SYSTEMS, METHODS, AND DEVICES FOR DELIVERING SUBSTANCES INTO A FALLOPIAN TUBE

A system for delivering one or more substances into a Fallopian tube of a patient may include a balloon catheter including a tube having a distal end, a balloon having a first end coupled to the distal end of the tube, and a push wire having a distal end coupled to a second end of the balloon, which may be hollow. The balloon may be movable between an inverted position and an everted position. The balloon catheter may be configured to receive the one or more substances such that the one or more substances may be retained by the balloon, or delivered through the push wire, or both. During eversion, or in the everted position, or both, the one or more substances may be delivered into the Fallopian tube.

FIELD

The present disclosure generally relates to Fallopian tube diagnostics and delivery devices that accommodate the anatomical difficulties associated with navigation in the Fallopian tube, and in particular to delivery devices, systems, and methods for delivering substances within the Fallopian tube.

BACKGROUND

The Fallopian tube is an extremely fragile anatomical lumen. Although medical procedures including research, preventative care, and treatment may require access into the Fallopian tube, the Fallopian tube may be prone to perforation during passage of most devices due to its fragile state. Access to the Fallopian tube may be necessary in medical procedures such as diagnostic procedures related to cancer diagnosis and treatment, in vitro fertilization (IVF), and/or artificial insemination (AI), or other therapeutic delivery devices. Some types of AI may include intrauterine tuboperitoneal insemination (IUTPI), which is an AI technique that involves injection of washed sperm into both the uterus and Fallopian tubes. Intratubal insemination (ITI) is an AI technique that involves injection of washed sperm into the fallopian tube. Gamete intrafallopian transfer is an AI technique where both eggs and sperm are mixed outside the woman's body and then immediately inserted into the Fallopian tube where fertilization takes place.

The introduction of diagnostic, treatment, and fertility devices to introduce substances into the Fallopian tube during medical procedures may be challenging due to the fragile structure of the Fallopian tube described above. Thus, there is a need for devices and processes to allow introduction of substances into the Fallopian tube during medical procedures in a less invasive and controlled fashion, and without the need for open or laparoscopic surgery.

It is with respect to these and other considerations that the present improvements may be useful.

SUMMARY

According to an exemplary embodiment of the present disclosure, a system for delivering one or more substances into a Fallopian tube of a patient may include a balloon catheter including a tube having a distal end. A balloon may have a first end coupled to the distal end of the tube. A push wire may have a distal end coupled to a second end of the balloon. The balloon may be movable between an inverted position and an everted position by actuation of the push wire. The balloon catheter may be configured to receive the one or more substances such that the one or more substances are retained by the balloon, the push wire, or both, and may advance the push wire to evert the balloon such that the balloon extends distally of the distal end of the tube. In the everted position the one or more substances may be delivered into the Fallopian tube.

In various of the foregoing and other embodiments of the present disclosure, the balloon catheter may receive the one or more substances at the distal end of the tube and the first end of the balloon when the balloon is in the inverted position. The push wire may be hollow, and the one or more substances may be received into the proximal end of the push wire. The balloon catheter may receive a first substance at the distal end of the tube and the first end of the balloon, and the push wire may be hollow such that a second substance may be received into the proximal end of the push wire. The one or more substances may at least partially coat an inner surface of the balloon when the balloon is in the inverted position. The balloon catheter may include a filament attached to the distal end of the push wire, or the second end of the balloon, or both. The filament may be configured to absorb at least a portion of the one or more substances. The filament may be configured to receive a first substance, and the balloon may be configured to receive a second substance different from the first substance. The one or more substances may be at a temperature different than a temperature of the patient. The one or more substances may be any of a radiopaque marker, a radiopaque marking material, a gel, a chemotherapeutic, a fertility therapeutic, an antibiotic, an anti-inflammatory agent, a tissue protecting substance, a dissolvable object, an impermeable object, or a radiation delivering object, or combinations thereof.

According to an exemplary embodiment of the present disclosure, a system for depositing one or more substances in a Fallopian tube of a patient may include a balloon catheter to receive the one or more substances. The balloon catheter may include a tube having a distal end and a balloon having a first end coupled to the distal end of the tube. A push wire for advancement may evert the balloon. The push wire may have a distal end coupled to a second end of the balloon, and the balloon may be movable between an inverted position and an everted position by actuation of the push wire. The one or more substances may be retained by the balloon, the push wire, or both. The one or more substances may be depositable into the Fallopian tube in the everted position of the balloon.

