CN114391887B

CN114391887B - systems, methods, and devices for fallopian tube diagnostics

Info

Publication number: CN114391887B
Application number: CN202210050289.2A
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: 2024-03-26
Anticipated expiration: 2038-08-16
Also published as: JP2020530364A; EP3668584A1; CN110997053B; AU2018319532A1; CA3070679A1; WO2019040094A1; JP7093404B2; CN110997053A; AU2018319532B2; CN114391887A

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 balloon may be disposed in the tube in a first everted position and movable to a second everted position. The balloon may be extendable distally of the distal end of the tube a distance such that a surface of the balloon may contact an inner surface of the fallopian tube. The push wire may have a distal end coupled to the second end of the balloon. By actuating the push wire, the balloon may be moved from a first everted position to a second everted position. The surface of the balloon may include a plurality of surface features for collecting a tissue sample of the interior surface of the fallopian tube.

Description

systems, methods, and devices for fallopian tube diagnostics

The application is a divisional application of China patent application with the application date of 2018, 8-16, the national application number of 201880052679.5 (PCT application number of PCT/US 2018/000229) and the name of 'system, method and device for oviduct diagnosis'.

Cross Reference to Related Applications

The present application is a continuation-in-part application of U.S. patent application Ser. No. 15/053,568, entitled "Methods and Devices for Fallopian Tube Diagnostics", filed 25/2016, and claims priority thereto, and a continuation-in-part application of U.S. patent application Ser. No. 14/764,710, entitled "Methods and Devices for Fallopian Tube Diagnostics", filed 30/2015, and national phase application of International patent application Ser. No. PCT/US2014/014472, entitled "Methods and Devices for Fallopian Tube Diagnostics", filed 2/3/2014, and claims priority to U.S. provisional patent application Ser. No. 61/873,753, entitled "Everting Catheter for Fallopian Tube Diagnostics", filed 9/4/2013, and U.S. provisional patent application Ser. No. 61/759,783, entitled "Methods and Devices for Fallopian Tube Diagnostics", filed 2/1/2013, the entire disclosures of which are expressly incorporated herein by reference.

The present application is a non-provisional application, U.S. provisional application serial No. 62/546,791 entitled "Devices for Fallopian Tube Diagnostics" filed 8/17/2017 and U.S. provisional application serial No. 62/660,512 entitled "Methods and Devices for Fallopian Tube Diagnostics" filed 4/2018, the disclosures of which are expressly incorporated herein by reference in their entireties, and claims priority thereto.

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 a body lumen (including a fallopian tube).

Background

Ovarian cancer is a major disease in women, and 1 out of 72 women in the united states may be diagnosed with this disease during her lifetime. In 2012, over 22,000 women were diagnosed with ovarian cancer in the united states. Due to the lack of an effective screening test, early detection of ovarian cancer may be difficult, making it impossible to diagnose ovarian cancer until the disease has progressed to an advanced stage, thereby limiting treatment options.

Screening for ovarian cancer may typically involve surgery to obtain a sample of cells for diagnosis. For example, since the ovary is intra-abdominal, it is possible to perform laparoscopic or open surgery (laparotomy) to access the ovary. Any surgical procedure increases the risk to the patient, including but not limited to adverse reactions and/or requiring significant recovery time. Furthermore, an ovarian biopsy may expose the patient to additional risk of potentially spreading diseased (e.g., cancerous) cells.

Thus, there is a need for devices and methods that allow samples to be taken from the fallopian tubes for assessing ovarian cancer in a less invasive and controlled manner, and particularly without the need for skin incisions. There is a further need to obtain a representative cell sample from the fallopian tube using a catheter to screen for early stage cancer.

with these and other considerations in mind, 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 example 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, movable to a second everted position, and extendable a distance distal of the distal end of the tube such that a surface of the balloon may contact an inner surface of the fallopian tube. The push wire may have a distal end coupled to the second end of the balloon. By actuating the push wire, the balloon may be moved from a first everted position to a second everted position. 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 pleats formed in the surface of the bladder, and may have at least one of a plurality of edges, micro-ridges, or overlapping materials, or a combination thereof. A plurality of pleats may be formed in the balloon surface. 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 the inner surface of the fallopian tube. Surface features may be etched into the surface of the capsule. A portion of the balloon surface may be embossed to form a plurality of peaks and valleys. The plurality of surface features may enhance adhesion of the tissue sample to the surface of the capsule as compared to a surface of the capsule without the surface features. The balloon may be inflatable for moving the balloon from a first everted position to a second everted position. The filaments may be attached to the push wire, the filaments may be disposed within the balloon in a first everted position, and the filaments may extend from the balloon in a second everted position.

In accordance with 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 balloon may be positioned in a first everted state. The push wire may be configured to advance 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 pleats formed in the balloon surface, the pleats having at least one of a plurality of edges, micro-ridges, or overlapping materials, or a combination thereof. A plurality of pleats may be formed in the balloon surface. The plurality of folds in the balloon surface may be configured to retain at least a portion of the tissue sample after contacting the inner surface of the body lumen. Surface features may be etched on the surface of the capsule. The plurality of surface features may enhance adhesion of the tissue sample to the surface of the capsule as compared to a surface of the capsule without the surface features.

According to an exemplary 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 balloon 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 pleats formed in the surface of the bladder, and may have at least one of a plurality of edges, micro-ridges, or overlapping materials, or a combination thereof. A plurality of pleats may be formed in the balloon surface. The plurality of folds in the balloon surface may be configured to retain at least a portion of the tissue sample after contacting the inner surface of the body lumen. The plurality of surface features may enhance adhesion of the tissue sample to the surface of the capsule as compared to a surface of the capsule without the surface features.

According to an example 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 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 balloon in a first everted position and may extend from the second end of the balloon in a second everted position.

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

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 balloon and the extension 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 in 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 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 the 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 a first everted position to a second everted position.

In accordance with example 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 as the balloon moves from the first everted position to the second everted position into the fallopian tube. The sheath may minimize balloon collapse when the balloon is everted into the fallopian tube. The sheath may protect the everting balloon or extension, or both, after removal of the cell collection 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 tube.

In accordance with example embodiments of the present disclosure, devices, systems, and methods for fallopian tube diagnosis may include one or more markers for visualization. The first marker 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 the positioning of the sheath relative to the tube as a preparatory step to covering at least a portion of the balloon in the second everted position. The first marker 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 in the second everted position, the sheath may be moved in a proximal direction to expose at least a portion of the balloon. A second marker may be disposed on the tube and may indicate the 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 covering 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 the distal end of the tube relative to the junction of the balloon and the tube. The third marker may visually indicate the end of the fallopian tube to confirm the extension or positioning of the balloon and/or extension portion in the fallopian tube. The one or more indicia may be formed as score lines, coating substances or strips of material, or a combination thereof. The one or more markers may improve or normalize the positioning and extension of the balloon into the fallopian tube. A seal may be disposed around 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 the first everted position and the second everted position. In response to leakage formation 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 example embodiments of the present disclosure, devices, systems, and methods for fallopian tube diagnosis may include that at least a portion of the sheath may be translucent, transparent, or otherwise transparent. At least a portion of the tube may be translucent, transparent, or otherwise see-through. At least a portion of the balloon may be translucent, transparent, or otherwise see-through. The tube may include a transparent portion and an opaque portion. The opaque portion may be disposed 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 balloon and may be disposed within the balloon in a first everted position and may extend from the balloon 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 with a fluid that is opaque, or visible or detectable for visualization, to move from a first everted position to a second everted position.

