CN110997053B

CN110997053B - Systems, methods, and devices for fallopian tube diagnosis

Info

Publication number: CN110997053B
Application number: CN201880052679.5A
Authority: CN
Inventors: 杰西·马加纳; 戴维·W·斯诺; 阿伦·L·布拉德利; 克里斯蒂娜·克里斯特曼-斯基勒; 瑟柏海·萨尔纳
Original assignee: Nvision Medical Corp
Current assignee: Nvision Medical Corp
Priority date: 2017-08-17
Filing date: 2018-08-16
Publication date: 2021-12-17
Anticipated expiration: 2038-08-16
Also published as: AU2018319532A1; AU2018319532B2; JP2020530364A; CN110997053A; CN114391887A; CA3070679A1; WO2019040094A1; CN114391887B; EP3668584A1; JP7093404B2

Abstract

The present disclosure relates generally to devices, systems, and methods for fallopian tube diagnosis. In some embodiments, the tube may have a distal end, and the balloon may be coupled to the distal end of the tube. The bladder may be disposed in the tube in a first everted position and may be movable to a second everted position. The balloon may extend a distance distal to the distal end of the tube such that a surface of the balloon may be in contact with an inner surface of the fallopian tube. The push wire may have a distal end coupled to the second end of the balloon. The bladder may be moved from the first everted position to the second everted position by actuating the push wire. The surface of the balloon may include a plurality of surface features for collecting a tissue sample of the inner surface of the fallopian tube.

Description

Systems, methods, and devices for fallopian tube diagnosis

Cross Reference to Related Applications

The present application is a partial continuation application of U.S. patent application Ser. No. 15/053,568 entitled "Methods and Devices for Fallopia Tube Diagnostics" filed on 25.2.2016 and claiming priority, which is a partial continuation application of U.S. patent application Ser. No. 14/764,710 entitled "Methods and Devices for Fallopia Tube Diagnostics" filed on 30.7.2015, a national phase application of International patent application Ser. No. PCT/US2014/014472 filed on 3.2.2014, a provisional patent application Ser. No. 61/873,753 filed on 4.9.9.2013, entitled "Methods for Fallopia Tube Diagnostics" and a provisional patent application Ser. No. 3.3.3. 61/759,783 filed on 2013, a provisional patent application Ser. No. 3.4.3, a provisional patent application No. 61/873,753 filed on 3.4.9.3.4.e, and a provisional patent application Ser. No. 3.1.3.3.3.g. is filed for Fallopia Tube Diagnostics, the entire disclosures of these applications are expressly incorporated herein by reference.

This application is a non-provisional application entitled U.S. provisional application serial No. 62/546,791 entitled "Devices for Fallopian Tube Diagnostics" filed on 8/17 2017 and U.S. provisional application serial No. 62/660,512 entitled "Methods and Devices for Fallopian Tube Diagnostics" filed on 4/20 2018, the entire disclosures of which are expressly incorporated herein by reference, and the priority of which is claimed.

Technical Field

The present disclosure relates generally to fallopian tube diagnostics, and more particularly to systems, devices, and methods that address anatomical difficulties (for tissue sample collection) associated with navigation through body lumens, including fallopian tubes.

Background

Ovarian cancer is a significant disease in women, and in the united states, 1 of 72 women may be diagnosed with the disease throughout her lifetime. In 2012, more than 22,000 women in the united states were diagnosed with ovarian cancer. Lack of an effective screening test may make early detection of ovarian cancer difficult, such that diagnosis of ovarian cancer is not possible until the disease has progressed to an advanced stage, thereby limiting treatment options.

Screening for ovarian cancer may typically include surgery to obtain a sample of cells for diagnosis. For example, since the ovary is inside the abdomen, laparoscopic or open surgery (laparotomy) may be performed to access the ovary. Any surgical procedure increases the risk to the patient, including but not limited to the occurrence of adverse reactions and/or the need for substantial recovery time. Furthermore, ovarian biopsy may expose the patient to additional risk of potentially spreading diseased (e.g., cancerous) cells.

Accordingly, there is a need for devices and methods that allow for obtaining samples from fallopian tubes for the assessment of ovarian cancer in a less invasive and controlled manner, and in particular without the need for skin incisions. There is a further need for using a catheter to obtain a representative cell sample from the fallopian tube for screening for early stage cancer.

In view of these and other considerations, improvements of the present disclosure are useful.

Disclosure of Invention

This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to necessarily identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.

According to an exemplary embodiment of the present disclosure, a device for fallopian tube diagnosis may include a tube having a distal end and a balloon having a first end coupled to the distal end of the tube. The balloon may be disposed in the tube in a first everted position, may be moved to a second everted position, and may extend a distance distal to the distal end of the tube such that a surface of the balloon may be in contact with an inner surface of the fallopian tube. The push wire may have a distal end coupled to the second end of the balloon. The bladder may be moved from the first everted position to the second everted position by actuating the push wire. The surface of the balloon may include a plurality of surface features for collection, retention, or both of tissue samples of the interior surface of the fallopian tube.

In various of the foregoing and other embodiments of the present disclosure, the surface features may include a plurality of folds formed in the surface of the balloon, and may have at least one of a plurality of edges, micro-ridges, or overlapping materials, or a combination thereof. A plurality of wrinkles may be formed in the surface of the capsule. A plurality of folds in the balloon surface may be formed in the balloon surface and may be configured to retain at least a portion of the tissue sample after contacting an inner surface of the fallopian tube. Surface features may be etched into the surface of the capsule. A portion of the surface of the capsule may be embossed to form a plurality of peaks and valleys. The plurality of surface features may improve adhesion of the tissue sample to the balloon surface compared to a balloon surface without the surface features. The balloon may be inflatable for moving the balloon from a first, inverted position to a second, inverted position. The filament may be attached to the push wire, the filament may be disposed within the balloon in a first everted position, and the filament may extend from the balloon in a second everted position.

According to an example embodiment of the present disclosure, a system for collecting a tissue sample in a body lumen may include a tube having a distal end and a balloon having a first end coupled to the distal end of the tube and a second end coupled to the distal end of a push wire. The bladder may be positioned in a first everted state. The push wire may be configured to travel to evert the balloon to a second everted state such that the balloon extends out of the distal end of the tube. The surface of the balloon may be configured in a second everted state to contact an inner surface of the body lumen for transferring the tissue sample to the balloon surface. The balloon surface may include a plurality of surface features for collection, retention, or both of tissue samples.

In various of the foregoing and other embodiments of the present disclosure, the surface features may include a plurality of folds formed in the balloon surface, the folds having at least one of a plurality of edges, micro-ridges, or overlapping materials, or combinations thereof. A plurality of wrinkles may be formed in the surface of the capsule. The plurality of folds in the balloon surface may be configured to retain at least a portion of the tissue sample after contacting an inner surface of the body lumen. Surface features may be etched on the surface of the capsule. The plurality of surface features may improve adhesion of the tissue sample to the balloon surface compared to a balloon surface without the surface features.

According to an example embodiment of the present disclosure, a method for collecting a tissue sample in a body lumen may include providing a tube having a distal end and a balloon having a first end coupled to the distal end of the tube and a second end coupled to the distal end of a push wire. The bladder may be positioned in a first everted state. The push wire may be advanced to evert the balloon to a second everted state such that the balloon extends out of the distal end of the tube. The balloon surface may contact an inner surface of the body lumen in the second everted state. The balloon surface may include a plurality of surface features for collection, retention, or both of tissue samples.

In various of the foregoing and other embodiments of the present disclosure, the surface features may include a plurality of folds formed in the surface of the balloon, and may have at least one of a plurality of edges, micro-ridges, or overlapping materials, or a combination thereof. A plurality of wrinkles may be formed in the surface of the capsule. The plurality of folds in the balloon surface may be configured to retain at least a portion of the tissue sample after contacting an inner surface of the body lumen. The plurality of surface features may improve adhesion of the tissue sample to the balloon surface compared to a balloon surface without the surface features.

According to an exemplary embodiment of the present disclosure, a device for fallopian tube diagnosis may include a tube having a distal end and a balloon having a first end coupled to the distal end of the tube. The balloon may be disposed in the tube in a first everted position, may be movable to a second everted position, and may extend a distance distally of the tube. The extension portion may have a proximal end coupled to the second end of the balloon. The extension portion may be disposed within the bladder in a first everted position and may extend from the second end of the bladder in a second everted position.

In various of the foregoing and other embodiments of the present disclosure, the extension portion may be any one of a filament, suture, or string, or a combination thereof. At least a portion of the filament, suture or string, or a combination thereof, may be braided. The extension may be formed from one or more filaments having a color. The color of the one or more filaments of the extension portion may provide a contrasting visual effect. The extension portion may include one or more knots or markings for one or both of visual feedback and tactile feedback. The extension portion may be a braided filament configured to collect and retain a tissue sample in response to extending from the balloon in the second everted position. The push wire may have a distal end coupled to the second end of the balloon and a proximal end of the extension portion. The balloon and extension may be moved from the first everted position to the second everted position by actuating the push wire.

According to an example embodiment of the present disclosure, a system for collecting a tissue sample in a body lumen may include a tube having a distal end, and a balloon may have a first end and a second end coupled to the distal end of the tube. The extension portion may be attached to the second end of the bladder. The bladder and the extension may be positioned in a first inverted state. The balloon and the extension portion may be configured to advance to a second everted state such that the balloon and the extension portion may extend out of the distal end of the tube. The extension portion may be disposed within the balloon in a first everted position and may extend from the balloon into the body lumen in a second everted position.

In various of the foregoing and other embodiments of the present disclosure, the extension portion may be any one of a filament, suture, or string, or a combination thereof. At least a portion of the filament, suture or string, or a combination thereof, may be braided. The extension may be formed from one or more filaments having a color. The color of the one or more filaments of the extension portion may provide a contrasting visual effect. The extension portion may include one or more knots or markings for one or both of visual feedback and tactile feedback. The extension portion may be a braided filament configured to collect and retain a tissue sample in response to extending from the balloon in the second everted position into a body lumen. The push wire may have a distal end coupled to the second end of the balloon and a proximal end of the extension portion. The balloon and extension may be moved from the first everted position to the second everted position by actuating the push wire.

According to an example embodiment of the present disclosure, a method for collecting a tissue sample in a body lumen may include providing a tube having a distal end and a balloon having a first end and a second end coupled to the distal end of the tube. The extension portion may be attached to the second end of the bladder. The bladder and the extension portion may be positioned in a first everted state. The balloon may be advanced to a second everted state such that the balloon and the extension may extend out of the distal end of the tube. The extension portion may be disposed within the balloon in a first everted position and may extend from the balloon into the body lumen in a second everted position.

In various of the foregoing and other embodiments of the present disclosure, the tissue sample may be collected by an extension portion that may extend from the balloon into the body lumen at the second everted position. The extension may be any one of a braided filament, a braided suture or a braided string, or a combination thereof. The extension may be formed from one or more filaments having a color. The color of the one or more filaments of the extension portion may provide a contrasting visual effect. The extension portion may be a braided filament and may be configured to collect and retain a tissue sample in response to extending from the balloon in the second everted position into a body lumen. The push wire may have a distal end coupled to the second end of the balloon and a proximal end of the extension portion, and may be actuated to move the balloon and the extension portion from the first everted position to the second everted position.

According to exemplary embodiments of the present disclosure, devices, systems, and methods for fallopian tube diagnosis may include a tube having a distal end and a proximal end, and a sheath disposed coaxially with the tube. The balloon may have a first end and a second end coupled to the distal end of the tube, and the sheath may extend over the balloon. The sheath may provide column strength to the balloon when the balloon is moved from the first everted position to the second everted position into the fallopian tube. The sheath may minimize balloon collapse as the balloon everts into the fallopian tube. The sheath may protect the everted balloon or the extension, or both, after removal of the collection of cells from the patient. The sheath knob may connect the sheath to the tube. The sheath knob may be configured to lock the sheath to the tube to minimize relative movement. The sheath knob may be configured to unlock the sheath from the tube for adjustment of the sheath relative to the balloon and the tube.

According to exemplary embodiments of the present disclosure, devices, systems, and methods for fallopian tube diagnosis may include one or more markers for visualization. The first indicia may be disposed on the tube and may indicate a position of the tube relative to the sheath or sheath knob. The first indicia may indicate a positioning of the sheath relative to the tube as a preparatory step to cover at least a portion of the balloon in the second everted position. The first indicia may indicate the positioning of the sheath relative to the tube for initial advancement of the balloon into the fallopian tube. In response to at least a portion of the balloon being in the second everted position, the sheath may be moved in a proximal direction to expose at least a portion of the balloon. The second indicia may be disposed on the tube and may indicate a position of the tube relative to the sheath or sheath knob. The second marker may indicate the positioning of the sheath relative to the tube as a retraction marker for visualizing the sheath to cover the everted balloon and/or extension after cell collection to protect the collected cells. The second marker may be disposed at a proximal portion of the tube. The third marker may be disposed on the tube and may be located at a distal end of the tube relative to a connection point of the balloon and the tube. The third indicia may visually indicate the end of the fallopian tube to confirm the extension or positioning of the balloon and/or extension in the fallopian tube. The one or more indicia may be formed as score lines, a coating substance or a strip of material, or a combination thereof. The one or more markers may improve or standardize the location and extension of the balloon into the fallopian tube. A seal may be disposed about the push wire and positioned relative to the pressurization chamber 116. The push wire may be movable relative to the seal to travel through the tube to actuate the balloon between a first everted position and a second everted position. In response to a leak forming between the push wire and the conical seal, the seal may be adjusted to maintain pressure for moving the bladder between the first everted position and the second everted position.

According to exemplary embodiments of the present disclosure, devices, systems, and methods for fallopian tube diagnostics can include that at least a portion of the sheath can be translucent, transparent, or otherwise see-through. At least a portion of the tube may be translucent, transparent, or otherwise see-through. At least a portion of the capsule may be translucent, transparent, or otherwise see-through. The tube may include a transparent portion and an opaque portion. An opaque portion may be provided at the proximal end of the tube. The transparent portion of the tube may be more flexible than the opaque portion of the tube. The transparent portion of the tube may extend along the inner diameter and length of the opaque portion of the tube. The extension portion may be connected to the bladder and may be disposed within the bladder in a first everted position and may extend from the bladder in a second everted position. When in the first everted position, the extension portion is visible through the balloon, tube and sheath. The balloon may be inflated by an opaque, or visible or detectable fluid for visualization, to move from the first everted position to the second everted position.

