provided, comprising: a swallowable capsule; a retrieval thread, the retrieval thread being connected to the swallowable capsule at its distal end, with the distal end of the thread being connected to an applicator device; and a portion of the thread being bundled together with the swallowable capsule, the portion being wrapped around the thread in a bundled manner from the distal end of the portion to the proximal end of the portion, such that there is no net twist around the thread.

[0024] A further example includes a swallowable device for collecting cells, comprising: a swallowable capsule at least partially filled with a weighting material; a retrieval thread configured such that the distal end of the thread is connected to an applicator device, with the distal end of the thread connected to the swallowable capsule; and a portion of the thread configured to be bundled together with the swallowable capsule.

[0025] Swallowable capsules and their contents may have low density, meaning their weight is low compared to any resistance forces during swallowing (e.g., frictional forces as the capsule moves through the esophageal wall or other particles / fluids in the esophagus). These resistance forces therefore significantly affect the capsule's trajectory during swallowing, potentially increasing its time in the esophagus or even causing blockage, in either case causing discomfort to the patient. By including weighting material within the capsule, its weight is increased without significantly increasing its volume, ensuring the capsule descends the throat without slowing down under resistance or deviating from its trajectory. Increased capsule weight compared to the retrieval thread also increases the tension on the retrieval thread as the capsule is swallowed and retrieved. This reduces the likelihood of the bundle expanding laterally and / or becoming entangled around itself or another object.

[0026] Preferably, the weighting material comprises polyethylene glycol. Polyethylene glycol is non-toxic, inert and water-soluble, which means that it can be harmlessly released into the body when the capsule is opened.

[0027] Preferably, the capsule accommodates an abrasive material for collecting cells, preferably a sponge material. The swallowable capsule may be configured to dissolve or open to release the abrasive material after a certain period of time in the patient's body, or when the capsule reaches a specific part of the esophagus or stomach. The abrasive material is then used to scrape cell samples from the inner wall of the body. The sponge material can also absorb liquid samples from the body such as mucus or gastric acid.

[0028] Preferably, the distal end of the recovery thread is connected to the contents of the capsule, such as the aforementioned abrasive material, such that when the solid capsule dissolves or opens, the contents are held at the distal end of the recovery thread and can thereby be pulled out over the esophagus.

[0029] Preferably, a portion of the bundled state is arranged along the thread proximal to the distal end of the thread, or adjacent to the distal end of the thread. This ensures that the bundled portion can be easily swallowed together with the capsule, preferably in a single swallowing action.

[0030] Preferably, a portion of the recovery thread has a length of at least 450 mm. This allows the capsule to be dropped all the way down to the patient's throat while keeping the proximal end of the thread held outside the patient's mouth.

[0031] In a further example, there is provided a packaging device for administering to a patient a swallowable device for collecting cells, comprising: the swallowable device for collecting cells described herein; and an applicator device connected to the proximal end of the recovery thread, configured to releasably accommodate the device for collecting cells and a portion of the recovery thread, for direct administration to a patient.

[0032] Optionally, the applicator device may be equipped with a mechanical release mechanism for dispensing the device for collecting cells, facilitating the smooth deployment of the device for collecting cells without twisting or deforming the bundled retrieval threads.

[0033] Further examples include a method for administering a swallowable device for collecting cells as described herein, comprising the steps of: inserting a bundle and a capsule into the mouth of a patient; allowing the patient to swallow the capsule and bundle while holding the distal end of the retrieval thread; collecting a cell sample from the internal region of the patient using the swallowable capsule; and retrieving the swallowable capsule by pulling the distal end of the retrieval thread out of the patient's mouth.

[0034] A further example provides a method for manufacturing a swallowable device for collecting cells, comprising the steps of: attaching a swallowable cell capsule to the distal end of a retrieval thread; and bundling a portion of the retrieval thread by winding multiple turns around a winding axis, with each consecutive turn alternating the direction of winding around the winding axis. These steps may be performed in an order different from the order in which they are set. For example, the thread may be bundled before the distal end of the thread is attached to the swallowable capsule.

[0035] To attach a device for collecting cells to an applicator device, the method may further include the steps of housing a capsule and a portion of the retrieval thread within the applicator device, and connecting the proximal end of the retrieval thread to the applicator device. These steps may also be performed in a different order. For example, the proximal end of the retrieval thread may be connected to the applicator device before the device for collecting cells is housed within it.