In accordance with example embodiments of the present disclosure, devices, systems, and methods for fallopian tube diagnostics may 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 include a reduction ratio for additional control of the movement of the bladder. The drive wheel and gear mechanism may provide for 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 toward the rack and pinion. The pawl may engage with 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 a first side and a more moderate slope on a 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 is labeled in every drawing, nor is every component of each embodiment 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 a uterus to an ovary, with a uterotubal junction (UTJ);

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 according to the present disclosure;

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

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

FIG. 6A illustrates a cross-sectional view of an exemplary embodiment of an everting capsule (having an externally configured sleeve, and in a contracted state) according to the present disclosure;

FIG. 6B illustrates a cross-sectional view of an everting bladder (having the outer construction sleeve of FIG. 6A, and in an inflated state) according to the present disclosure;

FIG. 6C illustrates an exemplary embodiment of inflation of an everting balloon having the outer construction sleeve of FIGS. 6A-6B;

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

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

FIG. 7C illustrates an exemplary embodiment of inflation of an everting sleeve and elastic balloon with the inelastic delivery balloon of FIGS. 7A-7B;

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

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

fig. 9A shows a cross-sectional view of an exemplary embodiment of an everting balloon catheter according to the present disclosure, in a contracted state;

FIG. 9B illustrates a cross-sectional view of the everting balloon catheter of FIG. 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;

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

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

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

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

11C-11D illustrate cross-sectional views of exemplary embodiments of everting balloon catheters according to the present disclosure;

FIGS. 11E-11F illustrate cross-sectional views of exemplary embodiments of everting balloon catheters according to the present disclosure;

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

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

fig. 13A shows a cross-sectional view of an exemplary embodiment of an everting balloon catheter in a contracted state according to the present disclosure;

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

fig. 14A shows a cross-sectional view of another exemplary embodiment of an everting balloon catheter in a contracted state according to the present disclosure;

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

Fig. 15A shows a cross-sectional view of an exemplary embodiment of an everting balloon spiral cannula in a contracted state according to the present disclosure;

FIG. 15B illustrates the everting balloon spiral cannula of FIG. 15A in an inflated state according to the present disclosure;

FIG. 16A illustrates a cross-sectional view of an exemplary embodiment of an everting distal arcuate balloon cannula in a contracted state according to the present disclosure;

FIG. 16B illustrates the everting distal arc-shaped balloon cannula of FIG. 16A in an inflated state according to the present disclosure;

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

FIG. 17B illustrates the everting balloon catheter of FIG. 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 illustrates an exemplary embodiment of an extension portion in a retracted state after cell collection according to the present disclosure;

FIG. 20 illustrates the individual extensions of FIG. 19 in a deployed state according to the present disclosure;

fig. 21A illustrates a side cross-sectional view of an exemplary embodiment of a balloon catheter with a balloon tip everted prior to balloon deployment according to the present disclosure;

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

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

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

FIG. 23B illustrates the balloon end catheter of FIG. 23A according to the present disclosure;

FIG. 23C illustrates the balloon end catheter of FIG. 23A according to the present disclosure;

FIG. 24 illustrates a side cross-sectional view of an exemplary embodiment of a balloon tip catheter according to the present disclosure;

FIG. 25 illustrates a side view of an exemplary embodiment of a balloon tip catheter according to the present disclosure;

FIG. 26A illustrates 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 a 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 pinion ratchet assembly in accordance with the present disclosure;

FIG. 26D illustrates a side view of an exemplary embodiment of a drop key snap-in of the linear rack 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 illustrates a side cross-sectional view of an exemplary embodiment of a balloon tip catheter according to the present disclosure;

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

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 illustrates a side perspective view of an exemplary embodiment of a balloon catheter and guide balloon tip according to the present disclosure;

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

FIG. 32 illustrates an exemplary embodiment of a balloon prior to everting the balloon into a catheter according to the present disclosure;

FIG. 33 illustrates a side cross-sectional view of an exemplary embodiment of a balloon end catheter having the balloon and sheath of FIG. 32 inverted according to the present disclosure;

FIG. 34A illustrates 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 illustrates 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;

FIG. 35 illustrates eversion of an exemplary embodiment of a balloon according to the present disclosure;

FIG. 36A shows a cross-sectional view of an exemplary embodiment of a balloon according to the present disclosure; and

Fig. 36B shows a cross-sectional view of an exemplary embodiment of a balloon 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 be limiting beyond the scope of 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 pertains.

Where a range of values is provided, it is understood that an intermediate value between the upper and lower limits of the range up to one tenth of the unit of the lower limit is 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, step 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 described above, challenges to effectively detecting early cancers in women (e.g., ovarian cancer) may include taking biopsy samples without surgery. Anatomically, the ovary is very close to the umbrella in the region of the distal opening or neck of the fallopian tube. Ovaries released from the ovaries can be collected by the umbrellas and delivered to the uterus through the fallopian tubes. For ovarian cancer, cells may deposit in the fallopian tube and eventually may migrate into the uterus. Cell samples obtained from the uterus can detect ovarian malignancy; however, the incidence of migration of ovarian cancer cells to the uterus may be too low to make uterine sampling a reliable diagnostic test for ovarian malignancy.

More cancer cells may migrate to or originate from the fallopian tube, which may concentrate at the distal portion of the fallopian tube near the distal cervical opening. The ability to detect cells in the fallopian tube for malignancy may be of clinical value for early detection and treatment of such cancers. It should be appreciated that an early detection screen may be performed that detects migrating cancer cells.

The fallopian tubes are extremely fragile and are easily perforated during medical procedures. Thus, it may be difficult to safely introduce a diagnostic device into the fallopian tube with known devices. Referring now to fig. 1, a patient's fallopian tube 1 may extend from a proximal cervical os 3 (connected at a utero-tubal junction (UTJ) 2) near the uterus to a distal cervical os 5 and to an ovary 6. Perforation may occur at UTJ 2, which is a constriction occurring 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 proximal neck finish 3. In some patients, the body 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 UTJ may be about 1mm.

According to an exemplary embodiment, 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 harvesting such cells in a less invasive surgical procedure that, in some embodiments, occurs without a skin incision. Although described in relation to sample collection and diagnosis of fallopian tubes, it should be understood that the systems and methods of sample collection and diagnosis may be applied to any other body lumen, tube, and delivery tube, including, but not limited to, bile ducts, hepatic ducts, cholecyst ducts, pancreatic ducts, lymphatic ducts, and circulatory vessels in accordance with the present disclosure.

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

Exemplary embodiments of catheters for fallopian tube diagnosis for minimally invasive surgery may include any of the following: (1) A proximal cervical opening to the 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 advance into the fallopian tube. The inflation balloon at the end of the second catheter may travel through the proximal portion of the fallopian tube and may be everted further into the fallopian tube; (4) The balloon may contact the luminal inner surface of the fallopian tube and the cells may be removed for sampling; and/or (5) the capsules may be removed and inserted into vials for cell collection and subsequent processing.

An embodiment of an exemplary catheter may be configured for insertion into a fallopian tube (see fig. 1). The fallopian tube has curvature (e.g., has a tortuous path), and the soft tissue of the tube may be collapsible, thereby resulting in multiple constrictions when attempting to pass. As described above, this may be particularly true at the uterotubal junction (UTJ), which may be muscular and thus more prone to perforation by the insertion of medical devices. 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 1mm.

In at least one embodiment of the present disclosure, the elongate balloon that is initially everted into the 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 the advancement of a push wire, which may be consistent with pressurization. The balloon may be substantially inelastic for a substantial portion of its length so that the balloon does not substantially expand and dilate the fallopian tube when everted. Inflation of the balloon may rupture or otherwise damage or damage the fallopian tube. However, exemplary embodiments may also incorporate a resilient distal balloon end that is expandable to seal the distal neck as the distal balloon is retracted. In some embodiments, the device may have a balloon that is sufficiently rigid to cannulate the fallopian tube and flexible enough to navigate through the tortuous path of the fallopian tube to minimize 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.

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 surprisingly been found that the action of extending a portion of the catheter can remove sufficient cell and/or tissue samples from the wall of the fallopian tube for histological and/or cytological evaluation. For example, at least a portion of the balloon length 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 does not substantially expand and dilate a body lumen (e.g., fallopian tube) when everted. In some embodiments, the balloon may be sized such that the body lumen does not expand or distend as the balloon everts. As described above, inflation of the balloon may rupture or damage the body lumen of the subject. According to some embodiments, and as discussed above with respect to the exemplary balloon catheter, the balloon may extend longitudinally only into the body lumen by everting from the catheter such that the balloon does not substantially expand and dilate the lumen when the balloon is everted or extended into the body lumen (e.g., 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% greater than the diameter of the fallopian tube. Radial expansion of the balloon may be limited or controlled by the substantial inelasticity of the balloon's majority of its length. It should be appreciated that the portion of the balloon that is not intended for insertion into the luminal structure may be elastic and thus may be diametrically expandable and compliant, rather than being substantially inelastic. Such hybrid capsules may be well suited in some embodiments when sealing with UTJ is required. Exemplary conditions requiring sealing may include flushing the lumen, filling the lumen with imaging contrast agent, diagnosing an occlusion, and/or localized contact with a therapeutic agent (such as a chemotherapeutic agent or antibiotic).

It has also surprisingly been found that retraction of the extended portion of the capsule allows more cells to be removed. In some embodiments, the extension portion may be retracted prior to catheter removal to prevent the retrieved oviduct cells from spreading to surrounding tissue. In some embodiments, the 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., cancer cells). In some embodiments, a staining agent may be released in the fallopian tube for identifying abnormal and potential cancer cells.