According to an exemplary embodiment of the present disclosure, a device, system, and method for fallopian tube diagnostics can include a handle including a gear mechanism for actuating a push wire. The gear mechanism may comprise a plurality of gears and may be operated by the drive wheel. The gear mechanism may comprise a reduction ratio for additional control of the movement of the balloon. The drive wheel and gear mechanism may provide uniform movement of the bladder during movement between the first everted position and the second everted position. In response to extending the push wire to its proximal end, the handle may include a limiting mechanism for providing audible or tactile feedback to the user. The pawl may be engageable with one or more gears for stopping rotation of the gears. The pawl may be spring biased towards the rack and pinion. The pawl may engage and slide over the teeth of the rack and pinion to provide audible or tactile feedback to the user. The teeth may have a steeper slope on the first side and a more moderate slope on the second side.

Drawings

Non-limiting embodiments of the present disclosure are described by way of example with reference to the accompanying drawings, which are schematic and are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated is typically represented by a single numeral. For purposes of clarity, not every component may be labeled in every drawing, nor may every component of each embodiment be shown (where illustration is not necessary) to allow those of ordinary skill in the art to understand the disclosure. In the drawings:

FIG. 1 shows a cross-sectional view of a fallopian tube connecting the uterus to the ovary, having a uterotubal junction (UTJ);

FIGS. 2A-2D illustrate an exemplary embodiment of sequential insertion of a catheter into a fallopian tube according to the present disclosure;

fig. 3 shows a schematic view of a hysteroscope for deploying an exemplary embodiment of a catheter according to the present disclosure;

fig. 4 illustrates an exemplary embodiment of a proximal introducer catheter in accordance with the present disclosure;

figure 5A shows a cross-sectional view of an exemplary embodiment of an everting sleeve (with a distal elastic balloon tip, and in a contracted state) according to the present disclosure;

figure 5B shows a cross-sectional view of an everting sleeve (having the distal elastic balloon tip of figure 5A and in an inflated state) according to the present disclosure;

figure 6A shows a cross-sectional view of an exemplary embodiment of an everting balloon (with an externally configured sleeve, and in a deflated state) according to the present disclosure;

figure 6B shows a cross-sectional view of an everting balloon (with the outer configuration sleeve of figure 6A, and in an inflated state) according to the present disclosure;

figure 6C illustrates an exemplary embodiment of inflation of an everting balloon having the outer configuration sleeve of figures 6A-6B;

figure 7A shows a cross-sectional view of an exemplary embodiment of an everting sleeve and an elastic balloon (with a non-elastic delivery balloon, and in a deflated state) according to the present disclosure;

figure 7B shows a cross-sectional view of an everting sleeve and an elastic balloon (with the inelastic delivery balloon of figure 7A, and in an inflated state) according to the present disclosure;

fig. 7C shows an exemplary embodiment of the inflation of an everted sleeve and an elastic balloon with the inelastic delivery balloon of fig. 7A-7B;

figure 8A illustrates a cross-sectional view of an exemplary embodiment of an elastic balloon and everting sleeve with an irrigation lumen in a deflated state according to the present disclosure;

FIG. 8B shows a cross-sectional view of an elastic balloon and everting sleeve with the irrigation lumen of FIG. 8A in an inflated state according to the present disclosure;

figure 9A illustrates a cross-sectional view of an exemplary embodiment of an everting balloon catheter in a collapsed state according to the present disclosure;

figure 9B illustrates a cross-sectional view of the everting balloon catheter of figure 9A in an inflated state according to the present disclosure;

FIG. 9C is an exemplary embodiment of a helical filament according to the present disclosure;

figure 10A illustrates a cross-sectional view of an exemplary embodiment of an everting balloon catheter in a deflated state according to the present disclosure;

figure 10B illustrates a cross-sectional view of the everting balloon catheter of figure 10A in an inflated state according to the present disclosure;

figure 11A illustrates a cross-sectional view of an exemplary embodiment of an everting balloon catheter in a deflated state according to the present disclosure;

figure 11B illustrates a cross-sectional view of the everting balloon catheter of figure 11A in an inflated state according to the present disclosure;

figures 11C-11D show cross-sectional views of an exemplary embodiment of an everting balloon catheter according to the present disclosure;

figures 11E-11F show cross-sectional views of an exemplary embodiment of an everting balloon catheter according to the present disclosure;

figure 12A illustrates a cross-sectional view of another exemplary embodiment of an everting balloon catheter in a deflated state according to the present disclosure;

figure 12B illustrates a cross-sectional view of the everting balloon catheter of figure 12B in an inflated state according to the present disclosure;

figure 13A illustrates a cross-sectional view of an exemplary embodiment of an everting balloon catheter in a deflated state according to the present disclosure;

figure 13B illustrates a cross-sectional view of the everting balloon catheter of figure 13A in an inflated state according to the present disclosure;

figure 14A illustrates a cross-sectional view of another exemplary embodiment of an everting balloon catheter in a deflated state according to the present disclosure;

figure 14B illustrates a cross-sectional view of the everting balloon catheter of figure 14A in an inflated state according to the present disclosure;

figure 15A illustrates a cross-sectional view of an exemplary embodiment of an everting balloon helical cannula in a deflated state according to the present disclosure;

figure 15B illustrates the everting balloon helical cannula of figure 15A in an inflated state according to the present disclosure;

figure 16A illustrates a cross-sectional view of an exemplary embodiment of an everted distal arcuate balloon cannula in a deflated state according to the present disclosure;

figure 16B illustrates the everted distal arc balloon cannula of figure 16A in an inflated state according to the present disclosure;

figure 17A illustrates a cross-sectional view of another exemplary embodiment of an everting balloon catheter in a deflated state according to the present disclosure;

figure 17B illustrates the everting balloon catheter of figure 17A in an inflated state according to the present disclosure;

FIG. 18 illustrates an exemplary embodiment of an extension element according to the present disclosure;

FIG. 19 shows an exemplary embodiment of an extension portion in a retracted state after cell collection according to the present disclosure;

FIG. 20 shows the isolated extension portion of FIG. 19 in a deployed state according to the present disclosure;

figure 21A illustrates a side cross-sectional view of an exemplary embodiment of a spherical tip eversion balloon catheter prior to balloon deployment according to the present disclosure;

figure 21B illustrates a side cross-sectional view of an exemplary embodiment of the spherical end everting balloon catheter of figure 21A in a deployed state according to the present disclosure;

figures 22A-22C illustrate an exemplary embodiment of an everting balloon exiting from a catheter according to the present disclosure;

figure 23A illustrates a side cross-sectional view of an exemplary embodiment of a balloon-tip catheter according to the present disclosure;

figure 23B illustrates the balloon-tip catheter of figure 23A according to the present disclosure;

figure 23C illustrates the balloon-tip catheter of figure 23A according to the present disclosure;

fig. 24 shows a side cross-sectional view of an exemplary embodiment of a balloon-tipped catheter according to the present disclosure;

fig. 25 shows a side view of an exemplary embodiment of a balloon-tipped catheter according to the present disclosure;

FIG. 26A shows a cross-sectional view of an exemplary embodiment of a handle of the catheter of FIG. 25, according to the present disclosure;

FIG. 26B is a detail view illustrating an exemplary embodiment of the gear system in the handle portion of the catheter of FIG. 26A according to the present disclosure;

FIG. 26C illustrates a perspective view of an exemplary embodiment of a linear rack and ratchet assembly according to the present disclosure;

FIG. 26D illustrates a side view of an exemplary embodiment of a drop key snap of the linear rack and ratchet assembly of FIG. 26C according to the present disclosure;

FIG. 26E illustrates a side view of an exemplary embodiment of a gear jam according to the present disclosure;

fig. 27 shows a side cross-sectional view of an exemplary embodiment of a balloon-tip catheter according to the present disclosure;

fig. 28 shows a side cross-sectional view of an exemplary embodiment of a balloon-tip catheter according to the present disclosure;

fig. 29A-29C are a series of side perspective views of an exemplary embodiment of a steerable balloon tip using a guidewire according to the present disclosure;

fig. 30 shows a side perspective view of an exemplary embodiment of a balloon catheter and a guiding balloon tip according to the present disclosure;

fig. 31 shows a side perspective view of an exemplary embodiment of a balloon catheter with a flexible guidewire according to the present disclosure;

fig. 32 shows an exemplary embodiment of a balloon prior to inversion into a catheter according to the present disclosure;

fig. 33 shows a side cross-sectional view of an exemplary embodiment of a balloon-tip catheter having the balloon of fig. 32 and a sheath inverted in accordance with the present disclosure;

FIG. 34A shows a side perspective view of an exemplary embodiment of a string filament having a series of printed indicia in accordance with the present disclosure;

FIG. 34B shows a side perspective view of an exemplary embodiment of a string filament having a series of knots as a marker in accordance with the present disclosure;

figure 35 shows eversion of an exemplary embodiment of a bladder according to the present disclosure;

figure 36A illustrates a cross-sectional view of an exemplary embodiment of a bladder according to the present disclosure; and

fig. 36B illustrates a cross-sectional view of an exemplary embodiment of a bladder according to the present disclosure.

Detailed Description

The present disclosure is not limited to the specific embodiments described herein. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope beyond the appended claims. Unless defined otherwise, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

Where a range of values is provided, it is understood that intermediate values between the upper and lower limit of the range up to one tenth of the unit of the lower limit are also specifically disclosed, unless the context clearly dictates otherwise. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range (where either, neither or both limits are included in the smaller ranges) is also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and/or "comprising," or "includes" and/or "including," when used herein, specify the presence of stated features, regions, steps, elements, and/or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and/or groups thereof.

As noted above, challenges in effectively detecting early stage cancer (e.g., ovarian cancer) in women may include taking biopsy samples without surgery. Anatomically, the ovary is very close to the fimbria in the region of the distal opening or neck of the fallopian tube. Ova released from the ovaries can be collected by the fimbria and transported to the uterus via the fallopian tubes. For ovarian cancer, cells may be deposited in the fallopian tubes and may eventually migrate into the uterus. Ovarian malignancies can be detected from cell samples taken from the uterus; however, the incidence of migration of ovarian cancer cells into the uterus may be too low to enable uterine sampling as a reliable diagnostic test for ovarian malignancy.

More cancer cells may migrate to or originate in the fallopian tubes, which may be concentrated in the distal portion of the fallopian tubes near the distal neck. The ability to detect cells in the fallopian tubes for malignancy may be of clinical value for the early detection and treatment of this cancer. It should be appreciated that an early detection screen can be performed that detects migrating cancer cells.

The fallopian tubes are extremely fragile and easily perforated during the medical procedure. Thus, it may be difficult to safely introduce a diagnostic device into a fallopian tube with known devices. Referring now to fig. 1, a patient's fallopian tubes 1 may extend from a proximal cervical orifice 3 (connected at a uterotubal junction (UTJ) 2) near the uterus, to a distal cervical orifice 5 and connect to the ovaries 6. Perforation may occur at UTJ 2, which is a constriction that occurs distal to the proximal neck 3 (e.g., opening) of the fallopian tube. For example, in some patients, UTJ 2 may be about 1cm away from the proximal neck finish 3. In some patients, the body lumen size at the constriction can be as small as about 0.3mm or 0.5mm, while the body lumen size of the fallopian tube adjacent to the UTJ can be about 1 mm.

According to exemplary embodiments, the systems and methods of the present disclosure can engage the inner wall of a fallopian tube, and can remove cells from the fallopian tube for diagnostic purposes. Devices and methods may be provided for collecting such cells in a less invasive surgical procedure, which in some embodiments occurs without a skin incision. Although the description relates to sample collection and diagnosis of the fallopian tubes, it should be understood that the systems and methods of sample collection and diagnosis may be applicable to any other body lumens, tubes, and ducts, including but not limited to the bile duct, hepatic duct, cystic duct, pancreatic duct, lymphatic duct, and circulatory vessels according to the present disclosure.

Embodiments of exemplary catheters for fallopian tube diagnostics can be provided for performing less invasive surgical procedures, including any of the following: (1) accessing a proximal neck opening of a fallopian tube via an intrauterine route; (2) advancing an introducer catheter to cannulate and form a fluid-tight seal with the proximal neck; (3) using a second catheter within the introducer catheter to advance the length of the fallopian tube and out into the abdominal cavity; (4) as the second catheter is retracted, the balloon at the end of the second catheter inflates until it seals the distal neck of the fallopian tube (retraction of the second catheter may result in contact with the luminal surface of the fallopian tube to remove cells for improved sampling); and/or (5) flushing the fallopian tubes and recovering the flushing fluid for cytological or cellular analysis.

Exemplary embodiments of a catheter for fallopian tube diagnosis for minimally invasive surgery may include any of the following: (1) accessing a proximal neck opening of a fallopian tube via an intrauterine route; (2) advancing an introducer catheter to cannulate the proximal neck; (3) a second catheter within the introducer catheter is used to travel into the fallopian tube. An inflation balloon at the end of the second catheter may be advanced through a proximal portion of the fallopian tube and may be everted further into the fallopian tube; (4) the balloon may contact the luminal surface of the fallopian tube and may remove cells for sampling; and/or (5) the capsule may be removed and inserted into a vial for cell collection and subsequent processing.

An exemplary catheter embodiment may be configured for insertion into a fallopian tube (see fig. 1). The fallopian tubes have a curvature (e.g., have a tortuous path), and the soft tissue of the tube may be collapsible, thereby resulting in multiple constrictions when attempting to pass through. As mentioned above, this may be particularly true at the uterotubal junction (UTJ), which may be muscular and therefore more easily perforated by insertion of a medical device. In some patients, the UTJ may also exhibit a downward bend, where the lumen size at the constriction may be as small as about 0.3mm or 0.5mm, while the body lumen size of the fallopian tube adjacent to the UTJ may be about 1 mm.