[0036] Preferably, a portion is bundled using a winding device. The winding device simplifies the fabrication / assembly of the device for collecting cells because it allows the operator to wind the thread into the desired configuration more quickly and with greater reproducibility.

[0037] Optionally, the winding device comprises a pair of winding posts projecting parallel to the surface of the winding device so that the posts define a winding axis, and a portion of the material is bundled by winding an eight-shaped pattern around the winding posts.

[0038] Winding the figure-eight pattern may involve winding the retrieved yarn alternately in a first direction around a first winding post, and then winding the retrieved yarn in the opposite direction around a second winding post. For example, the yarn may be wound clockwise around the first winding post and counterclockwise around the second winding post.

[0039] The winding device may include notches or indentations on the surface of the winding device between the winding posts. This allows the operator to grasp the bundled yarn from the opposite side (using either fingers or a tool) in order to retrieve it from the winding device. The separation distance between the posts can be 1 cm to 3 cm in width, and the notches are of equal or narrower width. This provides sufficient space for the user's fingers to position themselves between the posts, allowing the user to grasp the yarn with their fingers and then remove it from the winding device.

[0040] Optionally, the winding device may instead comprise a pair of opposing trap regions, each having a width that includes a trap region providing interference engagement with the retrieved yarn and a gap separating the trap regions, the portion of which is bundled by winding the retrieved yarn with a concertina pattern that passes across the gap through the trap regions.

[0041] Alternatively, winding the concertina pattern may include, for each trap region, pulling the retrieved thread through the trap region from the inside facing the gap of the trap region to the outside of the trap region so that the thread is held in place by interference fitting with the trap region; pulling the retrieved thread back through the trap region from the outside to the inside of the trap region so that the thread is held in place by interference fitting with the trap region; and extending the thread across the gap to the inner surface facing the gap of other trap regions.

[0042] The gap may be 1 to 3 cm wide, allowing the user to insert their fingers into the gap and then pinch the bundled threads with their fingers to retrieve the bundle from the winding device.

[0043] Preferably, the winding device includes a capsule holder for positioning a swallowable capsule during winding. The capsule holder may actively hold the capsule in place by means of a clasp including, for example, an elastic member that grips the capsule or the distal end of the retrieval thread. Alternatively, the capsule holder may be a pocket or recess that conforms to the shape of the capsule or around the distal end of the retrieval thread to assist the user in positioning the capsule. For example, the user may place the capsule in the pocket and then use their fingers to hold the capsule in place while winding the retrieval thread.

[0044] A further example includes a method for manufacturing a packaging device for administering a swallowable device for collecting cells, the method comprising the steps of: attaching a swallowable cell capsule to the distal end of a retrieval thread; bundling a portion of the retrieval thread by winding a plurality of loops around a winding axis in an over-under pattern; housing the capsule and the portion of the retrieval thread in an applicator device; and attaching the proximal end of the retrieval thread to the applicator device.

[0045] Preferably, a portion is bundled using a winding device, the winding device comprising a winding surface that defines a winding axis and tapers from a wide end to a narrow end, and a capsule holder proximal to the narrow end of the winding surface, and a portion is bundled by winding the retrieved yarn around the winding surface in an over-under pattern.

[0046] The winding surface is tapered so that the end of the winding surface closest to the capsule's position becomes narrower during use. This allows the wound bundle to be removed from the winding device by sliding the bundle along the winding axis toward the narrow end of the winding surface, i.e., toward the capsule. Thus, the capsule and the wound bundle can be removed from the winding device by gripping them together and then pulling them apart from the narrow end of the winding surface.

[0047] The cell capsules, threads, winding patterns, and / or applicator devices used in the above-described method may have any of the optional features of such components described herein with reference to other examples of the present invention.

[0048] Further examples include various winding devices as described herein.

[0049] The applicator device may be elongated and / or have a handle at one end and means for housing a device for collecting cells and a portion of the retrieval thread at the opposite end. This may allow the operator to use the handle to position the device for collecting cells at the back of the patient's tongue, providing good control of the distal end of the applicator without requiring the operator to insert their fingers into the patient's mouth.

[0050] Providing a mechanical release mechanism for administering a device for collecting cells is advantageous because it allows the operator to release the device for collecting cells contained at the distal end of the applicator device via a control unit located at the proximal end of the applicator device. Thus, the operator can correctly position the distal end of the applicator device in the patient's mouth and then release the device for collecting cells without having to remove the applicator device or insert a finger into the patient's mouth.