Referring now to fig. 2A-2D, the everted inelastic sleeve 12 and attached distal elastic balloon 14 may be inserted through an introduction catheter 10, the introduction catheter 10 may be in the working channel 22 of a surgical hysteroscope 20 (fig. 3) and used to cannulate the proximal neck of the fallopian tube 1 as shown in fig. 2A. In fig. 2B, the balloon can be inflated to evert the sleeve 12 the length of the fallopian tube 1 and expand the distal elastic balloon 14. In fig. 2C, after the everting elastic sleeve 12 has been fully advanced and the elastic balloon 14 has been inflated, the balloon may be at least partially retracted proximally to seal the distal neck 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. Retraction of the inflated elastomeric bladder 14 seals the opening of the distal neck finish. The irrigation fluid is then collected to obtain a sample of cells from substantially the entire length of the fallopian tube 1 for cellular analysis in the detection of ovarian cancer or other health condition. 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 staining agents may include fluorescent imaging agents attached to a modified type of folic acid that can be used as homing devices for searching for ovarian cancer cells to attach thereto. In some embodiments, the multispectral fluorescence camera may illuminate the detected cells, visually identifying their location, such as through a monitor. For the growth and division of ovarian cancer cells, the cells require a large amount of vitamins (folic acid). The specific receptor on the surface of the cancer cell grabs the vitamin and anything it attaches to and pulls it into the interior.

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

In embodiments of catheter 10, 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 inelastic 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 ridge may extend inwardly when the tube is everted prior to deployment. As the ridge extends outward, as shown in fig. 5B, the ridge 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 upon retraction of the balloon, for example, by additional surface area and/or frictional contact. In some embodiments, the outer surface of the everting inelastic balloon may be covered with a fabric or otherwise textured, which may increase cell removal and improve cell collection during balloon retraction, as described below.

Fig. 6A-6C illustrate an exemplary embodiment of an everting sleeve catheter 10A, the everting sleeve catheter 10A may protect the junction between the balloon 14A and the sleeve 17 of the everting sleeve catheter 10A during deployment. 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 having a length slightly shorter than the elastic balloon 14 may be attached to the elastic balloon 14 at the distal end of the catheter and may be invertible such that in the 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 located inside the inelastic sleeve 17, e.g., the inelastic sleeve 17 is disposed outside of the elastic balloon 14A and may constrain the elastic balloon 14A along its length, e.g., most of its length, to prevent the elastic balloon 14 from expanding and potentially rupturing the fallopian tube during its travel through the fallopian tube. When the balloon/sleeve is fully everted, the distal elastic balloon may be inflated to about 3 to 5 times the sleeve diameter for occluding the distal neck with concomitant pull back of the inflated balloon as the catheter is retracted. In some embodiments, the catheter may contain a port 11 to allow flushing to occur between the balloon and the inelastic sleeve 17.

Fig. 7A-7C illustrate an exemplary embodiment of an everting sleeve catheter 10b comprising a concentric double-walled catheter with three layers of everts attached to the distal catheter tip. An elongate inelastic balloon 21 may be attached to the distal end 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 elongate elastic balloon 14B may be equal to the length of the inelastic balloon 21, and the elongate elastic balloon 14B may be attached to the distal end of the outer wall 27 of the catheter 10B. Bladder 14B may be disposed within inelastic bladder 21. Inelastic sleeve 29 may be attached to the distal tip of outer catheter wall 27, and in some embodiments inelastic sleeve 29 may be shorter in length than elastic balloon 14B. Sleeve 29 may be disposed inside elastomeric bladder 14B in an undeployed state. Pressurization of the inner catheter 23 may evert the inelastic balloon 21, and the inelastic balloon 21 may deliver the elastic balloon 14B and the outer inelastic sleeve 29. After all three layers are fully everted, pressurization between the walls of the inner and outer conduits may inflate the elastic balloon 14B. Inelastic sleeve 29 may constrain elastic balloon 14B along most of its length. The distal unconstrained tip 14T of the balloon may be inflated to form the occlusion element. This may be advantageous to reduce friction in the system during eversion. For example, inelastic balloon 21 may deliver elastic balloon 14B and inelastic sleeve 29. The elastic balloon 14B does not undergo inflation until fully everted. In this way, the elastic balloon 14B may avoid frictional contact with the wall of the inelastic sleeve 29 during eversion, which may be advantageous to facilitate deployment, for example, when working with small diameter catheters for traversing the fallopian tubes.

Fig. 8A-8B illustrate an exemplary embodiment of an everting sleeve catheter 10C including a non-elastic sheath 29A having a small lumen 31 for irrigation, wherein the sheath 29A may be connected to a third port 11A for fluid irrigation and aspiration to obtain a cytological specimen. As noted above, in some embodiments, the rinse fluid may contain a stain for identifying abnormal and potential cancer cells.

Another exemplary embodiment according to the present disclosure is shown in fig. 9A-9C and fig. 10A-10B. An elongate balloon 32 including an extension 34 (e.g., an inflatable member) may be everted into a lumen 36 of catheter 30, and extension 34 may be attached to a distal end of balloon 32. In an inverted, e.g., undeployed, state, the extension 34 may be positioned within the elongate balloon 32. In some embodiments, the extension 34 may be a spiral of one or more turns of filaments 38. The filaments forming the extensions 34 may be formed from a variety of materials, including, for example: monofilament polymeric 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 a fallopian tube (not shown) for subsequent return to the location of the cell sample. It will be appreciated that the extension may also have alternative configurations, such as an inflatable member. The extension 34, e.g., 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 34 may be included as an elongated strand of material 38 that, when released from being constrained within the catheter, the strand of material 38 curls, disperses or fans out 42, curls 44 to a predetermined shape (fig. 11A-11F or fig. 14A-14B), or a combination thereof. In some embodiments, the extension 34, e.g., an expandable member, may be formed from compressed polymer foam (which self-expands when released into a wet environment) (fig. 12A-12B). Upon pressurizing the catheter adjacent the proximal neck, the balloon 32 may evert, pushing the everted portion outward to an extended position and into contact with the cells of the inner wall of the fallopian tube. In some embodiments, extension 34 may extend out of the distal neck of the fallopian tube and into the abdominal cavity when the balloon is fully everted. In some embodiments, the extension 34 may have an expanded outer diameter of about 5-15 mm.

An advantage of having an extension 34 of multiple bristles is that the surface area over which a 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 as 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, the cell collection per linear unit of the fallopian tube so engaged under similar pressurization conditions can be increased as compared to an unconfined extension.

In still other embodiments of catheters according to the present disclosure, the extension, e.g., expandable member, may be formed in any number of shapes and contours. For example, a plurality of filaments 42 may be attached to the distal end of the balloon 32 that expand to form the brush 42 when the balloon is everted (fig. 11A-11B). In some embodiments, the braided string or suture 43 may extend distally of the 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 the suture 43 (see fig. 11E-11F). The polymer foam structure 46 may be compressed within the balloon 32 and may self-expand in response to eversion of the balloon 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 a superelastic coil (fig. 14A-14B), a spiral 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 gather into a three-dimensional structure (such as an inner lumen 54) when the balloon is everted, and an inflatable member 34 with a plurality of outwardly oriented bristles 40 (fig. 18), or a combination thereof. It will be appreciated that the catheter extension as an expandable member or any of the other of these 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, such as through the inner lumen 54 or through the balloon 32. Such markers are well known in the art and illustratively include radio-opaque markers, isotopic markers, and radio-frequency markers. In still other embodiments, the biodegradable extension or 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 agent, or a combination thereof, to fallopian tube 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 interior surface of the fallopian tube. In some embodiments, the extension may be everted back into the interior of the balloon by reducing the gas pressure within the balloon, and the balloon again everted into the catheter tip region to shield the collected cells with the catheter tip region interior openings. In other embodiments, the extension and balloon (in a contracted state or remain inflated) may be retracted into the sheath without the need to re-evert 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 the inflatable filament 38 shown in fig. 18-20, may be attached to one end of the varus balloon. In some embodiments, an extension 34, such as an inflatable coil, may be connected to the push wire (see fig. 23A). In some embodiments, the extension may be connected to the distal end of the push wire 134. In some embodiments, the extension portion 34 (e.g., a spiral) may be a collection device that passes through the lumen of the inner tube, which may be inflated upon 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 portion) and then protected by the sheath 162 in order to minimize the likelihood of the distal cells being scraped off the inner surface of the proximal fallopian tube when the device is removed.