In at least one embodiment of the present disclosure, an elongate balloon that is initially inverted into a catheter lumen may be deployable. The balloon may be partially everted to access the proximal end of the fallopian tube, e.g., UTJ, thereby cannulating the proximal neck. When the balloon is pressurized from inside the catheter, the balloon may evert such that the everting deployment mechanism creates a path through the fallopian tube, regardless of the tortuosity or constriction of the fallopian tube. In some embodiments, the balloon may be everted by advancement of a push wire, which may coincide with pressurization. The balloon may be substantially inelastic for a majority of its length such that the balloon does not substantially inflate and dilate the fallopian tube when everted. Balloon inflation may rupture or otherwise damage or injure the fallopian tubes. However, exemplary embodiments may also incorporate a resilient distal balloon end that is expandable to seal the distal neck when the distal balloon is retracted. In some embodiments, the device may have a balloon that is sufficiently rigid to intubate the fallopian tube and sufficiently flexible to navigate a tortuous path through the fallopian tube, thereby minimizing potential damage or injury. In some embodiments, the device may include a support element for cannulating the fallopian tube such that the balloon does not collapse at the proximal neck opening.

Exemplary embodiments of the systems and methods of the present disclosure may include positioning and deployment of the distal end of a catheter. In some embodiments, the distal end of the catheter may be delivered to the proximal end of the fallopian tube through a hysteroscope. In some embodiments, the hysteroscope may be an exemplary hysteroscope (e.g., fig. 3). Regardless of the mode of deployment, the retrieval portion of the catheter may be extendable to contact the inner wall of the fallopian tube. It has been surprisingly found that the action of extending a portion of the catheter can remove sufficient cell and/or tissue samples from the fallopian tube wall for histological and/or cytological evaluation. For example, at least a portion of the length of the balloon may contact the fallopian tube for sample collection. In some embodiments, a majority of the length of the balloon may be substantially inelastic such that the balloon, when everted, does not substantially inflate and dilate a body lumen (e.g., a fallopian tube). In some embodiments, the balloon may be sized such that the body lumen does not expand or dilate as the balloon everts. As mentioned above, balloon inflation may rupture or damage a body lumen of a subject. According to some embodiments, and as discussed above with respect to the exemplary balloon catheter, the balloon may only extend longitudinally into a body lumen by everting from the catheter, such that the balloon does not substantially inflate and dilate the lumen when everted or extended into the body lumen (e.g., a fallopian tube). In some embodiments, the balloon may extend longitudinally into the body lumen, wherein the inflated balloon may have a diameter up to about 10-15% larger than the diameter of the fallopian tube. Radial expansion of the balloon may be limited or controlled by the substantial length of the balloon being substantially inelastic. It will be appreciated that the portion of the balloon not intended for insertion into the luminal structure may be elastic and therefore may be inflatable and compliant in diameter rather than substantially inelastic. Such hybrid capsules may be well suited in some embodiments when a seal with a UTJ is desired. Exemplary conditions requiring sealing may include flushing the lumen, filling the lumen with an imaging contrast agent, diagnosing an occlusion, and/or localized contact with a therapeutic agent (such as a chemotherapeutic agent or an antibiotic).

It has also been surprisingly found that withdrawing the extended portion of the capsule can dislodge more cells. In some embodiments, the extension can be retracted prior to catheter removal to prevent the harvested tubal cells from spreading to the surrounding tissue. In some embodiments, a slidable sheath may be deployable to protect the collected sample. With the catheter removed, the extension portion can deposit at least a portion of the collected sample (e.g., luminal cells) via contact with a microscope slide or other diagnostic substrate for detection of abnormal cells (e.g., cancerous cells). In some embodiments, a stain may be released in the fallopian tube for identifying abnormal and potentially cancerous cells.

Referring now to fig. 2A-2D, the inverted non-elastic sleeve 12 and attached distal elastic balloon 14 may be inserted through an introduction catheter 10, which introduction catheter 10 may be in a working channel 22 of a surgical hysteroscope 20 (fig. 3) and used to cannulate the proximal neck orifice of the fallopian tube 1, as shown in fig. 2A. In fig. 2B, the balloon may be inflated to evert the sleeve 12 over the length of the fallopian tube 1 and expand the distal elastic balloon 14. In fig. 2C, after the inverted elastic sleeve 12 has fully advanced and the elastic balloon 14 has inflated, the balloon may be at least partially retracted proximally to seal the distal neck-finish 18 of the fallopian tube 1. Fig. 2D shows the introduction of saline for irrigation along the length of the fallopian tube 1 between the introducer catheter 10 and the everting sleeve 12. The retraction of the inflated elastomeric balloon 14 seals the opening of the distal neck. The flushing fluid is then collected to obtain a cell sample from substantially the entire length of the fallopian tube 1 for detection of cell analysis in ovarian cancer or other health conditions. In one embodiment, a stain may be present in the irrigation fluid introduced into the fallopian tube for identifying and/or distinguishing between abnormal and potentially cancerous cells. Illustrative examples of stains may include a fluorescence imaging agent attached to a modified type of folic acid that may be used as a homing device to find ovarian cancer cells to attach to. In some embodiments, the multispectral fluorescence camera may illuminate the detected cells, for example by a monitor visually identifying their locations. For the growth and division of ovarian cancer cells, the cells require large amounts of vitamins (folic acid). Specific receptors on the surface of cancer cells grab the vitamin and anything it attaches to and pull it inside.

The catheter 10 described above and in more detail below may be introduced into the uterus of a patient using a surgical hysteroscope 20, an example of which is shown in fig. 3. The surgical hysteroscope 20 may include one or more working channels. One channel may provide irrigation to enlarge the uterus and allow for endoscopic visualization, and one or more additional working channels 22 may allow for distal advancement of instruments and/or catheters to the hysteroscope. A proximal introducer catheter 10 (see, e.g., fig. 2A and 4) may be advanced through the working channel of the surgical hysteroscope 20 and may be used to cannulate the tubal proximal neck. The balloon 24 on the proximal introducer catheter 10 may be inflated to occlude the proximal neck (e.g., fig. 4), and an everted sleeve catheter may be advanced through the proximal introducer catheter 10 to the proximal portion of the fallopian tube. The sleeve/balloon element 14 may be fully everted and the inflated balloon tip may be pulled back to seal the distal neck. Irrigation fluid may be introduced through port 11 and withdrawn through irrigation port 11 on the proximal introducer catheter 10 to collect a sample. Irrigation fluid may also be introduced through the everted sleeve catheter and the proximal introducer catheter, and then aspirated out through one or both ports (11, 13) of the proximal introducer catheter.

In an embodiment of the catheter 10, the sleeve 12 of the everting sleeve catheter may be a flexible, elongated, substantially inelastic tube having an elastic balloon tip 14 attached to its distal end, see fig. 5A and 5B. The non-elastic tube 12 may have a plurality of ridges 15, these ridges 15 being arranged to extend along its length to the outside of the tube when the tube has been everted or extended/deployed, as shown in fig. 5B. As shown in fig. 5A, the ridges may extend inward when the tube is inverted prior to deployment. As the ridges extend outward, as shown in fig. 5B, the ridges may be exposed to the luminal surface of the fallopian tube when the sleeve is fully everted. These ridges may increase the ability of the sleeve to collect cells when the balloon is retracted, for example by additional surface area and/or frictional contact. In some embodiments, the outer surface of the everted inelastic balloon may be covered with fabric or otherwise textured, which may increase cell dislodgement and improve cell collection during balloon retraction, as described below.

Fig. 6A-6C show an exemplary embodiment of an everting sleeve catheter 10A that may protect the junction between the balloon 14A and the sleeve 17 of the everting sleeve catheter 10A during deployment 10A. The everting sleeve catheter 10A of fig. 6A-6C may include an elongate elastic balloon attachable to the distal tip of the everting sleeve catheter. A substantially inelastic sleeve 17 that is slightly shorter in length than the elastic balloon 14 may be attached to the elastic balloon 14 at the distal tip of the catheter and may be invertible such that in an undeployed state the inelastic sleeve 17 is positioned inside the elastic balloon 14. In response to eversion of the balloon/

sleeve combination

14A, 17, the inelastic sleeve 17 may be exposed from the double wall 19 of the catheter 10A such that a portion of the elastic balloon 14A in the extended position is inside the inelastic sleeve 17, e.g., the inelastic sleeve 17 is disposed outside the elastic balloon 14A and may constrain the elastic balloon 14A along its length, e.g., a majority of its length, to prevent the elastic balloon 14 from inflating and potentially rupturing the fallopian tube during advancement of the everted sleeve through the fallopian tube. When the balloon/sleeve is fully everted, the distal elastic balloon may expand to about 3 to 5 times the diameter of the sleeve for occluding the distal neck opening upon catheter retraction with concomitant retraction of the expanded balloon. In some embodiments, the catheter may contain a port 11 to allow irrigation to occur between the balloon and the non-elastic sleeve 17.

Fig. 7A-7C show an exemplary embodiment of an everting sleeve catheter 10b comprising a concentric double wall catheter and three layers of eversion attached to the distal catheter tip. An elongated nonelastomeric balloon 21 may be attached to the distal tip of the inner catheter 23, and the balloon 21 may be located within the inner catheter lumen 25. In some embodiments, the length of the elongated elastic balloon 14B may be equal to the length of the inelastic balloon 21, and the elongated elastic balloon 14B may be attached to the distal tip of the outer wall 27 of the catheter 10B. Bladder 14B may be disposed within a non-elastomeric bladder 21. A non-elastic sleeve 29 may be attached to the distal tip of the outer catheter wall 27, and in some embodiments, the length of the non-elastic sleeve 29 may be shorter than the elastic balloon 14B. Sleeve 29 may be disposed inside elastic balloon 14B in an undeployed state. Pressurization of the inner catheter 23 may evert the nonelastic balloon 21, which nonelastic balloon 21 may deliver the elastic balloon 14B and the outer nonelastic sleeve 29. After all three layers are fully everted, pressurization between the walls of the inner and outer catheters may inflate the elastic balloon 14B. The non-elastic sleeve 29 may constrain the elastic bladder 14B along a substantial portion of its length. The distal unconstrained tip 14T of the balloon may be expanded to form an occlusive element. This may be advantageous to reduce friction in the system during eversion. For example, the inelastic balloon 21 may deliver the elastic balloon 14B and the inelastic sleeve 29. The elastic bladder 14B does not undergo expansion until it is fully everted. In this way, the elastic balloon 14B may avoid frictional contact with the walls of the non-elastic sleeve 29 during eversion, which may be advantageous to facilitate deployment, for example, when working with small diameter catheters for crossing the fallopian tubes.

Fig. 8A-8B show an exemplary embodiment of an everted sleeve catheter 10C comprising a non-elastic sheath 29A with a small lumen 31 for irrigation, wherein the sheath 29A is connectable to a third port 11A for fluid irrigation and aspiration for obtaining a cytological sample. As noted above, in some embodiments, the irrigation fluid may contain a stain for identifying abnormal and potentially cancerous cells.

Another exemplary embodiment according to the present disclosure is shown in fig. 9A-9C and 10A-10B. An elongated balloon 32 including an extension 34 (e.g., an inflatable member) may be inverted into a lumen 36 of catheter 30, extension 34 being attachable to a distal end of balloon 32. In an inverted, e.g., undeployed, state, the extension 34 may be located within the elongate balloon 32. In some embodiments, extension 34 may be a helix of one or more turns of filament 38. The filaments forming the extensions 34 may be formed from a variety of materials, including, by way of example: monofilament polymer materials such as nylon or polypropylene, fluoropolymers, or polylactic acid; metals such as stainless steel titanium or platinum; or a superelastic metal, such as nitinol, or a combination thereof. In some embodiments, fiducial markers may be included on the filament and/or balloon and may be delivered to the fallopian tube (not shown) for subsequent return to the location of cell sampling. It will be appreciated that the extension portion may also have alternative configurations, such as an inflatable member. The extension 34, such as an expandable member, may contain a plurality of outwardly oriented bristles 40 formed of a polymer or metal (see fig. 18). In some embodiments, the extension portion 34 may be included as an elongated strand of material 38, the strand of material 38 being crimped, dispersed, or fanned out 42, crimped 44 to a predetermined shape (fig. 11A-11F or 14A-14B), or a combination thereof when released from being constrained within a catheter. In some embodiments, the extension 34, such as an expandable member, may be formed from a compressed polymer foam that self-expands when released into a wet environment (fig. 12A-12B). Upon pressurizing the catheter adjacent the proximal neck, balloon 32 may evert, pushing the everted portion outward to an extended position and into contact with the tubal lining cells. In some embodiments, upon full balloon eversion, extension 34 may extend out of the distal neck of the fallopian tube and into the abdominal cavity. In some embodiments, the extension 34 may have an expanded outer diameter of about 5-15 mm.

An advantage of having a plurality of bristles on the extension 34 is that the surface area over which the sample (e.g., cells and/or tissue) can be collected can be increased, including areas that are less likely to be exposed to shear forces when the device is retracted within the catheter. Thus, cell collection can be maximized and the amount of cells scraped off when the device is pulled through the fallopian tube or into the sheath is minimized, as shown in fig. 18-20. In embodiments where the extension has a larger surface area, cell collection per linear unit of fallopian tube so engaged under similar pressurization conditions may be increased as compared to an uncontoured extension.

In still other embodiments of catheters according to the present disclosure, the extension portion, such as the expandable member, may form any number of shapes and contours. For example, a plurality of filaments 42 may be attached to the distal end of balloon 32, which expand to form brushes 42 when the balloon is everted (fig. 11A-11B). In some embodiments, braided string or suture 43 may extend distally of balloon 32 when everted (see fig. 11C-11D), and in other embodiments, the braided suture may be formed of various materials and/or may have one or more colors for visual confirmation of the extension of suture 43 (see fig. 11E-11F). Polymer foam structure 46 may be compressed within bladder 32 and may self-expand in response to eversion of bladder 32 and exposure to a fluid environment (fig. 12A-12B). An elastic or inelastic balloon 48 may be provided on the distal end of the inelastic sleeve balloon 32 (fig. 13A-13B). Alternatively or additionally, some embodiments may include an everting balloon with superelastic coils (fig. 14A-14B), a helical everting balloon 50 (fig. 15A-15B), an everting distal arcuate balloon 52 (fig. 16A-16B), or long polymeric or metallic elastic filaments (fig. 17A-17B) that are polymerized into a three-dimensional structure, such as an inner lumen 54, when the balloons are everted, and an expandable member 34 with a plurality of outwardly-oriented bristles 40 (fig. 18), or combinations thereof. It will be appreciated that the catheter extension as an expandable member or any of these other embodiments may include fiducial markers as a navigation aid for a medical professional to navigate back to a desired location in the fallopian tube. For example, the marker may be delivered to a desired location in the fallopian tube, e.g., through the inner lumen 54 or through the balloon 32. Such markers are well known in the art and include, by way of example, radiopaque markers, isotopic markers, and radio frequency markers. In still other embodiments, the biodegradable extension or the permanent extension may be detachable from the catheter. In still other embodiments, the extension portion can deliver a therapeutic agent, such as a chemotherapeutic agent, an antibiotic, an anti-inflammatory, or a combination thereof, to the tubal tissue.