[0051] Although the device is described in relation to cell collection for the TTF3 test, it will be understood that it is also suitable for other applications. For example, the device can also be used to collect cell samples or other materials from the esophagus for other types of tests, such as those used for cytological, histological, or molecular analysis. By providing a sufficiently long retrieval thread, it is ensured that the capsule travels all the way into the stomach before the sponge is released. The device can then be used to collect a sample of the stomach wall or contents (e.g., a sample of stomach acid) before it is retrieved by being pulled up over the esophagus.

[0052] In other embodiments, the probe may be released in a body cavity other than the mouth using appropriately adapted embodiments of the present invention. For example, the device for collecting cells may be inserted through the nostril to release the probe, which can then collect a sample from inside the nasal cavity or pharynx. In another example, the device for collecting cells may be inserted through the patient's anus to release the probe, which can collect a sample from the patient's rectum and / or sphincter. The design of the device for collecting cells may be adapted to different orifices. For example, the capsule of the device for insertion into the nostril for cell collection may be physically smaller than the capsule for insertion into the mouth, and the retrieval thread may be made of a shorter and thinner thread. The device for collecting cells may also be adapted for use in animal subjects. This may include, for example, using a more robust, swallowable capsule that can resist being bitten by the animal's teeth. [Brief explanation of the drawing]

[0053] [Figure 1] This shows a cross-section of a thread coiled in the conventional spiral manner. [Figure 2] This shows a device for collecting cells, including a portion of the retrieval threads bundled in a figure-eight configuration. [Figure 3a] The image shows a device for collecting cells, including a portion of the retrieval threads bundled into a concertina configuration, with a magnified view of the bundled portion to show its geometric shape. [Figure 3b] The image shows a device for collecting cells, including a portion of the retrieval thread bundled into a concertina configuration, and the bundle as it is packaged. [Figure 4a] The image shows a device for collecting cells, including a portion of the retrieval threads bundled into a concertina configuration, with a magnified view of the bundled portion to show its geometric shape. [Figure 4b] The image shows a device for collecting cells, including a portion of the retrieval thread bundled into a concertina configuration, and the bundle as it is packaged. [Figure 5] This flowchart illustrates a method for manufacturing a device for collecting cells, which is to be incorporated into a packaging system. [Figure 6a] This shows an isometric view of a winding device for use in manufacturing a device for collecting cells, having a figure-eight structure. Additionally, it shows the positions of the capsule and retrieval thread on each winding device in use. [Figure 6b] This shows an isometric view of a winding device for use in manufacturing a device for collecting cells, having a figure-eight structure. [Figure 7a] This shows an isometric view of a winding device for use in manufacturing a device for collecting cells, which has a concertina-like bundle of components. Additionally, it shows the positions of the capsule and retrieval thread on each winding device in use. [Figure 7b] This shows an isometric view of a winding device for use in manufacturing a device for collecting cells, which has a concertina-like bundle of components. [Figure 8a] This shows an isometric view of a winding device for use in manufacturing a device for collecting cells, having an over-under constituent bundle. Additionally, it shows the positions of the capsule and retrieval thread on each winding device in use. [Figure 8b] This shows an isometric view of a winding device for use in manufacturing a device for collecting cells, having an over-under constituent bundle. [Figure 9a] The images show a plan view and a side view of an example packaging device for releasing a device for collecting cells, respectively. [Figure 9b] The images show a plan view and a side view of an example packaging device for releasing a device for collecting cells, respectively. [Modes for carrying out the invention]

[0054] Referring to Figure 1, a section of the coiled thread 110 is shown. The thread 110 is coiled around a winding axis W, and the winding direction D is clockwise when viewed along the direction of the winding axis W. The coiling of the thread 110 induces a twist T around the axis 110a of the thread 110 itself. Since the thread 110 is elastic, the twist T of the thread induces a torsional force that acts in opposition to the twist T and returns the thread to an uncoiled state. With each turn of the coil, the thread 110 twists further, and the torsional force on the opposite side increases. For illustrative purposes, the thread is shown as having a polygonal cross-section rather than a circular one. The twist T of the cable can be seen from the angle α created between the winding axis W and the side 110b of the polygonal cross-section. When the thread 110 forms a coil around the winding axis W, the angle α increases from α1 to α2-α3 in a counterclockwise direction around the thread axis 110a due to the twist T.