In some embodiments, friction between the outer surface of the extension portion 34 (e.g., the expandable filaments 38) and the inner layer of the fallopian tube is sufficient to unseat the cells and adhere them to the expandable member, even in embodiments having an unsightly extension portion. For example, the inflation spiral at the distal end of the balloon may contact the umbrella at the distal end of the fallopian tube to collect the cell sample. Since the inner diameter of the fallopian tube increases as it extends from its proximal to its distal end, inflation of the extension portion 34 (e.g., by the inflatable filaments 38) can 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 cell sample when the hysteroscope is removed from the patient. An elastomeric seal at the proximal end of the working channel of the hysteroscope can seal against 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 retraction length required to ensure that the elongate balloon and distal spiral are fully within the hysteroscope working channel. Upon removal of the hysteroscope from the patient, a syringe containing saline solution may be attached to the luer fitting at the proximal end of the working channel in some embodiments. Saline may be used to flush cells harvested from the elongate balloon and the inflation spiral into the tube. It will be appreciated that the cells collected by the expandable member may be collected for detection by conventional techniques and may be ready 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, the inner lumen 54 may be sufficiently rigid to withstand the pressure of the balloon as it inflates and everts. In some embodiments, the inner lumen 54 may be formed of metal, composite material, or polymer, or a combination thereof, including polyethylene terephthalate (PET) material, and may be attached to a catheter, as shown in fig. 17A-17B. The eversion procedure follows that of the above-described embodiment with push wires that do not include a lumen. This embodiment may also include an inflation side port and proximal seal 33 that may allow the balloon 32 to be everted while maintaining fluid communication between the hysteroscope and the patient's body tissue through the orifice of the 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 pathway. Thus, these agents and rationales may illustratively include microbubbles for use as acoustic contrast agents, imaging agents for various forms of spectral imaging, or therapeutic agents for treating cells or killing cancer cells, or combinations thereof. The therapeutic agent may illustratively include an antibody specific for a cancer cell and carrying a chemotherapeutic agent or radioisotope, a chemotherapeutic agent, a radioisotope seed, an antibiotic, an antifungal agent, or a combination thereof.

Fig. 21A-21B illustrate cross-sectional views of exemplary embodiments of a balloon-tipped everting balloon catheter 120 according to the present disclosure. Ball 122 may be attached to a distal end of a spring tip 124 that is secured to a tube or catheter 126. It should be understood that "tube" and "catheter" 126 may be used interchangeably. Ball 122 may be provided to travel through the UTJ of the patient to minimize and/or avoid accidental penetration of the sidewall of the UTJ. Spring tip 124 may allow the distal end with ball 122 to bend around the corner and travel through UTJ. Spring end 124 and ball 122 may have an open lumen 128 that may extend through spring end 124 and ball 122. The diameter of ball 122 on spring end 124 may be about 0.8-1.0mm and the length of hollow spring end 124 may be about 1.5cm with an outer diameter of about 0.6mm. The hollow spring tip 124 may be formed of a metallic (stainless steel or superelastic metal such as nitinol) coil spring and is sleeved on the outside with a thin-walled polymeric heat shrink tube made of nylon, PET (polyethylene terephthalate) or similar material. In some embodiments, the spring tip 124 may be a metal coil spring co-extruded into a tubular polymer body. Hollow spring end 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. The everting bladder 130 may be located within the hollow spring end 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 introduction catheter 126 (e.g., a generally flexible tubular structure).

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

According to some embodiments, a seal 137 may be provided within the tube/catheter shaft 126, with 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 catheter 126 to actuate the balloon 130 between the everted and everted positions while maintaining pressure in the catheter 126. Various embodiments of the present disclosure may provide an adjustable seal 135 disposed adjacent to the conical seal 137. In response to leakage developing between push wire 134 and conical seal 137, 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 is adjustable 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.

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

In some embodiments, the elongate balloon may be initially turned inside out into the catheter lumen during assembly, e.g., the balloon may be turned inside out during assembly. The balloon may be pressurized for deployment such that the balloon everts and "deploys" into the fallopian tube. The everting deployment mechanism may 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 expand and distend when everted, e.g., so that the fallopian tube does not expand or distend 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 the 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 by a conventional hysteroscope. Regardless of the mode of deployment, the retracted portion of the balloon within the catheter shaft 126 may be extendable from within the catheter shaft 126 into contact with the inner wall of the fallopian tube. It has surprisingly been found that the act of extending the portion may abrade a sufficient amount of cells and/or tissue from the wall of the fallopian tube for histological evaluation. This was observed for a flat surface with a balloon that appeared to be free of wear features. 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 significant histological evaluation, whether the balloon is fully inflated or partially contracted and collapsed. It has also surprisingly been found that retraction of the extension portion can remove more cells. In other embodiments, the extension portion may be retracted prior to catheter removal to prevent the dislodged oviduct cells from spreading to surrounding tissue. With the catheter removed, the exposed portion of the extension (now covered by cells) contacted with a microscope slide or other diagnostic substrate may be sufficient for detection of abnormal cells and especially cancer cells.

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

Fig. 22A-22C illustrate an exemplary embodiment of an everting capsule 130 according to an embodiment of the present disclosure, the everting capsule 130 exiting from a flexible tip 152 with a spherical ball 122. The nylon flexible tip 152 and ball 122 may be configured to travel through the patient's UTJ for deployment of the everting balloon 130 in the fallopian tube. In one embodiment, the balloon-tipped everting balloon catheter 150 may be configured with a spherical tip of about 0.9mm on a tip of about 0.66mm diameter X18 mm in length. In some embodiments, the tip may be formed of nylon. In some embodiments, the 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 tip catheter or device 160 according to the present disclosure. In some embodiments, the balloon 130 may have an outer diameter of about 0.8-1.0mm, and may have an initial everting length of about 1-3cm (e.g., about 1.2-1.5cm extending from the distal end of the cannula or catheter 126). The balloon 130 may be fully evertable into the fallopian tube, for example extending approximately 7-12cm. Balloon 130 may be secured to the distal end of catheter shaft or tube 126 (as shown at 117) and push wire 134 (as shown at 118). For example, the distal end 118 of the push wire 134 may form one end of the balloon 130. In some embodiments, the balloon 130 may be coupled to the distal end 118 of the 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, the push rod or wire 134 may actuate the balloon 130 from the everted position in the catheter 126 to the everted position. In some embodiments, the everting position may include a portion of the balloon 130 extending at least beyond the distal end of the tube 126. In some embodiments, balloon 130 may be initially partially everted and secured to catheter 126, forming rounded end 130a. In some embodiments, balloon 130 may be inflated with a fluid to a pressure of about 14-24atm (206-353 psi).

In some embodiments, as described above, device 160 may include sheath 162. Sheath 162 may be coaxial with catheter 126. The sheath 162 may be slidably adjustable relative to the catheter 126 to cover at least a first length of the balloon 130 extending outwardly from the distal end of the 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, the balloon 130 may extend an initial length (e.g., about 1.5 cm) from the catheter 126 during insertion through an endoscope. When the balloon is actuated (e.g., via push wire 134 and/or balloon pressurization), sheath 162 may protect the balloon 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 the balloon is everted. In some embodiments, a portion of sheath 162 may be at least partially translucent, optically transparent, or a combination thereof, as shown at 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 balloon 130 (e.g., to confirm positioning and/or complete balloon extension) using hysteroscope 20 through at least a portion of sheath 162 and/or catheter 126. 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 pressurized balloon 130 may have a rounded end 130a for atraumatic cannulation of the proximal neck and advancement within the fallopian tube, as well as a degree of flexibility along the length of the balloon 130. The balloon 130 may have sufficient column strength to allow the balloon 130 to be manually advanced through the UTJ under at least partial or no pressure, for example, using push wire 134. In some embodiments, balloon 130 may be constructed of a thin-walled polymeric material, such as polyethylene terephthalate (PET), polyethylene, nylon, polymer, or the like. The wall thickness of balloon 130 may be from about 0.0001 inches to about 0.001 inches, and in some embodiments, between about 0.00019 inches to about 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 upon deployment and in terms of cell collection. For example, a balloon wall that is too thin may result in the balloon lacking sufficient column strength (more compliant or elastic as desired), or a balloon wall that is too thick may result in the balloon 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 the 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 adhere or tend to stick to itself during eversion or after retraction and retrieval with the catheter.