In various of the foregoing and other embodiments of the present disclosure, prior to receiving the one or more substances into the balloon catheter, the balloon may be inflatable in the inverted position by an inflation fluid. The balloon may be evertible such that at least a portion of the balloon may be extended distally of the distal end of the tube. After receiving the one or more substances into the balloon catheter, the push wire may be retractable such that the balloon is re-inverted and positionable proximal of the distal end of the tube such that the one or more substances are retained by the balloon. The balloon may be positionable within a sheath such that the balloon may be extendable from a distal end of the sheath during eversion and may support the balloon during re-inversion. The balloon catheter may include a filament attached to the distal end of the push wire, or the second end of the balloon, or both. The filament may be configured to absorb at least a portion of the one or more substances. The filament may be configured to receive a first of the one or more substances substance, and the balloon may be configured to receive a second of the one or more substances different from the first substance. The push wire may be hollow, and the one or more substances may be received into the proximal end of the push wire. The one of more substances may be any of a radiopaque marker, a radiopaque marking material, a gel, a chemotherapeutic, a fertility therapeutic, an antibiotic, an anti-inflammatory agent, a tissue protecting substance, a dissolvable object, an impermeable object, a radiation delivering object, or a combination thereof.

According to an exemplary embodiment of the present disclosure, a method for depositing one or more substances in a Fallopian tube of a patient may include receiving the one or more substances into a balloon catheter. The balloon catheter may include a tube having a distal end. A balloon may have a first end coupled to the distal end of the tube. A push wire may have a distal end coupled to a second end of the balloon. The balloon may be movable between an inverted position and an everted position by actuation of the push wire. The one or more substances may be retained by the balloon, the push wire, or both. The push wire may be advanced to evert the balloon to the everted position such that the balloon may extend distally of the distal end of the tube. The one or more substances may be deposited into the Fallopian tube in the everted position of the balloon.

In various of the foregoing and other embodiments of the present disclosure, the balloon catheter may receive the one or more substances at the distal end of the tube and the second end of the balloon when the balloon is in the inverted position. The balloon catheter may receive a first of the one or more substances at the distal end of the tube and the second end of the balloon. The push wire may be hollow such that a second of the one or more substances may be received into the proximal end of the push wire. The one or more substances may at least partially coat an inner surface of the balloon when the balloon is in the inverted position. The push wire may be advanced to position the balloon in the everted position prior to receiving the one or more substances in the balloon catheter, such that a surface of the balloon contacting an inner surface of the Fallopian tube in the everted position may be free of a coating of the one or more substances.

DETAILED DESCRIPTION

The present disclosure is not limited to the particular 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 otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure belongs.

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

As described above, performing procedures which require access into the Fallopian tubes without undergoing a surgical procedure may be challenging. Exemplary embodiments of the present disclosure include systems, methods and devices for introducing substances into the Fallopian in a less invasive procedure. Anatomically, the ovaries are in close proximity to the fimbria at the region of the distal opening or distal os of the Fallopian tube. Eggs released by the ovary may be gathered by the fimbria and transported through the Fallopian tube to the uterus. With ovarian cancer, cells may be deposited in the Fallopian tube, which may eventually migrate into the uterus. Cell samples obtained from the uterus may be analyzed to detect ovarian malignancy; however, the incidence of migration of ovarian cancer cells into the uterus may be too low to render uterine sampling a reliable diagnostic test for ovarian malignancy and/or abnormality. Reliable access to the Fallopian tube without damaging the fragile structure, for diagnostic sampling and delivery of substances is therefore desirable.