[0055] Referring to Figure 2, an example of a device for collecting cells 200 is shown, comprising a capsule 201 attached to the distal end 210d of the retrieval thread 210. The proximal end 210p of the retrieval thread 210 is configured to be attached to an applicator device (not shown). A portion 211 of the retrieval thread 210 is bundled into a configuration having multiple turns in alternating directions around each winding axis. In the example shown in Figure 2, this is a figure-eight configuration. In the figure-eight configuration, the bundle consists of 180–360 degree turns 203 that are alternately wound around a first winding axis 202a and a second winding axis 202b. The winding axes 202 are perpendicular to the page, substantially parallel to each other, and defined as the page points. The turns 203a around the first winding axis 202a are counterclockwise, and the turns 203b around the second winding axis 202b are clockwise. Multiple windings 203 are wound around each of the winding axes 202, with each winding 203 being in an alternating direction, preceded by the first winding 203. As a result, the net twist of the retrieval thread 210 is minimized at any point along its length. Therefore, when the device for collecting cells is released, the bundled portion 211 is more likely to unravel smoothly along its entire length without becoming entangled.

[0056] Capsule 201 (contents not shown) contains a sponge packaged within a retractable housing or casing. In a preferred embodiment, when closed, capsule 201 has a length in the range of 23–24 mm, smaller than a standard-size capsule known to be easily swallowed by most patients. The capsule may have an internal volume of at least 1 ml, providing space for the sponge. The capsule casing may be translucent or opaque so that the patient is not distressed by seeing the sponge contained inside when preparing to ingest capsule 201. The capsule wall may be formed from hydroxypropyl methylcellulose (HPMC) or other non-toxic material. Once swallowed and ingested into the stomach, the capsule wall dissolves or cracks open, releasing the sponge. The capsule wall may be formed as a single piece, or alternatively, the capsule wall may be formed from multiple components that allow it to crack open. Similar to the sponge, capsule 201 may contain a weighting material such as polyethylene glycol to increase the overall density of the capsule and provide sufficient weight to smoothly descend the patient's esophagus.

[0057] The retrieval thread 210 may be formed from polyester surgical suture or other non-toxic material. The thread 210 may be formed from a single thread or from multiple threads braided together. The retrieval thread 210 may have a total length ranging from 10 cm to 40 cm. The capsule 201 may have a small opening through which the retrieval thread 210 can pass and connect to the sponge. In some examples, the sponge may be connected to the retrieval thread 210 during assembly, and then the capsule may be formed around the sponge and the thread 210 so that the capsule is formed around the thread 210 without an opening.

[0058] Referring to Figures 3a and 3b, another example of a device for collecting cells 300 is shown, comprising a capsule 301 attached to the distal end 310d of a portion of the retrieval thread 310. The proximal end 310p of the retrieval thread 310 is configured to be attached to an applicator device (not shown). The portions 311 of the retrieval thread 310 are bundled into alternating configurations having multiple turns in alternating directions around each winding axis. In the example shown in Figure 2, this is a zigzag or concertina configuration. In the concertina configuration, the bundle consists of approximately 180 degrees of turns 303 that are alternately wound around a first set 302a and a second set 302b of winding axes. The winding axes 302 are perpendicular to the page, substantially parallel to each other, and defined as the page points to. The windings 303a around the first set of winding axes 302a are counterclockwise, and the windings 303b around the second set of winding axes 302b are clockwise. Note that the winding axes 303 may be virtual and / or held in the configuration without physical axes extending through the windings, in order to achieve the concertina configuration, in the sense that the yarn 310 is not necessarily wound around a physical surface. Due to the length of the yarn 310 in the example shown, there are three clockwise windings 303a and four counterclockwise windings 303b. Other examples may include any number of windings, but it will be understood that the number of windings in one direction is preferably close to the number of windings in the opposite direction in order to minimize net twisting. More preferably, the number of windings in the first direction is equal to the number of windings in the opposite direction, or no more than one of the number of windings in the opposite direction. Multiple windings 303 are wound around each of the winding axes 302, with each winding 303 being in an alternating direction, preceded by the winding 303 that follows. As a result, the net twist of the retrieved yarn 310 is minimized. Since the winding axes 302 of each set of winding axes 302a and 302b are parallel and aligned along a straight line, the bundled portion 311 is flat and forms a regular pattern. This further minimizes twisting of the bundled portion 311. Figure 3a shows an enlarged concertina configuration to more clearly show the positions of the winding axes 302a and 302b.During use, the bundled portions are preferably arranged in a more compact configuration, as shown in Figure 3b, with alternating windings in contact with each other along their length.