In some embodiments, the first marker 171 may be disposed on at least a portion of the catheter 126. The first indicia 171 may be a readiness 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 the balloon 130 during preparation and initial insertion into the fallopian tube. In some embodiments, at least a portion of the catheter 126, such as a proximal portion connected to the transparent portion 167, may 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 extend distally an initial length as a preparatory step to cover an everted balloon 130, for example, about 10 to 20mm in length, for accessing the proximal neck finish before the balloon is fully everted.

When in place at the proximal neck, the sheath may be pulled back from the first marker 171 to the initial position, exposing a 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. As sheath 162 extends distally of catheter 126, the distal tip of sheath 162 may be an indicator of balloon travel. The first indicia 171 may include score lines, coating material, or selectively oxidized regions. In some embodiments, the first indicia 171 may be a strip 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 catheter 126 (e.g., the metal portion or hypotube 138) using, for example, an adhesive, bonding, or welding process. Such a readiness marker may allow a medical professional to know how far to deploy balloon 130 in the initial preparation 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 guess 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 medical professional may use the markers as visual counters or measuring devices to determine the approximate length of the balloon that has been everted. It should be appreciated that any of the inner cannulas or catheters described herein may include a marker as described for assisting navigation through the anatomy of the patient.

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

In some embodiments, under conditions of use, portion 167 of catheter 126 and/or the distal portion of sheath 162 may have a transparent portion along its length, or a portion that is translucent, optically transparent, or a combination thereof. According to embodiments of the present disclosure, the tube or catheter 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 indicia 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 may be radiopaque. The third indicia 179 may 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 visualized as the balloon 130 is advanced beyond the sheath 162 into the fallopian tube. As the catheterization step proceeds, the third indicia 179 may allow the user to visualize the distal end of the catheter 126. The user may be able to see when the intubation step is complete, e.g., when the third indicia 179 is aligned with the end of the sheath 162 at the neck finish, thereby improving ease of use. The third mark 179 may be formed by the same technique used to form the first mark 171 and/or the second mark 173. The third indicia 179 may be provided in a readily visible color (e.g., black or blue).

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

In some embodiments, at least a portion of the string, braid, and/or suture 121 (e.g., as shown by 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 balloon 32, 130 is everted. In some embodiments, the string or suture 43, 121 may be a plurality of braids. In some embodiments, the string or suture 43, 121 may be formed of one or more colors, for example, to enhance visualization by a medical professional to confirm that the balloon is properly everting (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 may be visualized through the endoscope. As the balloon 32, 130 is everted, the string or suture 43, 121 inside the balloon 32, 130 may extend out of the balloon at a distance approximately twice as great as when the balloon is everted (e.g., about 2mm of the string or suture is exposed outside the distal end of the inner cannula/tube when the balloon is everted 1 mm). The color may determine the positioning of the suture or string 43, 121 in the fallopian tube for sample collection. In some embodiments, the string or stitch 43, 121 may include one or more areas with 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 apart along its length in predetermined known increments 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 approximation of the 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, for example, test cells, inks, coatings, adhesives, laminates, and paints, or combinations thereof. The surface treatment may enhance wettability to produce a surface having hydrophilic properties, or hinder wettability to produce a surface having hydrophobic properties. Surface treatments may be used to improve the adhesive properties of the surface of the capsule to create a surface to which cells adhere more readily than untreated surfaces.

Surface treatments may also be used to prepare the surface of the capsule to print indicia on the surface, including PAD printing, for example. PAD printing (also known as over-imprinting) is a printing process that can transfer a two-dimensional image onto a three-dimensional object. The logo printed on the surface of the balloon may serve as a ready indicium for the user. These readiness marks may allow the user to know the length of the balloon 130 prior to deployment of the 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 guess or visual observation on the part of the user.

in addition to markers for visualization purposes, the balloon 130 may also be treated with a process that increases surface area, such as the application of nanofiber or micropillar surfaces (e.g., including but not limited to Corning (Corning) corporation)) This may increase the cell collection yield and/or retention rate compared to vesicles with little or no surface treatment. Suture or string 121 may include similar surface treatment features as a means of enhancing cell collection and retention.

In various embodiments, the balloon 130 may be formed of the following materials: this material enables the balloon 130 to move between the everted and everted positions without excessive deployment pressure, yet is sufficiently rigid that the balloon does not excessively radially expand during eversion. The material may also allow for formation of wrinkles, overlapping material or micro-ridges or combinations thereof on the balloon surface during manufacture and/or assembly, for example by polymer deformation. Such folds, overlapping materials, or micro-ridges may be created on the generally smooth (non-contoured) balloon surface material, or may enhance the balloon surface material already including one or more surface features. Folds, overlapping materials 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. Folds, overlapping materials, and/or micro-ridges may improve cell collection of the balloon 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), such that cells may remain within the folds of balloon 130 when balloon 130 is retracted into sheath 162 and catheter 126 is removed with the endoscope. Relieving the pressure in the balloon prior to deflation, allowing the balloon to collapse or partially collapse, may increase or reform wrinkles on the balloon surface, and further improve cell collection and/or retention. In some embodiments, the surface of the balloon 130 may be roughened or otherwise conditioned to increase the surface area. According to various embodiments, the bladder may be made of polyethylene terephthalate (PET), polyethylene, nylon, fluoropolymer or perfluoropolymer, or other similar suitable material.

In some embodiments, a surface area of the 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 relatively smooth balloon surface due to material properties may be altered to include wrinkling and increased surface area, such as by a process employed during manufacture or packaging that applies surface features to the balloon surface and remains during use of the device. In other embodiments, the surface of the balloon material that is maintained relatively free of any topography may still be able to collect and retain cells simply by the mechanism of everting the tissue lumen and engaging it with the balloon as described above, and then (optionally contracting the balloon and) retracting the balloon along the tissue wall. In some embodiments, the surface of the balloon 130 may be embossed to impart micro-ridges having peak-to-valley heights of about 0.1 to 500 microns by a variety of 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 varus/valgus, 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 contours that minimize potential interlocking.

In some embodiments, the polymer surface of the balloon 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 advantageous to increase the surface area without creating stress on the bladder with the embossing tool contact. This feature may improve cell collection of the capsule by increasing the surface area and creating a micro-edge that is orthogonal to the axis of the capsule when the capsule is removed. In some embodiments, as described above, polymers with low surface energy and/or limited ability to curl/pucker at any balloon thickness during stamping and/or etching are still useful herein for cell biopsies, as the opposing contact surfaces have sufficient slip to allow the balloons to evert smoothly, while having sufficient surface area to remove and retain cells. The low surface energy polymer in embossed or etched form may comprise a fluoropolymer, a perfluoropolymer, a polyalkylene, a polypyrrole amide (Kapton H) or polystyrene, or a combination thereof.

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

The balloon 130 may be translucent, optically transparent, or a combination thereof. In some embodiments, the 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 the visibility 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 that are released within the fluid. Colloid or suspended particles useful herein include, but are not limited to, polymethyl methacrylate, mica, barium sulfate, starch, and combinations thereof.

The length of the fully everted balloon 130 may extend to about 7-12cm within a lumen (e.g., fallopian tube) such that when fully everted, the balloon 130 may extend within the fallopian tube of the patient as at least a portion of the length of the everted balloon successfully progresses through the UTJ. Eversion of balloon 130 may be performed in a controlled manner, for example, by advancing pushrod 134 through fluid-tight seal 135 at the proximal end of catheter 126. As described above, at least a portion 167 of the catheter 126 may be transparent or translucent such that movement of the balloon 130 may be observed through a hysteroscope in which the catheter 126 is inserted, thereby providing a direct view of the insertion process to 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 a polymer or metallic coil or woven reinforcement, or a combination thereof.