When the catheter is retracted into the working channel of the hysteroscope, cells can be removed from at least a portion of the entire length of the inner surface of the fallopian tube. In some embodiments, the collected cells may be shielded with openings inside the end region of the catheter by reducing the gas pressure inside the balloon to invert the extension back inside the balloon and re-invert the balloon into the end region of the catheter. In other embodiments, the extension and balloon (in a deflated state or remaining inflated) may be retracted into the sheath without the need to re-invert the balloon. For example, as shown in fig. 19, an extension 34, such as an expandable filament 38 including a plurality of bristles 40, may be protected by a sheath 162 during removal from the patient (see fig. 23A).

An extension 34, such as an expandable filament 38 shown in fig. 18-20, may be attached to one end of the inverted balloon. In some embodiments, an extension 34, such as an expandable coil, may be connected to the push wire (see fig. 23A). In some embodiments, the extension portion may be connected to the distal end of the push wire 134. In some embodiments, the extension 34 (e.g., a spiral) may be a collection device that passes through the inner lumen, which may expand when reaching the distal end of the fallopian tube. It will be appreciated that cells may be collected from a particular portion of the fallopian tube (e.g., the umbrella) and then protected by the sheath 162 in order to minimize the likelihood that distal cells will be scraped off by the inner surface of the proximal fallopian tube when the device is removed.

In some embodiments, the friction between the outer surface of the extension 34 (e.g., the expandable filament 38) and the inner layer of the fallopian tube is sufficient to dislodge cells and adhere those cells to the expandable member, even in embodiments having an uncontoured extension. For example, an inflation spiral at the distal end of the balloon may contact an umbrella at the distal end of the fallopian tube to collect a cell sample. Since the inner diameter of the fallopian tube increases as it extends from its proximal side to its distal end, the expansion of the extension portion 34 (e.g., by the expandable filament 38) may maximize the cell sample taken at the distal end of the fallopian tube (e.g., the umbrella portion of the fallopian tube).

In some embodiments, the elongate balloon and the extension may be retracted into the working channel of the hysteroscope to avoid loss of the cell sample when the hysteroscope is removed from the patient. An elastomeric seal at the proximal end of the working channel of the hysteroscope may seal the outer surface of the catheter. Such a seal may be used to prevent the catheter from sliding from a desired location within the working channel of the hysteroscope, or from sliding completely out of the working channel. The markings on the catheter body may indicate the length of retraction required to ensure that the elongate balloon and distal helix are fully within the hysteroscope working channel. Upon removal of the hysteroscope from the patient, in some embodiments, a syringe containing a saline solution may be attached to the luer fitting at the proximal end of the working channel. Saline may be used to flush cells collected by the elongate balloon and the inflation helix into the tube. It will be appreciated that cells collected by the inflatable member may be collected for detection by conventional techniques and may be prepared for cytological, molecular or genetic examination.

In some embodiments, the inner lumen 54 may be formed of a material having sufficient rigidity to maintain an opening in the lumen. For example, inner lumen 54 may be sufficiently rigid to withstand the pressure of the balloon as it expands and everts. In some embodiments, the inner lumen 54 may be formed of a metal, composite, or polymer, or a combination thereof, including polyethylene terephthalate (PET) materials, and may be attached to a catheter, as shown in fig. 17A-17B. The eversion process follows that of the above-described embodiment with a push wire that does not include a lumen. This embodiment may also include an inflation side port and proximal seal 33 that may allow balloon 32 to evert while maintaining fluid communication between the hysteroscope and the patient's body tissue through the port of inner lumen 54. Once everted, the inner lumen 54 may provide a path through which a separate extension may pass, or through which a surgical instrument package or visualization device may pass. In some embodiments, various agents may come into contact with the lumen via this path. Thus, these agents and rationale may illustratively include microbubbles for use as acoustic contrast agents, imaging agents for various forms of spectral imaging, or therapeutic agents for treating or killing cancer cells, or combinations thereof. The therapeutic agent may illustratively include an antibody specific to the cancer cell and carrying a chemotherapeutic agent or radioisotope, a chemotherapeutic agent, a radioisotope seed, an antibiotic, an antifungal agent, or a combination thereof.

Figures 21A-21B illustrate cross-sectional views of an exemplary embodiment of a spherical end eversion balloon catheter 120 according to the present disclosure. Spherical ball 122 may be attached to the distal end of a spring tip 124 secured to a tube or catheter 126. It should be understood that "tube" and "conduit" 126 may be used interchangeably. A spherical ball 122 may be provided to travel through the UTJ of the patient to minimize and/or avoid inadvertent penetration of the sidewall of the UTJ. Spring tip 124 may allow the distal end with ball 122 to bend around a corner and travel through the UTJ. Spring tip 124 and spherical ball 122 may have an open lumen 128 that may extend through spring tip 124 and spherical ball 122. The spherical ball 122 on the spring tip 124 may be about 0.8-1.0mm in diameter, and the hollow spring tip 124 may be about 1.5cm in length and about 0.6mm in outside diameter. The hollow spring end 124 may be formed of a metal (stainless steel or super-elastic metal, such as nitinol) coil spring and is sheathed on the outside with a thin-walled polymeric heat-shrinkable tube made of nylon, PET (polyethylene terephthalate), or similar material. In some embodiments, the spring tip 124 may be a metal coil spring coextruded into a tubular polymer body. The hollow spring tip 124 may also be a flexible polymer tube, and in some embodiments may be made of nylon, polyethylene terephthalate (PET), polyether block amide, or similar materials. An everting bladder 130 may be located within the hollow spring tip 124. The everting balloon 130 may extend proximally into a main lumen 132 of a cannula (e.g., a generally rigid tubular structure) or an introducer catheter 126 (e.g., a generally flexible tubular structure).

The proximal end of the everting balloon 130 may be attached to a push rod 134, the push rod 134 may pass through a seal 135 on the proximal end of the cannula or conduit 126. In operational use on a patient, the flexible ball-shaped tip 122 may be manually advanced through the UTJ. Once the flexible ball tip 122 and spring tip 124 pass through UTJ, the pushrod 134 may be advanced through the seal 135 of the previously pressurized cannula or introducer catheter 126. Advancement of the pushrod 134 may cause the balloon 130 to controllably evert out of the hollow spring tip 124 and through the length of the fallopian tube.

According to some embodiments, a seal 137 may be disposed within the tube/catheter shaft 126, the push wire 134 traveling through the seal 137 when the push wire 134 actuates the balloon (see fig. 21B, 23A). In some embodiments, the seal 137 may be a conical seal disposed between the pressurization chamber 116 and the push wire 134. It should be noted that the terms "push wire" and "push rod" are used synonymously herein. The conical seal 137 may allow the push wire 134 to travel through the conduit 126 to actuate the balloon 130 between the everted and inverted positions while maintaining pressure in the conduit 126. Various embodiments of the present disclosure may provide an adjustable seal 135 disposed adjacent to a conical seal 137. In response to a leak developing between the push wire 134 and the conical seal 137, the adjustable seal 135 may be adjusted to maintain the pressure required to move the bladder between the first everted position and the second everted position. The adjustable seal 135 may be a rotary hemostasis valve (e.g., a device for maintaining a seal between coaxial devices) and may be adjusted by a knob 133. In some embodiments, a hemostatic valve may be used as the seal 135. The hemostatic valve may include a compressible gasket to provide a desired degree of sealing.

The knob 133 may be rotatably adjustable to adjust the seal 135. In use, a user can adjust the knob 133 to tighten or loosen the knob 133. By tightening the knob 133, the seal 135 may be compressed, thereby collapsing around the push wire 134. The rotatable knob 133 may provide the user with improved control over the seal and the ability to react in the event of any leakage from the conical seal 137.

In some embodiments, the elongate balloon may be initially everted into the catheter lumen during assembly, e.g., the balloon may be everted inside out during assembly. The balloon may be pressurized for deployment such that the balloon everts and "deploys" into the fallopian tube. The everted deployment mechanism can track through the fallopian tube regardless of the tortuosity or constriction in the fallopian tube. The majority of the length of the balloon may be substantially inelastic, e.g., up to 100% of the length of the balloon, such that the balloon does not substantially inflate and expand when everted, e.g., so that the fallopian tube does not inflate or expand when the balloon is everted. In other embodiments, a portion of the distal end of the balloon may be expandable into the umbrella end of the fallopian tube (see, e.g., fig. 5-8). Over inflation of the balloon may rupture or damage the fallopian tube.

An exemplary procedure common to various embodiments of the device may include deployment of the distal end of the catheter. In some embodiments, the catheter distal end may be delivered to the proximal end of the fallopian tube through a conventional hysteroscope. Regardless of the mode of deployment, the retracted portion of the balloon within the catheter shaft 126 may extend from within the catheter shaft 126 into contact with the inner wall of the fallopian tube. It has been surprisingly found that the act of extending the portion may abrade a sufficient amount of cells and/or tissue from the fallopian tube wall for histological evaluation. This was observed for the flat surface of the balloon with features that appeared to be non-abrasive. Although in some embodiments, a rough surface texture on the balloon may be included for contacting the fallopian tube wall, the surface of the inelastic balloon portion may be sufficient to remove a sufficient amount of cells and/or tissue for statistically meaningful histological evaluation, whether the balloon is fully inflated or partially deflated and deflated. It has also been surprisingly found that retracting the extension removes more cells. In other embodiments, the extension portion may be retracted prior to catheter removal to prevent the dislodged tubal cells from spreading to the surrounding tissue. With the catheter removed, contacting the exposed portion of the extension (now covered with cells) with a microscope slide or other diagnostic substrate may be sufficient for detection of abnormal cells, and in particular cancerous cells.

The catheter 126 described above (and described in more detail below) can be introduced into the patient's uterus using a surgical hysteroscope 20, an example of which is shown in fig. 3. The surgical hysteroscope 20 may include one or more working channels. One working channel may provide irrigation to enlarge the uterus and allow for endoscopic visualization, and one or more additional working channels may allow for distal advancement of instruments and/or catheters to the hysteroscope. A catheter 126 (e.g., fig. 21A and 21B) may be advanced through the working channel of the surgical hysteroscope and may cannulate the proximal neck of the fallopian tube. The everting balloon 130 may be advanced through the proximal catheter 126 to the proximal portion of the fallopian tube.

Figures 22A-22C illustrate an exemplary embodiment of everting balloon 130 according to an embodiment of the present disclosure, everting balloon 130 exiting from flexible tip 152 with spherical ball 122. Nylon flexible tip 152 and spherical ball 122 may be configured to travel through the patient's UTJ for deployment of everted balloon 130 in the fallopian tube. In one embodiment, the spherical-tip eversion balloon catheter 150 may be configured with a spherical tip of about 0.9mm on a tip having a diameter of about 0.66mm X a length of 18 mm. In some embodiments, the tip may be formed of nylon. In some embodiments, a 4Fr catheter has a balloon with a diameter of 0.64mm that can be everted through and beyond the tip.

Fig. 23A-23B illustrate side cross-sectional views of a balloon-tipped catheter or device 160 according to the present disclosure. In some embodiments, balloon 130 may have an outer diameter of about 0.8-1.0mm, and may have an initial eversion length of about 1-3cm (e.g., about 1.2-1.5cm extending from the distal end of cannula or conduit 126). Balloon 130 may be fully evertable into the fallopian tube, e.g., extending about 7-12 cm. Balloon 130 may be secured to the distal end of catheter shaft or tube 126 (as indicated by reference numeral 117) and push wire 134 (as indicated by reference numeral 118). For example, distal end 118 of push wire 134 may form one end of balloon 130. In some embodiments, balloon 130 may be bonded to distal end 118 of push wire 134. When the interior of the balloon, between the catheter 126 and the balloon 130 and indicated by reference numeral 119, is pressurized, a push rod or wire 134 may actuate the balloon 130 from an everted position in the catheter 126 to an everted position. In some embodiments, the everted position may include at least a portion of balloon 130 extending beyond the distal end of tube 126. In some embodiments, balloon 130 may be initially partially everted and secured to catheter 126, forming a rounded end 130 a. In some embodiments, balloon 130 may be inflated with fluid to a pressure of about 14-24atm (206-.

In some embodiments, as described above, the device 160 may include a sheath 162. The sheath 162 may be coaxial with the catheter 126. Sheath 162 may be slidably adjustable relative to catheter 126 to cover at least a first length of balloon 130 extending outwardly from the distal end of tube 126 in the everted position. Sheath 162 may form a physical barrier between balloon 130 and the interior of the endoscope to protect the balloon. For example, during insertion through an endoscope, balloon 130 may extend an initial length (e.g., about 1.5cm) from catheter 126. The sheath 162 may protect the balloon when the balloon is actuated (e.g., via push wire 134 and/or balloon pressurization) in at least one of an everted position, a partially everted position, or a fully everted position, or a combination thereof.

The sheath may also provide column strength to the balloon when it is everted. In some embodiments, a portion of the sheath 162 may be at least partially translucent, optically transparent, or a combination thereof, as shown at reference numeral 162 a. In some embodiments, the transparent portion 162a of the sheath 162 may at least partially overlap the transparent portion 167 of the catheter 126. For example, a medical professional may be able to visualize the balloon 130 (e.g., to confirm positioning and/or full balloon extension) through at least a portion of the sheath 162 and/or catheter 126 using the hysteroscope 20. In some embodiments, the catheter may include a sheath knob 164 at the proximal end of the sheath 162 to connect the sheath 162 to the tube 126.