[0059] Referring to Figure 4, another example of a device for collecting cells 400 is shown, comprising a capsule 401 attached to the distal end 410d of a portion of the retrieval thread 410. The proximal end 410p of the retrieval thread 410 is configured to be attached to an applicator device (not shown). A portion 411 of the retrieval thread 410 is bundled in an over-under configuration. As can be seen in Figure 4b, in the over-under configuration, the bundle 411 includes alternating over-loops 403a and under-loops 403b. In the over-loop 403a, the proximal end of the loop thread passes over the distal end of the loop thread, in the sense that at the intersection of the over-loop 404a, the proximal end of the loop thread is above the distal end of the loop thread with respect to the plane of the page. In the underloop 403b, the proximal end of the loop's thread passes beneath the distal end of the loop's thread at the underloop intersection 404b, meaning that the proximal end of the loop's thread is below the distal end of the loop's thread relative to the plane of the page. Each overloop 403a twists the thread in one direction around its axis, inducing a twist. However, each successive underloop 403b twists the thread in the opposite direction around its axis, canceling out the twist.

[0060] For the sake of clarity, only a single overloop and a single underloop are shown in Figure 4a, but in other examples, bundle 411 may include multiple sequentially alternating overloops 403a and multiple underloops 403b.

[0061] In use, the bundle 411 may look like a conventional wound coil, as shown in Figure 4b. The overloop 403a and underloop 403b can be wound around a common winding axis 402 using known winding techniques for winding over-under configurations, such as those used for winding electrical cables. However, by carefully unwinding the bundle 411, it becomes possible to see the over-under configuration in Figure 4a.

[0062] 500 examples of methods for manufacturing devices for collecting cells are described below with reference to Figure 5.

[0063] In step 501, the swallowable cell capsule is attached to the distal end of the retrieval thread.

[0064] In step 502, a portion of the recovered yarn is bundled. In some examples, a portion of the recovered yarn is bundled by winding multiple loops around one or more winding axes, with each successive winding alternating the direction of winding around the winding axis 502. This can produce either a concertina or figure-eight bundle configuration, depending on whether the winding angle is greater than 180 degrees (figure-eight) or less (concertina). In other examples, the yarn is bundled in an over-under configuration, as described above 502. A winding device may be used to facilitate the bundling step.

[0065] In step 503, the bundle is positioned with the capsule as a device for collecting cells (e.g., proximal or adjacent to the capsule) and is ready for connection and / or insertion into the applicator device. The bundle may be found to be approximately the same length as the capsule to facilitate holding or packaging the bundle along the capsule.

[0066] In step 504, to form the packaging device, the proximal end of the retrieval thread is connected to the applicator device. In step 505, the device for collecting cells containing the capsule and the bundled portion are housed within the applicator device and ready for deployment. It will be understood that steps 503-505 are optional. For example, in some embodiments, only steps 501-503 may be performed to provide a cell collection device separated from the applicator device.

[0067] Figures 6a to 8b show examples of winding devices 600, 700, and 800 for use in winding a bundled portion of the retrieved yarn, as described in step 502 of method 500.

[0068] Figures 6a and 6b show a winding device 600 for winding a portion of a yarn in a figure-eight pattern. The winding device 600 comprises a pair of winding posts 606 onto which the retrieved yarn 610 is wound in a figure-eight pattern. In other words, the central axis of each winding post 606 defines the winding axis as the yarn is wound. In some examples, the yarn is wound clockwise around the first winding post 606a and counterclockwise around the second winding post 606b. The winding posts 606 are tapered so as to allow the yarn 610 to be easily pulled away from the posts 606 once it has been wound into a bundle. After the yarn 610 has been wound, the yarn may be removed from the winding device 600, and it will be understood that the alternating windings are defined around a virtual winding axis.

[0069] The capsule holder 605 is used to position the capsule 601 and to keep the capsule in place while the thread is being wound around it. The capsule holder 605 has a recess that is substantially the same shape as the capsule 601, into which the capsule can be fitted. A hole 605a on the back of the capsule holder 605 allows the user to push the capsule out of the recess while the thread 610 is being wound around the bundle.

[0070] The winding device 600 includes notches 607 that allow the user to pinch the bundled threads 610 from the top and bottom in order to remove the bundled threads 610 from the winding device while maintaining the figure-eight configuration. The notches 607 are larger than the width of the user's fingers (e.g., 1 cm to 3 cm) to provide space for the user's fingers.