In some embodiments, the transparent or translucent portion 167 of the catheter 126 can be at least about 1cm in length for visualization of balloon deployment through hysteroscopic viewing. Providing a transparent or translucent portion 167 of sufficient length can ensure visualization of balloon deployment while providing sufficient catheter column strength for tubal cannulation. In some embodiments, the transparent portion 167 of the catheter 126 may have a length relative to the opaque portion (e.g., the metallic hypotube portion 138) to balance the desired column strength and support for the catheter 126 if visualized at the distal end. In some embodiments, the transparent portion 167 can extend within the metal portion 138 to the proximal end of the device. It should be appreciated that the material used to form the transparent portion 167 of the conduit 126 may have a lower column strength than the metallic hypotube portion 138. This balance may improve ease of use (e.g., by visualizing 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, the balloon 130 may not remain straight when the balloon 130 is at least partially turned out of the catheter 126 or cannula. Conversely, balloon 130 may exhibit an undesirable 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, as well as advancing the balloon through the UTJ. The extended length of the everting balloon 130 may be straightened or held straight by the use of an outer sheath 162, the outer sheath 162 being coaxial around the exterior of the catheter 126 or cannula, and may assist in providing column strength and coverage of the partially everting balloon tip. 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 a catheter is inserted, thereby providing a direct view of the insertion process to the user. Similar to catheter 126, 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 a polymer or metallic coil or braided reinforcement, or a combination thereof. The sheath may be aligned with respect to the catheter and/or balloon to provide column strength to the balloon. In response to the balloon passing through the UTJ cannula into the fallopian tube, 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. Sheath 162 may also protect samples (e.g., cells) collected on the balloon and/or extension. For example, the sheath 162 may protect the balloon in the 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, sheath 162 may remain stationary relative to balloon 130 and/or catheter 126 such that balloon 130 is received in sheath 162 after cell collection. When the balloon 130 is retracted 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 distending fluid in the uterus or irrigating fluid in the fallopian tube or uterus. For example, the cell-collected vesicles may be exposed to environmental conditions, which may render the sample collection unusable, and/or otherwise wash the cells from the vesicles and the extension portion.

Fig. 35 illustrates an exemplary embodiment of linear eversion of a balloon 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 moved at point Y (e.g., reference numeral 118 shown in fig. 23A). The balloon 130 may be everted from the position shown in step 1 to the position shown in step 2 and then to the position shown in step 3. During eversion, points a, B and C move to the left of the figure, e.g., extend distally of the distal end of device 160. Point a may move from the inner surface to the outer surface of the balloon 130 when the balloon is deployed/everted at/towards the left of the figure. In practice, the 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 (up to about 7-12cm total oviduct length) can be achieved by further rotation of the drive wheel 204 (see fig. 25). The balloon 130 may then be contracted by relieving the pressure in the inflation device. The 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 can optimize tissue collection inside the fallopian tube. While retraction 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 an 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 contracted to create multiple edges and/or overlapping materials to facilitate cell collection. The edges may function in a manner similar to the edges of a curet or the edges of a jaw in a biopsy forceps. Similar to these features on other collection devices, the edges formed by the pleated capsule can focus the contact force on the anatomical wall to collect cells.

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 balloon by immersing the balloon and/or extension (if used) in a cytological preservative and shaking to agitate the cells. Alternatively, the balloon, extension and/or sheath may be cut and placed into a cytological preservative. In some embodiments, the sheath may be extended and deployed over the balloon as the balloon is contracted and removed to protect the tissue sample collected on the balloon surface.

Fig. 24 shows a side cross-sectional view of a balloon tip catheter 160' including a superelastic pushrod 175 and a spiral carrier 176. In accordance with embodiments of the present disclosure, the screw 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. The pushrod 175 may be constructed from a superelastic material such as nitinol (nickel titanium compound) wire. At least a portion of the length of pushrod 175 may be wrapped into a coiled carrier 176, which may be made of polyethylene or polytetrafluoroethylene (teflon). The outer spiral diameter of the carrier is about 8cm, making the proximal operating length of the catheter handle more compact. The screw carrier 176 may be attached to the proximal seal 135 on the catheter by a flexible band 177. In some embodiments, the flexible strap 177 may be constructed of a polymer or silicone rubber material. In some embodiments, the ram 175 may have a diameter of about 0.025 "or some other thin diameter, which may be detrimental 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 over the pushrod 175, but may provide a grip for travel of the pushrod 175 when compressed between the thumb and index finger. 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 compound. In some embodiments, the flexible grip may have an internal dimension 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 may be a sliding fit with the pushrod 175.

Fig. 25 shows an exemplary embodiment of a balloon end catheter 200 configured with a handle 202. In some embodiments, handle 202 may be included in 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 wire 134, 206 and may control actuation of the push wire 134, 206, which in turn may control actuation of the balloon 130 between the everted and everted positions. The handle 202 may include a drive wheel 204 for advancing and retracting the push wires 134, 206, wherein the balloon 130 may be linearly everted (e.g., gradually opened or deployed from 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 notches or knurling patterns to facilitate gripping of the wheel during operation of the catheter 200. The outer edge of the drive wheel 204 may include a plurality of arrow-like features that facilitate gripping and/or may indicate the correct direction of travel of the drive wheel. The top surface of the drive wheel 204 may have an arrow molded into it for indicating the correct direction in which to turn in order to evert the bladder. The opposite side of the drive wheel 204 may include square bosses 222 that may be inserted into a drive gear 224. In some embodiments, the gear mechanism 220 may include a reduction gear arrangement 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 be rotated a greater distance to achieve the same extended length of balloon eversion than if no reduction gear arrangement were included or a different reduction ratio were included). The net effect may be a finer control of the eversion of the balloon 130 as the 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 advancement, 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 extension tubes 168, 216 or luer fitting 218 of handle 202 (see fig. 26A-26B). Once catheter device 200 is pressurized, the user may rotate drive wheel 204, thereby causing pushwires 134, 206 to travel. Although in some embodiments the balloon 130 may be everted under pressure without the need for the drive wheel travel of the push wires 134, 206, it should be appreciated that the drive wheel 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 act as an introducer when the sheath 162, 212 is locked onto the body of the catheter 126, 210. The sheath knob 214 may be sufficiently compliant to allow the user to move the sheaths 162, 212, such as for a pre-extension portion of the balloon, and into the fallopian tube when desired. In some embodiments, the sheath knob 214 may be sufficiently tight so that unintended 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, with the extension tubes 168, 216 attached to a luer fitting 218 in the handle body, for example, 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 everted 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 of the gear mechanism 220 and single user operation. A ring "a" as shown in fig. 26A may be included in the handle 202 and features 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 inside the ring "D" for a small hand or outside the ring "E" for a large hand.

In some embodiments, the drive wheel 204 may have a square boss that may be inserted into a square hole 222 of a drive gear 224. The healthcare professional operable drive wheel 204 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 a direction indicated by arrow 228A, which may be the opposite direction to arrow 224A. Also, the idler gear 226 may 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 may extend between surfaces on and between each of four gears (224, 228, 230, 232) that may each rotate as indicated by arrows 224A, 228A, 230A, 232A in fig. 26B during advancement of the balloon 130 via 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 rubber or silicone rubber or polyurethane).

The balloon 130 may be advanced until the proximal end of the push wires 134, 206 is between the drive gear 224 and a first gear 228, which may be mechanically coupled to the first gear 228. Once the push wires 134, 206 have passed over the gear mechanism 220, further rotation of the drive wheel 204 does not cause further travel of the balloon 130. Since the user may feel that there is no push wire 134, 206 in gears 224, 228, 230, 232 when the tactile indicator of balloon 130 is fully everted. By mechanically coupling with push wire 206, gear mechanism 220 may allow for fine, precise, and controlled movement of deployment and/or retraction of balloon 130 by eversion and inversion, respectively. As already mentioned, the drive wheel may provide a slow and even 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 gear ratio of 4 to 1, or a gear ratio of 2 to 1, and it should be appreciated that any other gear ratio may be used to provide control of capsule travel. The gear ratio may be configured to provide slow gear rotation. This may ensure that the deployment speed of the balloon is controlled (e.g., slow and uniform) between users, thereby increasing safety by reducing the risk of adverse events such as perforation.

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 advancement of the push wire and/or unidirectional balloon movement. In some embodiments, the limiting 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 (drop key-click in mechanism). At a predetermined maximum extension, as shown in fig. 26E, the pawl 242 may engage with one or more gears (e.g., gears 224, 228, 230, 232) to form a gear jam. The pawl 242 may be activated to stop further travel of the balloon 130. In some embodiments, the pawl 242 may be any mechanism configured to engage with 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, thereby causing jamming and preventing further rotation. Alternatively, a rack and pawl gear, linear gear, or 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 movement is shown. Ratchet is a mechanism used to limit movement in one direction. The ratchet can have three main parts: a linear gear rack 233, a pawl 235 (e.g., a "catch") and a base or mount 237. The edges on one side of the teeth 239, 239' on the linear rack may have a steep slope, while the other edges of the rack teeth may have a moderate or gradual slope. For example, the edges of one side of the teeth 239, 239 'may be steeper than the edges of the other side of the teeth 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 rack and pinion 233. When the linear rack is moved linearly in the first direction, the pawl 235 can slide over the teeth 239 without limiting the natural movement of the device. When the direction of movement is reversed to the second direction, the pawl 235 may contact a steep slope on the gear teeth 239 to resist movement. The pawl 235 may be spring biased downwardly into the linear rack and pinion 233. In some embodiments, a spring, such as a torsion spring, may be provided at the pivot point 236, such as at a first end of the pawl 235, for pivotable rotation of a second end of the pawl 235. In some embodiments, a spring, such as a linear spring, may be provided at the 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 pawl 235 can be mounted to the mount 237 in generally fixed relation to one another, with the rack sliding relative to the mount and the pawl 235 being pivotally connected to the mount. 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.