The pressurizing balloon 130 may have a rounded end 130a for atraumatic cannulation and travel within the fallopian tube of the proximal neck, and a degree of flexibility along the length of balloon 130. Balloon 130 may have sufficient column strength to allow balloon 130 to be manually advanced through the UTJ with at least partial or no pressure, for example, using push wire 134. In some embodiments, bladder 130 may be constructed of a thin-walled polymeric material, such as polyethylene terephthalate (PET), polyethylene, nylon, a polymer, or the like. The wall thickness of balloon 130 may be from about 0.0001 inches to 0.001 inches, and in some embodiments between about 0.00019 inches to 0.00031 inches. In some embodiments, bladder 130 may have a thickness of less than 0.005 inches. The material and/or thickness of the balloon may be important characteristics of the balloon that affect how the balloon functions when deployed and in cell collection. For example, too thin a bladder wall may result in the bladder lacking sufficient column strength (being more compliant or elastic as desired), or too thick a bladder wall may result in the bladder everting or resisting eversion in an inconsistent manner. The thickness of the material can affect the topography, wrinkling of the balloon surface such that when the balloon is loaded into a catheter, the inversion action creates or enhances surface features, which in turn can affect the ability to collect and retain cells. The material of the balloon may also affect whether the balloon will stick or tend to stick to itself during eversion or after catheter contraction and retrieval.

In some embodiments, the first indicia 171 may be disposed on at least a portion of the conduit 126. The first indicia 171 may be a ready indicia indicating a desired position of the sheath knob 164. When the sheath knob is aligned with the first indicia 171, the proximal end of the sheath 162 may be a reference point for the medical professional to extend over the balloon during preparation and initial intubation of the balloon 130 into the fallopian tube. In some embodiments, at least a portion of catheter 126, such as a proximal portion connected to transparent portion 167, can be formed of a metal, such as stainless steel, or other material, such as a composite or polymer, or a combination thereof. The first indicia 171 may indicate to the user the proper position of the male luer lock or sheath knob 164 relative to the balloon 130 within the sheath 162 so that the sheath 162 may be extended distally an initial length as a preparatory step to cover an everted balloon 130, for example, of about 10 to 20mm length for accessing the proximal neck prior to full eversion of the balloon.

When in place at the proximal neck opening, the sheath can be pulled back from the first indicia 171 to the initial position, thereby exposing the partially everted balloon tip for access and placement in the fallopian tube. In some embodiments, the sheath 162 may extend along the longitudinal axis to a point beyond the distal end of the catheter 126. When the sheath 162 extends distally of the catheter 126, the distal tip of the sheath 162 may be an indicator of balloon advancement. The first indicia 171 may include score lines, coating substances, or selectively oxidized regions. In some embodiments, the first indicia 171 may be a band of opaque material (e.g., including, but not limited to, a polymer, or a metal, or a combination thereof) that may be attached to at least a portion of the conduit 126 (e.g., a metal portion or the hypotube 138) using, for example, an adhesive, bonding, or welding process. Such priming marks may allow a medical professional to know how far to deploy balloon 130 in an initial priming step, thereby improving the ease of use of the device by eliminating the need for external measurement tools, and improving the safety of the surgical procedure by eliminating any guessing or visual observation on the part of the user.

In some embodiments, the markers may be progressively spaced apart from each other by a known predetermined distance such that a health professional may use the markers as a visual counter or measuring device to determine the approximate length of the balloon that has been everted. It should be understood that any of the cannulas or catheters described herein may include indicia as described for assisting in navigating through the anatomy of a patient.

In some embodiments, a second marker 173 may be provided on the catheter 126, such as on the metal portion 138, to indicate the desired position of the sheath knob 164 to confirm that the sheath 162 covers the everted portion of deployment (balloon, suture, etc.) during movement of the device into the hysteroscope 20. For example, the second mark 173 may be a retraction mark. This may allow the user to visualize and confirm that the balloon 130 is fully protected by the sheath 162 during the removal process to avoid loss of cells collected on the balloon and/or the extension. The additional user visualization provided by the second indicia 173 may be advantageous when the hysteroscope view is obscured by, for example, tissue or blood in the distending fluid. The second mark 173 may be formed by the same technique used to form the first mark 171. Second indicia 173 may also be included on any of the interpolators or catheters described herein.

In some embodiments, the portion 167 of the catheter 126 and/or the distal portion of the sheath 162 may have a transparent portion along its length, or a portion that is translucent, optically transparent, or a combination thereof, under conditions of use. According to embodiments of the present disclosure, the tube or conduit 126 may include at least one visual marker. In other embodiments, the visual indicia on the catheter 126 may include a third indicia 179 disposed on the catheter 126. The third marker 179 may be located at or near the distal end of the shaft of the catheter 126 (where the balloon 130 is connected to the catheter 126). In some embodiments, the third indicia 179 can be radiopaque. The third indicia 179 can visually indicate to a user the end of the shaft of the catheter 126, thereby improving control of the catheter 126. During intubation, it may be desirable for the end of the catheter 126 to be visible as the balloon 130 travels beyond the sheath 162 into the fallopian tube. As the intubation procedure progresses, the third marker 179 may allow the user to visualize the distal end of the catheter 126. The user may be able to see when the intubation procedure is complete, e.g., when the third marker 179 is aligned with the end of the sheath 162 at the neck finish, thereby improving ease of use. The third indicia 179 may be formed by the same techniques used to form the first indicia 171 and/or the second indicia 173. The third indicia 179 may be provided in a readily visible color (e.g., black or blue).

In some embodiments, the string, braid and/or suture 121 may extend distally of balloon 130 when balloon 130 is everted in the form of an extendable portion of balloon 130. In some embodiments, the string or suture may be attached to the distal end of the push rod or the balloon tip (e.g., at reference numeral 118) by bonding or adhesive. In the inverted position of balloon 130, the string, braid and/or suture 121 may be positioned inside balloon 130, for example, within the tube of catheter 126, as shown in fig. 23A. When balloon 130 is everted, such as by actuation of a push rod, the string, braid and/or suture may extend to a location that becomes external to the balloon, extending distally from the distal tip of balloon 130, or proximally from the balloon tip near the balloon exterior.

In some embodiments, at least a portion of the string, braid, and/or suture 121 (e.g., as shown at reference numeral 43 in fig. 11C-11D) may be braided. The braided string or

suture

43, 121 may include one or more filaments. The string or

suture

43, 121 may be extended when the

bladder

32, 130 is everted. In some embodiments, the string or

suture

43, 121 may be a plurality of braids. In some embodiments, the strings or

sutures

43, 121 may be formed of one or more colors, for example, to enhance visibility for a medical professional to confirm that the balloon is being everted properly (see fig. 11E-11F). For example, when the balloon is everted and the string or

suture

43, 121 is pushed out with the balloon, the color can be visualized through the endoscope. As the

balloon

32, 130 everts, the string or

suture

43, 121 inside the

balloon

32, 130 may extend out of the balloon at about twice the distance as the balloon everts (e.g., about 2mm of string or suture is exposed out of the distal end of the inner cannula/tube when the balloon is everted 1 mm). The color may determine the location of the suture or

string

43, 121 in the fallopian tube for sample collection. In some embodiments, the string or

suture

43, 121 may include one or more regions having printed indicia or a color change along its length, or a combination thereof. In some embodiments, the string or

suture

43, 121 may include one or more knots spaced at predetermined known increments along its length to provide further visual or tactile feedback to the medical professional (see fig. 34A-34B). The colors and/or knots may be arranged at increasing distances from each other such that the count of colors or knots may be converted into an approximate amount of distance/length that the suture or string 43, 121 (and to some extent the length of the balloon 130) has everted.

In some embodiments, the balloon material may be treated to alter the surface properties of the outer surface of balloon 130. Processes such as plasma or corona treatment can increase surface acceptance of a variety of substances, including, illustratively, test cells, inks, coatings, adhesives, laminates, and coatings, or combinations thereof. Surface treatments may enhance wettability, resulting in a surface with hydrophilic properties, or block wettability, resulting in a surface with hydrophobic properties. Surface treatment may be used to improve the adhesion properties of the capsule surface to produce a surface to which cells adhere more readily than an untreated surface.

Surface treatment may also be used to prepare the capsule surface for printing indicia on the surface, including PAD printing, for example. PAD printing, also known as overprinting (tampgraphics), is a printing process that can transfer two-dimensional images onto three-dimensional objects. The indicia printed on the surface of the capsule may serve as priming indicia for the user. These priming marks may allow the user to know the length of balloon 130 prior to deployment of balloon 130, thereby improving the ease of use of the device by eliminating the need for external measurement tools, and improving the safety of the surgical procedure by eliminating any guessing or visual observation on the part of the user.

In addition to markings for visualization purposes, balloon 130 may also be treated with a process that increases surface area, such as applying a nanofiber or micropillar surface (such as, including but not limited to, Corning corporation's (Corning) surface

) This may improve cell collection yield and/or retention compared to capsules with little or no surface treatment. Suture or string 121 may include similar surface treatment features as a way to enhance cell collection and retention.

In various embodiments, bladder 130 may be formed from the following materials: the material enables the balloon 130 to move between the everted and inverted positions without excessive deployment pressure, yet be sufficiently rigid that the balloon does not expand excessively radially during eversion. The material may also allow wrinkles, overlapping material or micro-ridges or combinations thereof to be formed on the balloon surface during manufacturing and/or assembly, for example by polymer deformation. Such wrinkles, overlapping material, or micro-ridges may be created on the capsule surface material, which is generally smooth (not contoured), or may enhance the capsule surface material already including one or more surface features. The folds, overlapping material or micro-ridges formed in the balloon material may be maintained during eversion and/or inversion of the balloon, e.g. the balloon surface may be plastically deformed. The folds, overlapping material and/or micro-ridges may improve cell collection of the capsule 130. For example, cells may be removed from the fallopian tube during balloon eversion and/or may be captured within the folds (as balloon 130) so that when balloon 130 is retracted into sheath 162 and catheter 126 is removed with the endoscope, the cells may remain within the folds of balloon 130. Relieving the pressure in the capsule prior to deflation, deflating or partially deflating the capsule, may increase or reform wrinkles on the surface of the capsule and further improve cell collection and/or retention. In some embodiments, the surface of balloon 130 may be roughened, or otherwise modified, to increase the surface area. According to various embodiments, the bladder may be made of polyethylene terephthalate (PET), polyethylene, nylon, fluoropolymers, or perfluoropolymers, or other similar suitable materials.

In some embodiments, a surface region of balloon 130, such as a surface for contacting an inner surface of a body lumen (fallopian tube), may include additional surface features. In some embodiments, the capsule surface, which is relatively smooth due to material properties, may be modified to include corrugations and increased surface area, for example by processes employed during manufacture or packaging that apply surface features to the capsule surface and remain during use of the device. In other embodiments, the retained balloon material surface, which is relatively free of any topography, may still be able to collect and retain cells simply by everting the tissue lumen and engaging it with the balloon as described above, and then (optionally deflating the balloon and) retracting the balloon along the tissue wall. In some embodiments, the surface of bladder 130 may be embossed to impart micro-ridges having peak-to-valley heights of about 0.1 to 500 microns by various conventional techniques, including, illustratively, plate-to-plate, roll-to-plate, and roll-to-roll. In some embodiments, the peaks and valleys may be configured to be large enough to provide additional surface area, but small enough to minimize the likelihood of the peaks and valleys locking together. For example, during inversion/eversion, peaks and valleys in the balloon surface area may interlock such that balloon movement may be impeded. Thus, it may be advantageous to configure the peaks and valleys to have profiles that minimize potential interlocking.

In some embodiments, the polymer surface of bladder 130 may be etched. Etching may be accomplished by a variety of conventional techniques, including but not limited to solvent, chemical, laser, or plasma exposure. Etching may be beneficial to increase the surface area without creating stress on the bladder with which the imprinting tool is in contact. This feature may improve the cell collection of the balloon by increasing the surface area and creating a micro-edge that is orthogonal to the axis of the balloon when the balloon is removed. In some embodiments, as described above, polymers with low surface energy and/or limited ability to curl/wrinkle at any balloon thickness when stamped and/or etched are still useful herein for cell biopsy because the opposing contact surfaces have sufficient slippage to allow smooth eversion of the balloon while having sufficient surface area to dislodge and retain cells. The low surface energy polymer in the form of an imprint or etch may include a fluoropolymer, a perfluoropolymer, a polyalkylene, a polypyrrole amide (Kapton H), or a polystyrene, or a combination thereof.

In some embodiments, the etching or embossing may be formed on the surface of the capsule in a concentrated portion of the capsule, for example as a logo. For example, the balloon markings may provide a visual indication to a medical professional to determine the extent to which the balloon extends into the fallopian tube. The medical professional can see a focused etch and/or embossing, for example, potentially eliminating the need for separately attached markings or other indicia. Indicia formed as part of the balloon may be beneficial to minimize and/or avoid potential detachment.

Bladder 130 may be translucent, optically transparent, or a combination thereof. In some embodiments, balloon 130 may be at least partially opaque to enhance visibility during use. In some embodiments, an opaque fluid may be mixed in the inflation fluid to control the color of the balloon and further enhance visualization of the balloon. The amount of opaque fluid added to the inflation fluid may control the degree of translucency or opacity of the balloon. In some embodiments, the fluid may be rendered opaque or otherwise detectable by inclusion of microbubbles or colloids or suspended particles released within the fluid. Colloidal or suspended particles useful herein include, but are not limited to, polymethylmethacrylate, mica, barium sulfate, starch, and combinations thereof.

The length of the fully everted balloon 130 may extend within the lumen (e.g., fallopian tube) to about 7-12cm, such that when fully everted, the balloon 130 may extend within the patient's fallopian tube as at least a portion of the length of the everted balloon successfully travels through the UTJ. Eversion of balloon 130 may be performed in a controlled manner, for example, by advancing push rod 134 through fluid-tight seal 135 at the proximal end of catheter 126. As described above, at least a portion 167 of catheter 126 may be transparent or translucent such that movement of balloon 130 may be observed through a hysteroscope into which catheter 126 is inserted, thereby providing a direct view of the insertion process for the user. The conduit 126 may be constructed of a polymer, such as nylon, polyether block amide, polyurethane, PET (polyethylene terephthalate), polyethylene, or polyvinyl chloride (PVC), with or without polymer or metal coils or braided reinforcements, or combinations thereof.