[0071] Figure 7 shows a winding device 700 for winding a retrieved yarn in a concertina pattern. The winding device 700 comprises a pair of opposing trapping areas 706a, 706b. The trapping areas 706 are opposite in the sense that they face each other and are separated by a gap 706. Each trapping area 706 has a slot sized to provide interference engagement with the retrieved yarn. That is, the sides of the slots in the trapping area 706 grip the yarn 710 tightly enough to prevent the yarn 710 from slipping out of the slot, sliding along the slot, or accidentally falling out, but not so tightly as to prevent the yarn from being pulled through the slot during winding or during retrieval of the wound bundle from the winding device 700. In the example shown, both trapping areas 706 are positioned along an arm 708 that curves backward so that the trapping areas 706 face each other. In other examples, the trapping areas 706 may be positioned on separate arms.

[0072] A capsule holder 705, molded to the profile of the capsule 701, is used to hold the capsule 701 in place while it is bundled. The slot has a common open end 709 facing the capsule holder 705.

[0073] Winding the concertina pattern may first involve pulling the retrieved thread 710 through the first trap region 706a from the inside facing the gap of the trap region 706a (i.e., the inside of the arm 708) to the outside of the trap region (i.e., the outside of the arm 708) so that the thread 710 is held in place by interference engagement with the trap region 706a; pulling the retrieved thread back through the trap region 706a from the outside to the inside so that the thread 710 is held in place by interference engagement with the trap region 706a; and extending the thread 710 across the gap 707 to the inner surface facing the gap of the second trap region 706b. This process is then repeated, alternating between the first 706a trap region and the second 706b trap region until the concertina pattern is wound around part or all of the length of the slot of the trap region 706. Next, the user uses their fingers to grasp a bundled portion of the threads extending between the trapping sections 706 and pulls the bundled portion out from the common open end 709 of the slot to maintain the concertina configuration.

[0074] Figure 8 shows a winding device 800 for winding a bundle in an over-under pattern. The winding device 800 includes a capsule holder 805 configured to provide interference engagement with the retrieved yarn 810. The distal end of the yarn 810 proximal to the capsule 801 is inserted into the capsule holder 805, thereby obstructing the movement of the capsule 801. The winding surface 806 of the winding device defines the winding axis 803. The winding surface 806 tapers from a wide end 806b to a narrow end 806, with the capsule holder 805 proximal to the narrow end 806a. The retrieved yarn 810 is wound around the winding surface 806 in an over-under pattern. To remove the bundled portion 811 of the retrieved yarn 810 from the winding device 800, the user slides the bundled portion 811 of the yarn 810 toward the narrow end 806a of the winding surface 806, i.e., toward the capsule holder 805. The tapering of the winding surface 806 facilitates the easy removal of the wound bundle 811.

[0075] Referring to Figure 9, an exemplary packaging device 900 comprises a device 900b for collecting the above-mentioned cells and an applicator device 900a for administering device 900b. The applicator device 900a comprises an elongated body 901 and a slider 902. The body 901 has a handle 901a at its proximal end, allowing the user to precisely position the applicator device 900a in the mouth. The slider 902 is configured to slide relative to the body 901 of the applicator device 900a. In a preferred embodiment, the applicator device 901 is substantially larger than a capsule of size 000, which is the maximum size of a capsule that can be easily swallowed. This ensures that the applicator device 900a itself is not accidentally swallowed or lost in the patient's mouth. All parts of the device 900 are configured to lack sharp edges that could cause discomfort or injury to the patient.

[0076] The capsule 908 and the retrieval thread 910 work together to form a swallowable device 900b for collecting cells. The bundled portion 911 of the capsule and retrieval thread 910 is not visible in the plan and side views before deployment and is therefore indicated by a dotted line. The retrieval thread 910 connects the capsule 908 to the applicator device 900a, allowing the applicator device to be used to pull the sponge back from the patient. The proximal end of the thread 910 is connected to the applicator device 900a so that the thread 910 is securely attached to the applicator device 900a but does not hinder the deployment of the thread 910 as slack is stretched.