Restrictions 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 restrictions on the travel of the push wire 206, for example, as shown at "F". During advancement of the push wire 206, the pawl 238 may be biased from the linear gear rack 233, as shown in detail "F" of fig. 26A. In some embodiments, the pawl 238 may pivot about a point, as indicated by reference numeral 221. The linear gear rack 233 may be directly attached to an end of the push wire 206 remote from the balloon 130 in the handle 202. When the pawl 238 hits the stop 243, the travel of the push wire 206 may automatically stop 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 a user to overcome the spring bias on the pawl 238, thereby allowing the pawl 238 to lift from the linear gear rack 233 and allow the push wire 206 and attached balloon 130 to retract. In another embodiment of the ratcheting action other than linear rack and pinion 233 in fig. 26D, push wire 206 may continuously and smoothly travel and wrap around deployment wheel 245 until pawl 235 reaches stop 247 and engages stop 247 to stop further travel of balloon 130. In fig. 26E, the pawl 235 may act as a gear jam when the extension limit of the balloon 130 is reached.

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

In some embodiments, sheath 162 may be compatible with standard hysteroscopes 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 sheath inner diameter large enough to accommodate balloon 130. This balance may increase cell collection efficiency, for example, by having an inner diameter sufficient to retain the balloon 130 without inadvertently removing (scraping) cells from the balloon surface. It should be appreciated that the balloon 130 may remain within the sheath 162 in the inflated and/or deflated state.

As already mentioned, a sheath knob 164 or male luer lock fitting including a connector of Tuohy-Borst seal 136 may be included at the proximal end of sheath 162. A Tuohy-Borst adapter comprising a seal 136 is a medical device for forming a seal between devices and attaching a catheter to other devices. Tuohy-Borst seal 136 may be tightened to a snug fit with the catheter or cannula holding sheath 162 in place. Sheath knob 164 may mate with a female luer lock fitting (if any) at the instrument port on the working channel of hysteroscope 20. Referring again to fig. 3, a male luer lock or sheath knob 164 may be connected to instrument port 23 such that catheter 126 and/or sheath 162 may be moved with 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 connectors are connected, the tip of sheath 162 may protrude beyond the distal end of the hysteroscope, for example, approximately 2-3cm. The sheath 162 may also protect a portion (e.g., a length of about 1.5 cm) of the balloon 130 that is everted during device preparation from damage as the catheter 126 is advanced through the working channel of the hysteroscope. A stainless steel tube, such as hypotube 138, may be at least a portion of 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 obtain sufficient stiffness.

In some embodiments, hypotube 138 may ensure that handle 202 is not disturbed, or is not detached from the working channel of hysteroscope 20, when the device is released by a medical professional during a 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. Sheath 162 may form a physical barrier and may protect the balloon in at least one of the everted position, the partially everted position, and/or the fully everted position, and may serve to protect the collected cells from dislodging during transport out of the patient's body.

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

Fig. 23C illustrates the balloon end catheter 160 of fig. 23A (with a tube reservoir or extension tube 168) and inflation device 172 according to an exemplary embodiment of the present disclosure. It should be appreciated that in some embodiments, extension tube 168 may be similar to extension tube 216 as shown in FIG. 26A. The extension tubes 168, 216 may be configured to withstand increased pressure. Pressurization of the balloon 130 by fluid injection may be performed using a syringe device (such as the exemplary inflation device 172). The rotation of the threaded plunger shaft by the releasable lock may increase and maintain the pressure in the inflation device 172, while the pressure gauge 174 provided with the inflation device 172 may allow control of the input pressure. In some embodiments, balloon end 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. Extension tubes 168, 216 may be constructed of a polymer such as polyurethane or polyvinyl chloride (PVC), with or without a polymer or metallic coil or braided reinforcement. Extension tubes 168, 216 may contain some amount of inherent elasticity, while the everting bladder may be generally inelastic. Extension tubes 168, 216 may impart fluid capacity to the system when bladder 130 is fully pressurized. A small volume of fluid may be contained in the everting bladder, and this volume may be further reduced by the volume occupied by the pushrod 134 (e.g., when the bladder is everted, the pushrod 134 moves into the bladder 130). The resulting everted balloon volume may be smaller as compared to the larger volume in pressure tube 168, which may allow balloon 130 to evert over its entire length without significantly reducing pressure once balloon end catheter 160 is pressurized.

In response to positioning the stopcock valve 170 closer to or farther from the device and hysteroscope 20, a length of extension tubing 168, 216 may be added between the inflation port 166 and inflation device 172 on the device. For example, as shown in fig. 25, a luer fitting 218 may connect the pressure tubes 168, 216 for connection with the stopcock valve 170. In some embodiments, a stopcock 170 may be provided at the ends of extension tubes 168, 216 for connection with luer 219 and inflation device 172. In some embodiments, the stopcock 170 may be connected to the luer fitting 218. The stopcock valve 170 may be closed after pressurization and the inflation device 172 may be removed from the examination region prior to insertion and eversion of the balloon 130. During a medical procedure, such a single operator surgical procedure may be less cumbersome and more efficient. It should also be appreciated that in some embodiments, luer 219 may be connected to inflation device 172 without stopcock valve 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 so as to traverse the entire length of the fallopian tube. When the everting balloon 130 exits the catheter tip, the everting balloon 130 may form a curved shape at the end 130a, and the everting portion may comprise a double wall configuration. 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 advances a distance of approximately 14cm to produce an everted balloon length of 7 cm. This length of pushrod may initially extend rearward from the proximal end of catheter 126 directly into the face of the operator, making it cumbersome to use. The pushrod may also be susceptible to contamination by the sterile device due to its length, as it may extend into the physician's workspace during the surgical procedure. For example, the proximal end of the long pushrod 134 may contact the surgeon's face or surgical mask during use. Accordingly, it may be desirable to provide a pushrod system that does not have to extend the entire length of the pushrod 134 rearward. The superelastic pusher 175 and carrier design of fig. 24 and balloon end catheter 200 of fig. 25 configured with handle 202 may include a pusher bar and minimize and/or avoid the need to extend the pusher bar back toward the user.

Fig. 27 illustrates a side cross-sectional view of an exemplary everting balloon tip catheter 180 according to the present disclosure, including a tube 182 having a diameter less than the inflated diameter of the everting balloon 130 for insertion into a patient's UTJ. 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, the 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. The tube 182 may be of sufficient thickness and resiliency to support the balloon 130 to maintain the position of the balloon tip 163 (e.g., to maintain a straight position). In some embodiments, the diameter of the tube 182 may be smaller than the diameter of the balloon 130, such that the balloon 130 may remain flexible and compressible. Such flexibility may be advantageous to allow balloon 130 to travel through 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 of 0.033 "x 0.001" wall x1.5 cm long.

Fig. 28 shows a side cross-sectional view of an everting balloon tip catheter 190 that includes one or more flexible polymeric 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, strands 192 may extend into everting balloon tip 163, thereby supporting and holding the tip straight for insertion into the patient's UTJ. In some embodiments, the one or more flexible polymeric monofilament strings and/or sutures 192 may extend into the balloon tip 163 (e.g., approximately 1.5 cm). The monofilaments 192 may be formed of nylon, polypropylene, or other flexible polymeric materials or combinations 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 0.008" diameter monofilaments 192 in the everted balloon tip about 1.5cm long.

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

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

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

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

Fig. 32 illustrates a partial side perspective view of the band balloon 130S of fig. 32 prior to everting the band balloon 130S into a catheter or cannula, according to an embodiment of the present disclosure. The identifier 131 on the balloon provides a visual feedback indication of the progress of the balloon eversion. In particular embodiments, the indicia 131 may be about 1mm wide and spaced apart at about 1cm increments along the entire length of the balloon 130S. Alternate spacing of the bands on the balloon or other visual indicia may be spaced closer together for finer positional feedback, or farther apart for coarser feedback. Other visual indicia of the everting length may include sinusoidal markings having a known period length. It should also be appreciated that the length indicator may also comprise segments of different colors of known length.