In some embodiments, the length of the transparent or translucent portion 167 of the catheter 126 may be at least about 1cm for visualizing balloon deployment through hysteroscopic viewing angles. Providing a sufficient length of the transparent or translucent portion 167 may ensure visualization of balloon deployment while providing sufficient catheter column strength for tubal intubation. In some embodiments, the transparent portion 167 of the catheter 126 may have a length relative to the opaque portion (e.g., the metal hypotube portion 138) to balance desired column strength and support for the catheter 126 in the case of visualization at the distal end. In some embodiments, transparent portion 167 may extend within metal portion 138 to the proximal end of the device. It should be appreciated that the material used to form transparent portion 167 of conduit 126 may have a lower column strength than metal hypotube portion 138. This balance may improve the ease of use (e.g., by visualization of the distal end) and control of the device (e.g., by having sufficient rigidity to allow the device to be placed at the ostium of the fallopian tube and remain in place throughout the procedure).

In some embodiments, balloon 130 may not remain straight when balloon 130 is at least partially everted out of catheter 126 or cannula. Conversely, balloon 130 may assume an undesirably curved configuration, either a single "C" curve or an "S" curve, which may be difficult to use for cannulating the proximal neck of the fallopian tube and advancing the balloon through the UTJ. The extended length of everted balloon 130 may be straightened or held straight by the use of an outer sheath 162, the outer sheath 162 being coaxial around the outside of the catheter 126 or cannula and may assist in providing column strength and coverage of the partially everted balloon ends. At least a portion of sheath 162 and/or catheter 126 may be a transparent portion 167, such as 167 of fig. 23A, such that movement of balloon 130 may be observed through a hysteroscope through which the catheter is inserted, thereby providing a direct view of the insertion process for the user. Similar to the catheter 126, the sheath 162 may be constructed of a polymer, such as nylon, polyether block amide, polyurethane, PET (polyethylene terephthalate), polyethylene, or polyvinyl chloride (PVC), with or without polymer or metal coils or braided reinforcements, or combinations thereof. The sheath may be alignable relative to the catheter and/or balloon to provide column strength to the balloon. In response to the balloon entering the fallopian tube through the UTJ cannula, the sheath may support the balloon from the proximal exterior to minimize and/or prevent collapse as the balloon is further everted after navigation through the UTJ. The sheath 162 may also protect the sample (e.g., cells) collected on the balloon and/or the extension. For example, sheath 162 may protect the balloon in an everted position after contacting the inner surface of the fallopian tube. In some embodiments, the balloon and sheath 162 with or without an extension may be retracted coaxially with the inner lumen of the sheath to extend the sheath over the everted balloon and extension (if included) after cell collection. In some embodiments, the sheath 162 may remain stationary relative to the balloon 130 and/or catheter 126 such that the balloon 130 is received in the sheath 162 after cell collection. When the balloon 130 is withdrawn within the sheath and removed from the patient, the sheath may protect the cells to minimize and/or prevent loss of sample collection by providing a barrier to the distending fluid in the uterus or the flushing fluid in the fallopian tube or uterus. For example, the capsule after cell collection may be exposed to environmental conditions, which may render sample collection unusable and/or otherwise wash cells from the capsule and extension.

Fig. 35 illustrates an exemplary embodiment of linear eversion of bladder 130 according to the present disclosure. In some embodiments, one end of the balloon may be fixed to the inner cannula/tube at point X (e.g., reference numeral 117 shown in fig. 23A) and the other end of the balloon may be movable at point Y (e.g., reference numeral 118 shown in fig. 23A). Bladder 130 may be everted from the position shown in step 1 to the position shown in step 2 and then everted to the position shown in step 3. During eversion, points a, B, and C move to the left in the figure, e.g., extending distally of the distal end of device 160. Point a may move from the inner surface to the outer surface of the bladder as the bladder 130 expands/everts at/toward the left side of the figure. In practice, balloon 130, which has been partially or initially everted during the preparation step, may be advanced further to the proximal end of the fallopian tube. Further eversion (extension) of the balloon can be achieved by further rotation of the drive wheel 204 (see fig. 25) (total to the full length of the fallopian tube, approximately 7-12 cm). Balloon 130 may then be deflated by relieving pressure in the inflation device. Balloon 130 may then be retracted from the fallopian tube. Because the fallopian tube is a potential space, the fallopian tube tissue may collapse around the balloon. Because the balloon fills the fallopian tube, the balloon surface area may be approximately equal to the surface area within the fallopian tube. This surface area may optimize tissue collection inside the fallopian tube. While the contraction of the balloon prior to retraction may be desirable, in some embodiments, the balloon/extension may be retracted from the fallopian tube without first contracting the balloon and still retaining the cells collected thereon. For example, balloon 130 in the inflated and/or deflated state may be retracted within sheath 162 while maintaining a sufficient amount of cells on the surface of balloon 130 for detection. Alternatively, the balloon may be repeatedly inflated and deflated while extending in the fallopian tube, such that the balloon may collect and/or hold more cells each time the balloon contacts the fallopian tube wall.

As already mentioned, to further assist tissue collection, folds or other surface features may be added to the balloon surface. Folds may be formed when the balloon is deflated to create multiple edges and/or overlapping material to aid in cell collection. The edge may function in a manner similar to the edge of a curette or the edge of a jaw in a bioptome. Similar to these features on other collection devices, the edges formed by the pleated balloon can focus the contact force on the anatomical wall for cell collection.

The balloon deployment device according to the present disclosure may then be removed from the working channel of the hysteroscope and the patient. Once the device is removed from the patient, the cells may be removed from the capsule by immersing the capsule and/or the extension (if used) in a cytological preservative and shaking to agitate the cells. Alternatively, the balloon, extension and/or sheath may be cut out and placed in a cytological preservative. In some embodiments, a sheath may be extended and deployed over the balloon to protect tissue samples collected on the surface of the balloon when the balloon is deflated and removed.

Fig. 24 shows a side cross-sectional view of a balloon tip catheter 160' including a superelastic pushrod 175 and a helical carrier 176. According to embodiments of the present disclosure, the helical carrier may minimize and/or eliminate the need to extend the push rod rearward (e.g., outside the handle) over the entire length of the push rod. Pushrod 175 may be constructed of a superelastic material, such as nitinol (nickel titanium compound) wire. At least a portion of the length of pushrod 175 may be wound into a coiled tubular carrier 176, which may be made of polyethylene or polytetrafluoroethylene (teflon). The outer helical diameter of the carrier is about 8cm, making the proximal operating length of the catheter handle more compact. The spiral carrier 176 may be attached to the proximal seal 135 on the catheter by a flexible band 177. In some embodiments, the flexible band 177 may be constructed of a polymer or silicone rubber material. In some embodiments, the push rod 175 may have a diameter of about 0.025 "or some other thin diameter, which may be disadvantageous for the purpose of grasping the wire and pushing it forward through the seal 135. A flexible grip 178 may be included that slides freely on the pusher 175, but when compressed between the thumb and forefinger, a grip for travel of the pusher 175 may be provided. The flexible grip 178 may be an oval cross-section frame, which may be made of polyvinyl chloride, silicone rubber, or a combination thereof, or similar flexible compounds. In some embodiments, the flexible grip may have internal dimensions of about 2cm long, 1cm wide, and 3mm high, and may have a wall thickness of about 2 mm. The holes on the proximal and distal sides of the grip portion may be a sliding fit with pusher bar 175.

Fig. 25 shows an exemplary embodiment of a balloon-tip catheter 200 configured with a handle 202. In some embodiments, a handle 202 may be included in the device 160, as shown in fig. 23A. The handle 202 may house a gear mechanism 220 (see fig. 26A-26B), also referred to herein as an actuator. The handle 202 may be in mechanical communication with the

push wires

134, 206 and may control actuation of the

push wires

134, 206, which in turn may control actuation of the balloon 130 between the everted and inverted positions. Handle 202 may include drive wheels 204 for advancing and retracting

push wires

134, 206, wherein balloon 130 may be linearly everted (e.g., progressively opened or deployed from the inside out). The drive wheel 204 may be made of a polymeric material, including but not limited to Acrylonitrile Butadiene Styrene (ABS). The outer edge of the drive wheel 204 may include a notch or knurl pattern to facilitate gripping of the wheel during operation of the catheter 200. The outer edge of the drive wheel 204 may include a number of features shaped like arrows that facilitate gripping and/or may indicate the proper direction of travel of the drive wheel. The top surface of the drive wheel 204 may have arrows molded into it to indicate the correct direction in which to turn to evert the bladders. The opposite side of the drive wheel 204 may include a square boss 222 that may be inserted into a drive gear 224. In some embodiments, the gear mechanism 220 may include reduction gearing that provides a reduced amount of extension of the

push wires

134, 206 relative to a given rotational distance traveled by the drive wheel 204 (i.e., the drive wheel 204 must turn a greater distance to achieve the same protrusion length of balloon eversion than if the reduction gearing were not included or a different reduction ratio was included). The net effect may be a finer control of eversion of bladder 130 as drive wheel 204 rotates.

Catheter 200 may retain balloon 130 in shaft 210 (which may be formed at least in part from stainless steel tubing and/or nylon tubing), sheath 212, and/or sheath knob 214. For balloon travel, the balloon 130 and shaft 210 may be pressurized with an inflation device (such as inflation device 172 of fig. 23C) that may be attached to the

extension tubes

168, 216 or luer fitting 218 of the handle 202 (see fig. 26A-26B). Once the catheter device 200 is pressurized, the user may rotate the drive wheel 204, causing the

push wires

134, 206 to travel. Although in some embodiments, balloon 130 may be everted under pressure without the need for travel of the drive wheels of

push wires

134, 206, it will be appreciated that the drive wheels may allow for smooth, slow, controlled travel of the balloon, thereby minimizing or avoiding potential perforation of the fallopian tube. The sheath knob 214 may allow the

sheath

162, 212 to be used as an introducer when the

sheath

162, 212 is locked onto the body of the

catheter

126, 210. Sheath knob 214 may be sufficiently compliant to allow a user to move

sheaths

162, 212, e.g., for the pre-extension of the balloon, and move the pre-extension of the balloon into the fallopian tube, if desired. In some embodiments, sheath knob 214 may be tight enough so that accidental balloon or catheter movement may be minimized and/or prevented.

Fig. 26A is a cross-sectional view of the handle portion of fig. 25, and fig. 26B is a detail view of an exemplary embodiment of an internal handle gear mechanism 220 according to the present disclosure. The handle 202 may also have

extension tubes

168, 216, the

extension tubes

168, 216 being attached to a luer fitting 218 in the handle body, e.g., for attaching one or more additional tools or devices, such as an inflation device 172 (see also fig. 23C). A gear mechanism or actuator 220 may be in mechanical communication with the

push wires

134, 206 and may control actuation of the

push wires

134, 206, which in turn may control actuation of the balloon 130 between the everted and inverted positions. In some embodiments, the gear mechanism or actuator 220 may include a plurality of gears that are operative to mesh to have a reduction ratio. According to various embodiments, the handle gear mechanism 220 may include a drive wheel 204, the drive wheel 204 allowing for controlled actuation and single user operation of the gear mechanism 220. A loop "a" as shown in fig. 26A may be included in the handle 202, and the feature for positioning the finger "B" may allow the user to hold the handle 202 in more than one position, and may allow comfortable use of the device regardless of the user's hand size. For example, if the palm of the user's hand is on top of the handle "C", the fingers of the hand may wrap around the inside of the loop "D" for a small hand, or may wrap around the outside of the loop "E" for a large hand.

In some embodiments, the drive wheel 204 may have a square boss that is insertable into the square aperture 222 of the drive gear 224. The drive wheel 204 operable by the health professional may be rotatable such that the square boss may cause the drive gear 224 to rotate. In some embodiments, the drive gear 224 may be rotatable by the drive wheel 204 in the direction indicated by arrow 224A (see fig. 26B). The drive gear 224 may engage the idler gear 226 and the first gear 228, causing these gears to rotate. For example, the first gear 228 may rotate in the direction indicated by arrow 228A, which may be the opposite direction from arrow 224A. Likewise, the idler gear 226 can rotate the second gear 230 in the direction indicated by arrow 230A, and, in response to rotation of the second gear 230, the third gear 232 rotates in the direction indicated by arrow 232A. The push wire 206 can extend between surfaces on and between each of four gears (224, 228, 230, 232) that can each rotate as shown by

arrows

224A, 228A, 230A, 232A in fig. 26B during advancement of the balloon 130 through the push wire 206 (e.g., in a distal direction). In some embodiments, the gear surface may be formed of a material having a high coefficient of friction, such as natural or silicone rubber or polyurethane.

The balloon 130 may be advanced until the proximal ends of the

push wires

134, 206 pass between the drive gear 224 and a first gear 228, which may be mechanically connected to the first gear 228. Once

push wires

134, 206 have passed gear mechanism 220, further rotation of drive wheel 204 does not advance balloon 130 further. Since the tactile indicators of the bladder 130 are fully everted, the user may feel that the

push wires

134, 206 are not present in the

gears

224, 228, 230, 232. By mechanically coupling with the push wire 206, the gear mechanism 220 may allow for a fine, precise and controlled movement of the deployment and/or retraction balloon 130 by eversion and inversion, respectively. As already mentioned, the drive wheel may provide a slow and uniform movement to minimize the possibility of perforation of the fallopian tube, or the inability to navigate through the fallopian tube. The gear mechanism 220 may have a 4 to 1 gear ratio, or a 2 to 1 gear ratio, and it should be understood that any other gear ratio may be used to provide control of balloon travel. The gear ratio may be configured to provide a slow gear rotation. This may ensure that the speed of deployment of the balloon is controlled (e.g., slow and uniform) between users, thereby increasing safety by reducing the risk of adverse events such as perforations.