[0077] The swallowable capsule 908 is packaged together with a bundled portion 911 of the retrieval thread 910 in a chamber 905 at the distal end of the body 901 of the applicator device 900a. In the example shown, the bundled portion 911 is in a figure-eight configuration, but in other examples, the bundled configuration may be a concertina or over-under configuration, as previously described. During use, the bundled portion 911 of the thread 910 is released along with the capsule 908 at the back of the patient's tongue, toward the opening to the esophagus, sufficiently away from the patient's teeth or the applicator device 900a itself. This reduces the risk of the thread becoming entangled before or during ingestion. The bundled portion 911 is located on the side of the capsule 908 within the chamber 905, and when released, it reduces the risk of the thread becoming entangled with the capsule 908. The length of the thread 910 bundled in part 911 can be at least 450 mm, providing sufficient length for the sponge to move down the entire length of the esophagus and enter the stomach.

[0078] The walls of chamber 905 may be formed by an upper chamber wall 904a on the main body and a lower chamber wall 904b on the slider 902. While the slider 902 is fully extended (i.e., translated toward the distal end of device 900a), the capsule 910 and the bundled portion 911 of the thread 910 are housed and held within chamber 905. To release the capsule 908 and the portion 911 of the thread 910, the slider is retracted to open chamber 905 (i.e., translated toward the proximal end of device 900a). The upper chamber wall 904a on the main body 901 holds the capsule in place as the lower chamber wall 904b retracts together with the slider 902.

[0079] The slider 902 may be equipped with a thumb grip 903a at its proximal end, which is configured to slide along a groove 903b in the handle 901a of the body 901. By pulling back the thumb grip 903a with the thumb (or with any other fingers according to the operator's preferred grip on the handle 901a), the operator can slide the thumb grip 903a from a forward, retracted position to a rearward, released position, thereby retracting the slider 902.

[0080] The method of administration is described in detail below. First, the device 900 is partially inserted into the patient's mouth with the distal end of the applicator device 900a, including the chamber 905, positioned behind the patient's teeth, and the proximal end of the applicator device 900a positioned outside the patient's mouth in front of the patient's anterior teeth. The device 900 is positioned so that the handle 901a of the main body 900a protrudes from the patient's mouth, allowing the operator to grasp the handle 901a without needing to insert their hand or fingers inside the patient's mouth.

[0081] Once the device 900 is in place, the operator (typically a clinician such as a nurse) slides the thumb grip 903a backward along the groove 903b, thereby retracting the slider 902. This causes the lower chamber wall 904b to retract, opening the chamber 905. The capsule 908 and portion 911 of the thread 910 are released to fall to the back of the patient's tongue. The slider mechanism allows the bundled portion 911 to be released without twisting or straining the bundled thread, thereby introducing a twist to the thread 910 that could induce tangling. The patient can then swallow the capsule 908 along with at least a portion of the bundled portion 911.

[0082] Once capsule 908 is swallowed, the capsule at the end of the thread 910 moves down the esophagus. Capsule 908 may travel all the way to the patient's stomach. The operator holds capsule 908 by the thread 910 attached to applicator device 900a. The operator or the patient holds applicator device 900a stably, for example, by holding applicator device 900a against the patient's cheek.

[0083] After a certain period (typically several minutes), the capsule wall dissolves or opens, releasing the sponge. The sponge is then withdrawn from the esophagus by retracting the applicator device 900a to pull the thread 910 out of the patient. As the sponge is withdrawn from the esophagus, it collects a cell sample from the esophageal wall, as understood in the art. The operator continues to withdraw the sponge from the esophagus through the patient's mouth. The TTF3 test can then be performed on the cells collected by the sponge in the conventional manner. Before being sent for testing, the sponge may be detached from the rest of the device 900, for example, by cutting or uncoupling the retrieved thread 910.

[0084] While certain embodiments are described above, these embodiments are presented as examples only, and it will be understood that various omissions, substitutions, modifications, or additions may be made without departing from the scope of the invention as defined by the following claims.

Claims

1. A swallowable device for collecting cells, A swallowable capsule, A retrieval thread comprising: a retrieval thread whose proximal end is connected to an applicator device, and a portion of the thread is bundled together with the swallowable capsule, with the distal end of the thread connected to the swallowable capsule; A swallowable device for collecting cells, wherein, in the bundled state, the portion comprises multiple windings around one or more winding axes, and the direction of the windings around the one or more winding axes alternates between each successive winding.

2. A swallowable device for collecting cells according to claim 1, wherein the number of turns wound in a first direction is no more than one turn of turns wound in the opposite second direction.

3. A swallowable device for collecting cells according to claim 1 or 2, wherein each winding is wrapped over an angle of less than 180 degrees such that the portion includes a concertina configuration.