Fig. 33 illustrates a side cross-sectional view of a balloon end catheter 280 configured with a ribbon balloon 130S, according to an exemplary embodiment of the present disclosure. As shown in fig. 33, the logo 131 of the out-of-band everting balloon 130S may be coupled with the transparent distal section 167 of the cannula or catheter 126 to provide visual feedback of the eversion of the balloon. In some embodiments, the indicia may be pad printed or scored with non-erasable indicia of highly visible color.

In some embodiments, the indicia 131 may be about 1mm wide, spaced apart in increments of about 0.5cm along the entire length of the balloon. Pad printing (also known as over-imprinting) is a printing process that transfers a two-dimensional image onto a three-dimensional object. Other patterns may be used in place of or in addition to the markings 131 on the surface of the balloon 130S. For example, the marks 131 on the balloon 130S may be spaced apart (e.g., about 0.5 cm), and dots may also be added in the remaining spaces between the marks 131. Each indicator 131 that enters the field of view in the transparent distal section 167 may indicate the length of successful eversion of the balloon 130S (e.g., 0.25cm, since the length of travel of the push rod is approximately twice the corresponding approximate length of eversion of the balloon (e.g., 0.5 cm)). Different thickness marks 131, as well as different color marks, or different numbers of marks, or combinations thereof, may be used in the same manner as described for the stripe and dot combinations. In some embodiments, color-coded segments may be added to the balloon 130S to indicate the extent of balloon eversion.

Additional embodiments of feedback markers (which may be externally visible to a physician external to the patient's body) are used to positive extent of capsular 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 apart in known increments to provide tactile feedback regarding the progress of the balloon eversion. The knotted string or braided suture may allow visualization of the advancing motion of the balloon as 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 the visibility of the knotted string or braided suture, the suture, logo or color-coded region may be provided in a color that is highly contrasted with the catheter and anatomy. In some embodiments, the braided surface of the suture may aid in 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 logo 131 in a manner similar to the balloon 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 maintained within the braid of suture 43, which may be superior to cells collected only on the suture surface. Cells trapped within the braid of suture 43 may be less likely to be inadvertently removed or scraped off during retraction of suture 43 and/or balloon 32, as cells may collect between the braids, thereby providing protection to 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, hues, or thicknesses relative to other strands. For example, as shown by the three strands of suture in fig. 11E, strands 47 and 49 of suture 46 may be a different color or darker shade than strands 51. Alternatively, as shown in fig. 11F, strands 47 'and 51' of suture 46 'may be a different color or lighter shade than strands 49'. The strands 47, 47', 49', 51' may be formed of a selected color along the entire length so that when in the weave pattern, a medical professional can visualize the color contrast or distinction along the weave length at a predetermined segment length. For example, each third portion, the first strands 47, 47' may extend a length L1, L1' over the outer portion of the suture 46, 46' (e.g., braided), each third portion, the second strands 49, 49' may extend a length L2, L2' over the outer portion of the suture 46, 46', and each third portion, the third strands 51, 51' may extend a length L3, L3' over the outer portion of the 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 chromatic aberration relative to the remainder of the strand.

An advantage of changing the appearance of the strands along the length of the sutures 46, 46' is that the appearance of the string or suture can be changed 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 movement of the suture through color contrast of the sutures 46, 46'. The string or suture may also be treated with surface modification (such as plasma, corona or nanofiber surface application) to alter its surface properties. In addition, the braided string, knotted string or suture may also provide additional tensile strength to the balloon, as the string or suture 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 bubbles with ultrasound, and sinusoidal patterns for the balloon, wherein the distance between maxima of the sine waves define the incremental distance of balloon eversion.

Navigation within the fallopian tube and indication of a clear path or obstruction may be provided by releasing microbubbles from the balloon tip or distal end of the balloon from its everted tube. The travel of the microbubbles can be tracked using imaging (such as ultrasound) to determine where a clear path exists. In the case of occlusion 251, such as an occlusion or constriction, the microbubbles may agglomerate or aggregate when blocked. In response to detecting a set of microbubbles, the medical professional can determine an occlusion. Fig. 36A shows a series of microbubbles 249 released from the end of the balloon 130 in the fallopian tube 1, wherein there is no constriction or obstruction, as indicated by the stable continuous line of microbubbles 249. In some embodiments, the 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 modulated on or off, wherein air is introduced into the fluid injected into the balloon 130. Fig. 36B shows a fallopian tube 1 having a tubular constriction or obstruction 251, wherein the tubular constriction or obstruction 251 would obstruct the flow of microbubbles 249, and the microbubbles 249 begin to agglomerate or clump at the point of the constriction or obstruction 251. The aggregation 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 blockage 251, the medical professional may perform additional imaging, such as ultrasound, to determine the location at which the balloon stopped.

The present disclosure further provides various methods of collecting cells from a lumen of a subject using embodiments of the catheter described above. These methods may include: using a catheter comprising at least a tube, a balloon (with or without an extension) secured to a distal end of the tube, a push wire actuating the balloon between an everted position within the tube and an everted position extending beyond the distal end, and a slidable sheath coaxial with the tube; a first portion of the balloon (according to some embodiments, about 1 to 2 cm) is everted 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 the 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 pushwire advances. The sheath knob may be advanced to a first marker on the hypotube and/or the catheter. The balloon may be everted to a point at the distal tip of the sheath. The distal tip of the sheath and the pre-extended balloon may be placed adjacent to 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 advanced further such that the initial portion of the everted balloon is inserted into the proximal neck.

The medical 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 length of the final eversion (e.g., about 7-12 cm) may be approximately equal to half of the push wire travel. When the balloon and/or suture are fully everted, the distal end of the push wire may remain in the catheter and may not contact the fallopian tube.

The fully everted balloon in the fallopian tube may fill the underlying space of the fallopian tube, thereby contacting the interior 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 collapse such that folds in the balloon surface may capture cells that collect on the balloon surface. In some embodiments, the balloon may cycle between inflation and deflation upon eversion for potentially increasing cell collection on the balloon surface and within the balloon surface features. In some embodiments, the suture may extend from the fully everted capsule, further collecting cells on the suture.

When cell collection on the balloon surface and/or suture is complete, the medical professional may retract the handle of the device while holding the sheath in place so that the everting balloon and/or suture may be retracted into the sheath. When aligned with the sheath knob, markings 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 the balloon surface and/or cells collected on the suture for removal of the device from the working channel of the hysteroscope.

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

any patent or publication mentioned in this specification is incorporated herein 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 specific embodiments of the present disclosure and is not meant to be a limitation on the practice thereof.

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 do not have to 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. An apparatus for fallopian tube diagnosis, comprising:

A tube having a distal end;

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

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; and

an actuator for controlling the travel of the push wire such that the balloon everts in a controlled manner upon pressurization;

Wherein the surface of the balloon includes a plurality of surface features for collection, retention, or both, of tissue samples of the interior surface of the fallopian tube, and

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

2. The device of claim 1, wherein the surface features comprise a plurality of pleats formed in the surface of the balloon, the pleats having at least one of a plurality of edges, micro-ridges, or overlapping materials, or a combination thereof.

3. The device of any of claims 1-2, wherein the actuator comprises a gear mechanism having a plurality of gears.

4. a device according to claim 3, wherein the gear mechanism has a reduction ratio for controlling movement of the capsule.

5. The device of claim 3, wherein the actuator includes a limiting mechanism on the plurality of gears for limiting travel of the push wire.

6. The device of claim 3, wherein the actuator comprises a pawl engageable with one or more of the plurality of gears.

7. the device of claim 6, wherein the pawl is spring biased toward the gear.

8. the device of any of claims 1-2, wherein the balloon is inflatable for moving the balloon from the first everted position to the second everted position.

9. The device of any of claims 1-2, 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.

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

a tube having a distal end, a push wire, an actuator, 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 the actuator is configured to control the advancement of the push wire such that the balloon everts in a controlled manner upon pressurization;

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; and is also provided with

wherein the surface of the balloon includes a plurality of surface features for collection, retention, or both of tissue samples,

11. The system of claim 10, wherein the actuator comprises a gear mechanism having a plurality of gears.

12. The system of claim 11, wherein the gear mechanism has a reduction ratio for controlling movement of the bladder.

13. the system of claim 11, wherein the actuator includes a limiting mechanism on the plurality of gears for limiting travel of the push wire.

14. The system of claim 11, wherein the actuator comprises a pawl engageable with one or more of the plurality of gears.

15. the system of claim 14, wherein the pawl is spring biased toward the gear.