In some embodiments, to provide feedback to the physician regarding the end of balloon deployment, the internal handle gear mechanism 220 or actuator may include a limiting mechanism on the gear for limiting the travel of the push wire and/or unidirectional balloon movement. In some embodiments, the restraining mechanism may include at least one of a hard stop, a gear jam, a rack and pawl gear, a linear gear, or a drop-key in mechanism. At a predetermined maximum extension, as shown in fig. 26E, the pawl 242 may engage one or more gears (e.g., gears 224, 228, 230, 232) to form a gear jam. Detent 242 may be activated to stop further travel of capsule 130. In some embodiments, the pawl 242 may be any mechanism configured to engage one or more gears. For example, at a predetermined push wire extension, the pawl 242 may rotate about a pivot point to engage one or more gears, causing jamming and preventing further rotation. Alternatively, a rack and pawl gear, linear gear, or a drop-key snap-in mechanism (fig. 26D) may be used to stop the travel of the balloon, and in some embodiments may be provided in the handle (see fig. 26A, detail "F"). Referring to fig. 26C, an exemplary ratchet mechanism for linear motion is shown. Ratchets are mechanisms used to limit motion in one direction. The ratchet may have three main parts: a linear rack and pinion 233, a pawl 235 (e.g., a "dog"), and a base or mount 237. The edge on one side of the teeth 239, 239' on the linear rack may have a steep slope, while the other edge of the rack teeth may have a moderate or gradual slope. For example, the edge on one side of the tooth 239, 239 'may be steeper than the edge on the other side of the tooth 239, 239'. In some embodiments, the steeper slope may have an angle of about 60-90, for example, as shown at 239a, 239a ', while the more moderate slope may have an angle of about 10-50, for example, as shown at 239b, 239 b'. The pawl 235 may contact the linear gear rack 233. When the linear rack is moved linearly in a first direction, the pawl 235 can slide over the teeth 239 without restricting the natural motion of the device. When the direction of motion is reversed to a second direction, the pawl 235 may contact a steep ramp on the gear teeth 239 to impede motion. The pawl 235 may be spring biased downward into the linear rack 233. In some embodiments, a spring, such as a torsion spring, may be provided at pivot point 236, such as at a first end of pawl 235, for pivotable rotation of a second end of pawl 235. In some embodiments, a spring, such as a linear spring, may be disposed at a second end of the pawl 235, as indicated by reference numeral 223, to bias the pawl 235 toward the gear teeth 239. The linear gear rack 233 and the pawl 235 can generally be mounted in fixed relation to one another on a mounting member 237, with the rack sliding relative to the mounting member and the pawl 235 being pivotally connected to the mounting member. In some embodiments, the device may include a manual knob or push button switch to overcome the spring bias on the pawl 235, thereby allowing the pawl 235 to lift from the set of teeth on the linear gear.

Limits may be placed on the ratcheting action of the linear rack and pinion 233 in the gear mechanism 220 of fig. 26A-26B to place limits on the travel of the push wire 206, for example, as shown at "F". During travel of the push wire 206, the pawl 238 can be biased from the linear rack and pinion 233, as shown in detail "F" of fig. 26A. In some embodiments, the pawl 238 can pivot about a point, as indicated by reference numeral 221. A linear rack and pinion 233 may be attached directly to the end of the push wire 206 distal from the balloon 130 in the handle 202. The travel of the push wire 206 may automatically stop when the pawl 238 encounters the stop 243, and the stop 243 may be greater in height than the teeth 239'. A manual knob or push button switch 205 as shown in fig. 25 may be actuated by the user to overcome the spring bias on the pawl 238, thereby allowing the pawl 238 to lift from the linear rack 233 and allow the push wire 206 and attached balloon 130 to retract. In fig. 26D, in another embodiment of a ratcheting action other than linear rack and pinion 233, the push wire 206 may travel continuously and smoothly and wind up on the deployment wheel 245 until the pawl 235 reaches the stop 247 and engages the stop 247 to stop further travel of the balloon 130. In fig. 26E, detent 235 may act as a gear jam when the limit of extension of balloon 130 is reached.

The sequence of steps for accessing and tracking through the fallopian tube can be described using the embodiment of FIG. 23A. When it is desired to pass everted balloon 130 through a length of UTJ (e.g., about 15mm), outer sheath 162 may be placed in apposition with the proximal neck of the fallopian tube, without entering the proximal neck. The outer sheath 162 may support the initial length of the everted balloon 130 until it enters the proximal neck. A portion (e.g., a short length) of the balloon exiting the pressurized everted balloon 130 supporting the outer sheath 162 may have sufficient column strength to be manually advanced through the UTJ, however, the unsupported length (e.g., without the sheath) of the everted balloon 130 may not itself include sufficient stiffness. Thus, without a sheath, an everted/everted balloon 130 may buckle when attempting to travel through the proximal neck and UTJ. In some embodiments, a length of balloon (e.g., 15mm) through the UTJ that can undergo eversion. This initial cannulation length may support the fallopian tubes open, even if spasm occurs, which may occur in this region of the fallopian tubes. It should also be appreciated that other cannula lengths may be used to hold the fallopian tubes open.

In some embodiments, sheath 162 may be compatible with a standard hysteroscope having a working channel (e.g., 5F). Sheath 162 may be used as a balance in an exemplary system to provide a wall thickness large enough to give the sheath sufficient column strength, and thin enough to keep the inner diameter of the sheath large enough to accommodate balloon 130. Such balancing may improve cell collection efficiency, for example, by having an inner diameter sufficient to retain the capsule 130 without inadvertently removing (scraping) cells from the capsule surface. It should be appreciated that the balloon 130 may be retained within the sheath 162 in an inflated state and/or a deflated state.

As already mentioned, a sheath knob 164 or male luer lock fitting of the connector including the Tuohy-Borst seal 136 may be included at the proximal end of the sheath 162. A Tuohy-Borst adapter including a seal 136 is a medical device used to form a seal between devices and to attach a catheter to other devices. The Tuohy-Borst seal 136 may be tightened to slip fit a catheter or cannula that holds the sheath 162 in place. The sheath knob 164 may mate with a female luer lock fitting (if any) at the instrument port on the working channel of the hysteroscope 20. Referring again to fig. 3, a male luer lock or sheath knob 164 may be connected to the instrument port 23 so that the catheter 126 and/or sheath 162 may move with the hysteroscope 20. In some embodiments, the instrument port 23 may further include a seal for the conduit 126 to extend through. When these respective luer fittings are connected, the tip of sheath 162 may protrude beyond the distal end of the hysteroscope, for example by about 2-3 cm. The sheath 162 may also protect a portion (e.g., a length of about 1.5cm) of the everted balloon 130 from damage during device preparation as the catheter 126 travels through the working channel of the hysteroscope. A stainless steel tube, such as hypotube 138, may be at least a portion of the inner cannula 126 to provide sufficient rigidity and/or column strength to minimize or prevent kinking of the portion protruding from the proximal end of the hysteroscope working channel. In some embodiments, hypotube 138 may be sized to have an outer diameter of approximately 0.050 "by 0.004" wall thickness to achieve sufficient stiffness.

In some embodiments, hypotube 138 may ensure that handle 202 is not disturbed or disengaged from the working channel of hysteroscope 20 when the medical professional releases the device during the surgical procedure. The sheath 162 may be coaxial with the tube or catheter 126 and may be slidably adjustable to cover at least a first length of the balloon extending outwardly from the distal end in the everted position. The sheath 162 may form a physical barrier and may protect the balloon in at least one of the everted, partially everted, and/or fully everted positions and may serve to protect the collected cells from dislodgement during transport out of the patient's body.

As already mentioned, at least a portion of each of the sheath 162, the tube or catheter 126, and/or the balloon 130 may be translucent, optically transparent, or a combination thereof to facilitate visual feedback of the relative positions of the device components described above during deployment and retraction. It should be understood that the hysteroscope 20 may be well suited for visual observation of the cell collection with the device. The translucency and/or transparency of the device components may depend on the wavelength of observation. For example, thermoplastic materials appear clear under visible light, but are opaque to other portions of the electromagnetic spectrum.

Fig. 23C shows the balloon-tip catheter 160 of fig. 23A (with a tube reservoir or extension tube 168) and an inflation device 172 according to an exemplary embodiment of the present disclosure. It should be appreciated that in some embodiments, the extension tube 168 may be similar to the extension tube 216 as shown in FIG. 26A. The

extension pipes

168, 216 may be configured to withstand pressurization. Pressurization of bladder 130 by fluid injection may be performed using an injector device, such as exemplary inflation device 172. Rotation of the threaded plunger shaft by the releasable lock may increase and maintain pressure in the expander 172, while the pressure gauge 174 provided with the expander 172 may allow control of the input pressure. In some embodiments, balloon tip catheter 160 may provide for single person operation of the device. A length of pressure or

extension tubing

168, 216 may be added between the inflation device 172 and the inflation port 166 on the device. The

extension tubes

168, 216 may be constructed of a polymer such as polyurethane or polyvinyl chloride (PVC), with or without polymer or metal coils or braided reinforcements. The

extension tubes

168, 216 may contain some amount of inherent elasticity, while the everting bladders may be generally inelastic. When the bladder 130 is fully pressurized, the

extension tubes

168, 216 may impart fluid capacity to the system. A small volume of fluid may be contained in the everted bladder and this volume may be further reduced by the volume occupied by push rod 134 (e.g., when the bladder is everted, push rod 134 moves into bladder 130). The resulting everted balloon volume may be smaller compared to the larger volume in pressure tube 168, which may allow balloon 130 to evert to its full length without significantly reducing pressure once balloon tip catheter 160 is pressurized.

In response to positioning the stopcock 170 near or away from the device and hysteroscope 20, a length of

extension tubing

168, 216 may be added between the inflation port 166 on the device and the inflation device 172. For example, as shown in FIG. 25, luer 218 may connect

pressure tubing

168, 216 for connection with stopcock 170. In some embodiments, a stopcock 170 may be provided at the end of the

extension tubes

168, 216 for connection with the luer 219 and the inflation device 172. In some embodiments, stopcock 170 may be connected to luer fitting 218. Stopcock 170 may be closed after pressurization and inflation device 172 may be removed from the examination region prior to insertion and eversion of balloon 130. Such a single operator procedure may be less cumbersome and more efficient in a medical procedure. It should also be appreciated that in some embodiments, the luer fitting 219 may be connected to the inflation device 172 without the stopcock 170.

As described above with reference to fig. 23A-23C, the everting balloon 130 may extend a total distance of about 7cm distal to the catheter tip in order to traverse the entire length of the fallopian tube. As everting balloon 130 exits the catheter tip, everting balloon 130 may form a curved shape at end 130a, and the everted portion may comprise a double-walled construction. The curved shape may be an atraumatic shape for minimizing or avoiding damage during extension into the fallopian tube. Thus, for example, the push rod 134 travels forward a distance of about 14cm to produce an everted capsule length of 7 cm. This length of push rod may initially extend rearwardly from the proximal end of the catheter 126, directly into the operator's face, making it cumbersome to use. The pushrod may also be susceptible to contamination from the sterile device due to its length, as it may extend into the surgeon's workspace during the surgical procedure. For example, the proximal end of the long pushrod 134 may contact the face of a surgeon or surgical mask during use. Accordingly, it may be desirable to provide a putter system that does not necessarily extend the full length of the putter 134 rearwardly. The superelastic pushrod 175 and carrier design of fig. 24 and the balloon-tip catheter 200 of fig. 25 configured with the handle 202 may include a pushrod and minimize and/or avoid the need to extend the pushrod back toward the user.

Fig. 27 shows a side cross-sectional view of an exemplary everted balloon tip catheter 180 according to the present disclosure including a tube 182 of smaller diameter than the expanded diameter of everted balloon 130 for insertion into a UTJ of a patient. Tube 182 may straighten a portion of balloon tip 163. In some embodiments, the tube 182 may extend distally away from the tip of the cannula. In some embodiments, tube 182 may have a wall thickness of about 0.0005 "-0.001" (e.g., be a "thin-walled" tube) and may extend about 1.5cm distally of the cannula tip. Tube 182 may have sufficient thickness and resiliency to support balloon 130 to maintain the position of balloon tip 163 (e.g., maintain a straight position). In some embodiments, the diameter of tube 182 may be smaller than the diameter of balloon 130, such that balloon 130 may remain flexible and compressible. Such flexibility may be advantageous in allowing balloon 130 to travel through the UTJ. In some embodiments, balloon 130 may include a tube 182 to support and/or straighten the balloon. In some embodiments, the tube 182 may have an outer diameter x0.001 "of 0.033" and a wall x1.5 cm long.

Fig. 28 shows a side cross-sectional view of an everted balloon tip catheter 190 that includes one or more flexible polymer monofilament strings and/or sutures 192 as an extension attached to the distal end of the cannula or catheter 126. According to an embodiment of the present disclosure, the strands 192 may extend into the everting balloon tip 163, thereby supporting and keeping the tip straight for insertion into the UTJ of the patient. In some embodiments, the one or more flexible polymeric monofilament strings and/or sutures 192 may extend into the balloon tip 163 (e.g., about 1.5 cm). The monofilaments 192 can be formed of nylon, polypropylene, or other flexible polymeric material, or a combination thereof. The monofilament strands may have a diameter of about 0.006 "-0.012". In some embodiments, balloon 130 may have an outer diameter of about 0.033 "(0.8 mm) with monofilament 192 having a 0.008" diameter within an everted balloon end of about 1.5cm in length.

Fig. 29A-29C illustrate a steerable balloon tip 252 of a balloon catheter 250 for eversion using a guidewire according to an exemplary embodiment of the present disclosure. As shown in fig. 29A, the steerable balloon tip 252 may be controlled by a right directional guidewire 254 and a left directional guidewire 256. In fig. 29B, the right guidewire 254 can be manipulated (e.g., pulled, as indicated by arrow 255) to steer the balloon tip 252 to the right. Conversely, in fig. 29C, the left guidewire 256 can be manipulated (e.g., pulled, as indicated by arrow 257) to manipulate the balloon tip 252 to the left. It should be noted that in addition to the movement in the X-Y plane achieved with a pair of guide wires as shown, additional guide wires may be included to provide movement in the Z plane.

Fig. 30 illustrates a side perspective view of a balloon catheter 260 having a smaller diameter guiding balloon tip 262 at the distal end of an everted balloon 130, according to an exemplary embodiment of the present disclosure. The smaller diameter guiding balloon tip 262 may be sized to gradually expand the opening at the constriction of the UTJ while being flexible by the blunt edge so as not to perforate the wall at the UTJ.

Fig. 31 illustrates a side perspective view of a balloon catheter 270 having a flexible guidewire 272 on the tip of the balloon 30 according to an exemplary embodiment of the present disclosure. The flexible guidewire may guide the balloon catheter 220 through the UTJ into the fallopian tube.

In some embodiments, a portion of the everted balloon may be treated with a coating of a fluoropolymer, silicone, or like material, or a combination thereof, that lubricates the surface at the guiding portion of the balloon catheter, which may enter the constricted portion of the fallopian tube (e.g., UTJ).