4. A swallowable device for collecting cells according to claim 1 or 2, wherein each winding is wrapped over an angle of 180 to 360 degrees such that the portion includes a figure-eight configuration.

5. The swallowable device for collecting cells according to any one of claims 1 to 4, wherein the one or more winding axes are a plurality of winding axes oriented parallel to each other.

6. A swallowable device for collecting cells, A swallowable capsule, A recovery thread comprising: a recovery thread connected to the swallowable capsule at its distal end, with the distal end of the thread connected to a packaging device; and a portion of the thread bundled together with the swallowable capsule. A swallowable device for collecting cells, wherein the aforementioned portion is wrapped around the bundled state in an over-under configuration.

7. A swallowable device for collecting cells, A swallowable capsule, A retrieval thread comprising: a retrieval thread connected to the swallowable capsule at its distal end, with the distal end of the thread connected to an applicator device; and a portion of the thread bundled together with the swallowable capsule. A swallowable device for collecting cells, wherein the portion is wound in a bundled state such that there is no net twist around the thread from the distal end of the portion to the proximal end of the portion.

8. A swallowable device for collecting cells, A swallowable capsule filled with at least partially weighted material, A swallowable device for collecting cells, comprising: a retrieval thread configured such that its distal end is connected to an applicator device, the retrieval thread being connected to a swallowable capsule at its distal end; and a portion of the thread being bundled together with the swallowable capsule.

9. The device for collecting cells according to claim 8, wherein the weighting material comprises polyethylene glycol.

10. A device for collecting cells according to any one of the prior claims, wherein the capsule contains an abrasive material, preferably a sponge material, for collecting cells.

11. A device for collecting cells according to any one of the prior claims, wherein, in the bundled state, the portion is positioned along the thread proximal to the distal end of the thread.

12. A device for collecting cells according to any one of the prior claims, wherein the portion of the retrieved thread has a length of at least 450 mm.

13. A packaging device for administering a swallowable device for collecting cells to a patient, comprising: a swallowable device for collecting cells according to any prior claim; and an applicator device for direct administration to the patient, connected to the proximal end of the retrieval thread and configured to releasably house the device for collecting cells and a portion of the retrieval thread.

14. A method for administering a swallowable device for collecting cells described in any of the prior claims, The steps include inserting the bundle and capsule into the patient's mouth, The steps include: holding the distal end of the retrieved thread while having the patient swallow the capsule and bundle; The steps include collecting a cell sample from the internal region of the patient using the swallowable capsule, A method comprising the step of retrieving the swallowable capsule by pulling the distal end of the retrieval thread out of the patient's mouth.

15. A method for manufacturing a swallowable device for collecting cells, The steps include: attaching a swallowable cell capsule to the distal end of the retrieval thread, A method comprising the steps of winding multiple turns around one or more winding axes, and bundling a portion of the recovered yarn by alternating the direction of winding around the winding axis in each consecutive turn.

16. The method according to claim 15, wherein the aforementioned portion is bundled using a winding device.

17. The method according to claim 16, wherein the winding device comprises a pair of winding posts projecting parallel to the surface of the winding device, the posts each comprising a pair of winding posts that define a winding axis, and the portion is bundled by winding a figure-eight pattern around the winding posts.

18. The aforementioned winding device, A pair of opposing trap regions, wherein the width of each trap region provides interference engagement with the retrieval thread, The trap region is separated by a gap, The method according to claim 16, wherein the portion is bundled by winding the retrieved thread with a concertina pattern that crosses the gap and passes through the trap area.

19. The method according to any one of claims 16 to 18, wherein the winding device comprises a capsule holder for positioning the swallowable capsule during winding.

20. A method for manufacturing a packaging device for administering a swallowable device for collecting cells, The steps include: attaching a swallowable cell capsule to the distal end of the retrieval thread, The steps include bundling a portion of the retrieved yarn by winding multiple loops around the winding axis in an over-under pattern, The steps include storing the capsule and a portion of the retrieved thread inside the applicator device, A method comprising the step of connecting the proximal end of the retrieved thread to the applicator device.

21. The aforementioned portion is bundled using a winding device, and the winding device is The aforementioned winding axis is defined, and the winding surface tapers from a wide end to a narrow end, The winding surface is provided with a capsule holder proximal to the narrow end, The method according to claim 20, wherein the portion is bundled by winding the retrieved yarn around the winding surface in an over-under pattern.

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