Fig. 32 illustrates a partial side perspective view of the ribbon balloon 130S of fig. 32 prior to inversion of the ribbon balloon 130S into a catheter or cannula according to an embodiment of the present disclosure. Indicia 131 on the balloon provide a visual feedback indication of the progress of balloon eversion. In particular embodiments, indicia 131 may be about 1mm wide and spaced at about 1cm increments along the entire length of balloon 130S. Alternate spacing of the strips on the balloon or other visual indicia may be spaced closer together to obtain finer position feedback, or further apart to obtain coarser feedback. Other visual indicia of eversion length may include a sinusoidal marking having a known period length. It should also be understood that the length indicator may also comprise segments of known length of different colors.

Fig. 33 illustrates a side cross-sectional view of a balloon tip catheter 280 configured with a banded balloon 130S according to an exemplary embodiment of the present disclosure. As shown in fig. 33, indicia 131 of the strip eversion balloon 130S may be coupled with a transparent distal section 167 of the cannula or catheter 126 to provide visual feedback of the balloon eversion. In some embodiments, the indicia may be pad printed or scribed with a highly visible color of non-erasable indicia. In some embodiments, indicia 131 may be about 1mm wide, spaced at about 0.5cm increments along the entire length of the balloon. Pad printing (also known as overprinting) is a printing process that transfers two-dimensional images onto three-dimensional objects. Other patterns may be used in place of or in addition to markings 131 on the surface of bladder 130S. For example, the markings 131 on the capsules 130S may be spaced apart (e.g., about 0.5cm), and dots may also be added in the remaining spaces between the markings 131. Each marker 131 entering the field of view in the transparent distal segment 167 can indicate the length of successful eversion of the balloon 130S (e.g., 0.25cm, since the length traveled by the pushrod is approximately twice the corresponding approximate length of balloon eversion (e.g., 0.5 cm)). Different thicknesses of the indicia 131, as well as different colors of indicia, or different numbers of indicia, or combinations thereof, may be used in the same manner as described for the stripe and dot combinations. In some embodiments, a color-coded section may be added to balloon 130S to indicate the degree of balloon eversion.

Additional embodiments of feedback markers (which may be externally visible to a physician outside the patient's body) are used to correct the degree of balloon eversion. In some embodiments, knotted strings or braided sutures as extensions may be adhered to the distal end of the push rod or the tip of the balloon and may be spaced at known increments to provide tactile feedback regarding the progress of balloon eversion. Knotted strings or braided sutures may allow visualization of the advancing motion of the balloon when it is everted. The knotted string or suture may be radiopaque. The string may have a color-coded region for providing visual feedback to the operator. To enhance visualization of the knotted string or braided suture, the suture, logo or color coding region may be provided in a color that is highly contrasting with the catheter and anatomical structure. In some embodiments, the braided surface of the suture may facilitate the collection and/or retention of cells due to the texture and folds of the braid. For example, tissue and/or cells may be embedded in the texture and/or folds of the braid. In some embodiments shown in fig. 34A, string 140 may be pad printed with indicia 131 in a manner similar to the bladders indicated above in fig. 32 and 33. Fig. 34B shows a string 140' having a series of knots or sutures 142. The balloon 130 may be at least partially transparent to enhance visualization of the string, logo, knot or suture.

In some embodiments, the string as an extension may be braided as shown in fig. 11C and 11D. Braided strings, knots or sutures may also provide additional cell collection surfaces. In some embodiments, cells may be collected and retained within the braid of the suture 43, which may be advantageous over cells collected only on the suture surface. Cells trapped within the braid of suture 43 may be less likely to be inadvertently removed or wiped away during retraction of suture 43 and/or balloon 32, as cells may be trapped between the braids, thereby providing protection for the trapped cells.

In some embodiments, as shown in fig. 11E and 11F, different strands of string or suture may be formed of different colors, tones, or thicknesses relative to other strands. For example, as shown in the three-ply suture in fig. 11E,

strands

47 and 49 of suture 46 may be a different color or a darker shade than strand 51. Alternatively, as shown in fig. 11F, strands 47 'and 51' of suture thread 46 'may be a different color or lighter shade than strand 49'. Strands 47, 47', 49', 51' may be formed of selected colors along the entire length such that when in a braided pattern, a medical professional can visualize color contrast or differentiation along the braided length at predetermined segment lengths. For example, per third portion, first strands 47, 47' may extend a length L1, L1' on an outer portion of suture 46, 46' (e.g., braided), per third portion, second strands 49, 49' may extend a length L2, L2' on an outer portion of suture 46, 46', and per third portion, third strands 51, 51' may extend a length L3, L3' on an outer portion of suture 46, 46 '. The strands are shown as having the same thickness for visual clarity, but it should be understood that the strings, knots, sutures may be of any thickness, and may be of equal thickness or of different thicknesses. In other embodiments, the fibers within a given strand may have a color difference relative to the rest of the strand.

An advantage of varying the appearance of the strands along the length of the suture 46, 46' is that the appearance of the strings or sutures can be varied along the length, providing feedback to the operator that the respective string or suture is moving and the balloon is everting. For example, a medical professional can visualize the movement of the suture thread by color contrast of the suture thread 46, 46'. The string or suture may also be treated with a surface modification, such as plasma, corona or nanofiber surface application, to alter its surface properties. Furthermore, the braided, knotted or sutures may also provide additional tensile strength to the balloon, as the strings or sutures may act to absorb and dissipate forces acting on the balloon, thereby reducing the risk of balloon detachment.

Additional feedback mechanisms may include filling the balloon 130 with agitated saline and visualizing the bubbles with ultrasound, and sinusoidal patterns for the balloon, where the distance between the maxima of the sine wave defines the incremental distance of balloon eversion.

Navigation within the fallopian tube and indication of a clear path or obstruction may be provided by the release of microbubbles from the end of the balloon or the distal end of the tube from which the balloon everts. The travel of the microbubbles can be tracked using imaging (such as ultrasound) to determine where an open path exists. In the case of an obstruction 251, such as an occlusion or constriction, the microbubbles can clump or aggregate when the microbubbles are obstructed. In response to detecting a set of microbubbles, the medical professional can determine an occlusion. Fig. 36A shows the release of a series of microbubbles 249 from the end of the balloon 130 in the fallopian tube 1, where there is no constriction or obstruction, as shown by the stable continuous line of microbubbles 249. In some embodiments, microbubbles may be delivered through the inner lumen 54 of the balloon, as shown in fig. 17A-17B. The frequency or spacing of the microbubbles 249 can be controlled to make finer measurements than with an air source that is modulated on or off, wherein air is introduced into the fluid injected into the bladder 130. Figure 36B shows a fallopian tube 1 with a tubular constriction or obstruction 251 in which the tubular constriction or obstruction 251 would obstruct the flow of microbubbles 249 and the microbubbles 249 begin to aggregate or bunch up at the point of the constriction or obstruction 251. The accumulation of microbubbles 249 can provide a visual indication to the user of the location of the constriction or obstruction 251 in the fallopian tube 1. In response to the detected occlusion 251, the medical professional may perform additional imaging, such as ultrasound, to determine where the balloon has stopped.

The present disclosure further provides various methods of collecting cells from a lumen of a subject using embodiments of the catheters described above. These methods may include: using a catheter comprising at least a tube, a balloon (with or without an extension) fixed to a distal end of the tube, a push wire actuating the balloon within the tube between an everted position and an everted position extending beyond the distal end, and a slidable sheath coaxial with the tube; everting a first portion of the balloon (about 1 to 2cm, according to some embodiments) distally beyond the distal end of the tube to a preselected distance; positioning the sheath and the everted first portion of the balloon adjacent to a lumen of a subject; or a combination thereof.

The balloon may be inflated or otherwise pressurized to cause initial eversion of the balloon. For example, by pressurizing the balloon, the balloon may be provided with column strength, allowing it to evert as the push wire travels. The sheath knob may travel to a first marker on the hypotube and/or the catheter. The balloon may evert to a point at the distal tip of the sheath. The distal tip of the sheath and the pre-extended balloon may be placed near the ostium of the fallopian tube. The sheath may be held in place by holding the sheath knob in a selected position, and the balloon and catheter may be further advanced so that an initial portion of the everted balloon is inserted into the proximal neck.

The health professional may rotate the drive wheel to further evert the suture and/or balloon as an extension. The drive wheel may be rotated until the balloon and/or suture is partially or fully everted. In some embodiments, the final everted length (e.g., about 7-12cm) may be about equal to half the push wire travel. When the balloon and/or suture is fully everted, the distal end of the push wire may remain in the catheter and may not contact the fallopian tube.

A balloon that is fully everted within the fallopian tube can fill the potential space within the fallopian tube, thereby contacting the inner surface of the fallopian tube. Surface area contact can transfer cells to the surface of the capsule. When everted in the fallopian tube, the balloon may contract such that the folds in the balloon surface may capture cells collected on the balloon surface. In some embodiments, the balloon may cycle between inflation and deflation while everting for potentially increasing cell collection on the balloon surface and within balloon surface features. In some embodiments, the suture may extend from the balloon fully everted, further collecting cells on the suture.

When collection of cells on the balloon surface and/or suture is complete, the medical professional can retract the handle of the device while holding the sheath in place so that the everted balloon and/or suture can be retracted within the sheath. When aligned with the sheath knob, a marking on the tube of the catheter may provide an indication that the full length of the balloon/extension has been retracted with the sheath. The sheath may protect cells collected on the surface of the balloon and/or on the suture for removal of the device from the working channel of the hysteroscope.

Cells may be collected on the balloon by inserting the everted first portion of the balloon into the lumen and further everting the balloon into the lumen using a push wire. Some embodiments of the method may further comprise adjusting the speed of the further everting step relative to the inserting the everted first portion of the balloon into the lumen step. When aligned with the sheath knob, the markings on the catheter tube may provide an indication that the full length of the balloon/extension has been retracted with the sheath.

Any patents or publications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. The foregoing description is illustrative of particular embodiments of the present disclosure, but is not meant to be limiting in its practice.

Numerous specific details have been set forth herein to provide a thorough understanding of the embodiments. However, it will be understood by those skilled in the art that the embodiments may be practiced without these specific details. In other instances, well-known operations, components and circuits have not been described in detail so as not to obscure the embodiments. It can be appreciated that the specific structural and functional details disclosed herein may be representative and do not necessarily limit the scope of the embodiments.

Some embodiments may be described using the expression "coupled" and "connected" along with their derivatives. These terms are not intended as synonyms for each other. For example, some embodiments may be described using the terms "connected" and/or "coupled" to indicate that two or more elements are in direct physical or electrical contact with each other. However, the term "coupled" may also mean that two or more elements are not in direct contact with each other, but yet still co-operate or interact with each other.

It should be noted that the methods described herein need not be performed in the order described or in any particular order. Additionally, various activities described with respect to the methods described herein can be executed in serial or parallel fashion.

Claims

1. A device for fallopian tube diagnosis, comprising:

a tube having a distal end;

a balloon having a first end coupled to the distal end of the tube, the balloon being disposed in the tube in a first everted position and being movable to a second everted position, extendable a distance distally of the distal end of the tube such that a surface of the balloon is contactable with an inner surface of a fallopian tube; and

a push wire having a distal end coupled to a second end of a balloon, wherein the balloon is movable from the first everted position to the second everted position by actuation of the push wire;

wherein a surface of the balloon comprises a plurality of surface features for collection, retention, or both of a tissue sample of an interior surface of a fallopian tube; and is

Wherein the capsule is etched or embossed to impart the plurality of surface features, wherein the plurality of surface features comprise micro-ridges having a peak to valley height of 0.1 to 500 microns, wherein the plurality of surface features comprise micro-ridges that are orthogonal to an axis of the capsule, or wherein the plurality of surface features comprise micro-ridges having a peak to valley height of 0.1 to 500 microns and that are orthogonal to an axis of the capsule.

2. The device of claim 1, wherein the surface features comprise a plurality of wrinkles formed in a surface of the balloon.

3. The device of claim 2, wherein the plurality of folds in the balloon surface are formed in the balloon surface and are configured to retain at least a portion of the tissue sample after contacting an inner surface of the fallopian tube.

4. The device of any one of claims 1-3, wherein the surface features are etched on a surface of the capsule.

5. The device of any one of claims 1-3, wherein a portion of the surface of the balloon is embossed to form a plurality of peaks and valleys.

6. The device of any one of claims 1-3, wherein the plurality of surface features improve adhesion of the tissue sample to the balloon surface compared to a balloon surface without the surface features.

7. The device of any one of claims 1-3, wherein the balloon is inflatable for moving the balloon from the first everted position to the second everted position.

8. The device of any one of claims 1-3, further comprising a filament attached to a distal end of the push wire, wherein the filament is disposed within the balloon in a first everted position and the filament is extendable from the balloon in a second everted position.

9. A system for collecting a tissue sample within a body lumen, comprising:

a tube having a distal end and a balloon having a first end coupled to the distal end of the tube and a second end coupled to the distal end of the push wire, the balloon being positionable in a first everted state;

wherein the push wire is configured to travel to evert the balloon to a second everted state such that the balloon extends out of the distal end of the tube;

wherein a surface of the balloon is configured to contact an inner surface of a body lumen in a second everted state for transferring a tissue sample to the balloon surface;

wherein the balloon surface comprises a plurality of surface features for collection, retention, or both of a tissue sample; and is

10. The system of claim 9, wherein the surface feature comprises a plurality of wrinkles formed in the surface of the balloon.

11. The system of claim 10, wherein the plurality of folds in the balloon surface are configured to retain at least a portion of a tissue sample after contacting an inner surface of a body lumen.

12. The system of any of claims 9-11, wherein the surface features are etched on a surface of the capsule.

13. The system of any of claims 9-11, wherein the plurality of surface features improve adhesion of the tissue sample to the balloon surface compared to a balloon surface without the surface features.

14. The device of any of claims 1-3, wherein the plurality of surface features comprise micro-ridges having a peak to valley height of 0.1 to 500 microns and orthogonal to the axis of the balloon.

15. The system of any of claims 9-11, wherein the plurality of surface features comprise micro-ridges having a peak to valley height of 0.1 to 500 microns and orthogonal to an axis of the balloon.