As described above, the fragility of the Fallopian tube may result in perforation during a medical procedure. As such, safe introduction of a diagnostic device into the Fallopian tube may be difficult with known devices. Referring now toFIG. 1, a Fallopian tube1of a patient may extend from a proximal os3to a uterus, connecting at a uterotubal junction (UTJ)2, to a distal os5and connecting to ovaries6. A perforation may occur at the UTJ2, which is a constriction occurring distal to the proximal os3(e.g., opening) of the Fallopian tube. For example, in some patients the UTJ2may be approximately 1 cm distal of the proximal os3. In some patients, the body lumen size at this constriction may be as small as approximately 0.3 mm or 0.5 mm, while the body lumen size of the Fallopian tube adjacent to the UTJ may be approximately 1 mm. The Fallopian tube is curved, and the soft tissue of the tube is in a naturally collapsed state, which may result in multiple constrictions as passage is attempted. Perforation may occur at the uterotubal junction (UTJ), a constriction that occurs approximately 1 cm distal to the proximal os (opening) of the Fallopian tube in the uterus. The UTJ may present a downward bend in the Fallopian tube. The lumen size of the Fallopian tube adjacent to the uterotubal junction may be approximately 1 mm.

Although systems and devices are described in the present disclosure for accessing a Fallopian tube of a patient, it is understood that the systems and devices may be utilized for other body lumens having challenging navigation, including but not limited to blood vessels, arteries, and other vasculature, ducts, tracts, body lumen, and the like.

Exemplary embodiments of a catheter for introducing substances into a Fallopian tube for minimally invasive procedures may include any of the following: (1) access to the proximal os of the Fallopian tube via an intrauterine approach; (2) advance of an introducer catheter to cannulate the proximal os; (3) use of a second catheter inside the introducer catheter to track inside the Fallopian tube. An inflated balloon at the end of the second catheter is advanced across the proximal portion of the Fallopian tube and is everted further into the Fallopian tube; (4) a substance may be released within the Fallopian tube simultaneously with and/or subsequently to balloon eversion; (5) the surface of the balloon may have a coating that contacts and coats the intraluminal surface of the Fallopian tube, which coating may be a released substance from the catheter; and (6) the balloon may be retracted and removed from the Fallopian tube.

Embodiments of an exemplary catheter may be configured for insertion into the Fallopian tube (seeFIG. 1). Embodiments of the catheter are also described in U.S. patent application Ser. No. 14/764,710, filed Jul. 30, 2015, entitled “Methods and Devices for Fallopian Tube Diagnostics,” U.S. patent application Ser. No. 15/053,568, filed Feb. 25, 2016, entitled “Methods and Devices for Fallopian Tube Diagnostics,” and U.S. patent application Ser. Nos. 15/998,507 and 15/998,501, filed Aug. 16, 2018, entitled “Systems, Methods, and Devices for Fallopian Tube Diagnostics,” which are herein incorporated by reference in their entireties. The Fallopian tube has a curvature (e.g., having a tortuous pathway), and the soft tissue of the tube may be collapsible, thereby resulting in multiple constrictions as passage is attempted. As described above, this may be particularly true at the uterotubal junction (UTJ), which may be muscular and therefore more prone to perforation by insertion of medical instruments. In some patients, the UTJ may also present a downward bend with a lumen size at the constriction that may be as small as approximately 0.3 mm or 0.5 mm, while the body lumen size of the Fallopian tube adjacent to the UTJ may be approximately 1 mm.

In at least one embodiment of the present disclosure, an elongated balloon that is initially inverted into a catheter lumen may be deployable. The balloon may partially evert to enter a proximal end of the Fallopian tube, e.g., the UTJ, thereby cannulating the proximal os. The balloon may evert upon pressurization of the balloon from inside the catheter so that an unrolling mechanism of the eversion creates a path through the Fallopian tube regardless of tortuosity or constriction in the Fallopian tube. In some embodiments, the balloon may evert by a push wire advancement, which may be in concert with pressurization. Up to a great majority of the length of the balloon may be substantially inelastic, such that the balloon does not substantially expand and over-dilate the Fallopian tube as it everts. Balloon expansion may burst or otherwise damage or injure the Fallopian tube. However, exemplary embodiments may also incorporate an elastic distal balloon end expandable to seal the distal os upon retraction of the distal balloon. In embodiments, the device may have a balloon having a sufficient rigidity to cannulate the Fallopian tube and sufficient flexibility for navigation through the tortuous path of the Fallopian tube to minimize potential damage or injury. In some embodiments, the device may include support elements for cannulating the Fallopian tube so that the balloon may not collapse at the proximal os.

Exemplary embodiments of systems and methods of the present disclosure may include positioning, and deployment of, a distal end of a catheter. In some embodiments, a catheter distal end may be deliverable to a proximal end of the Fallopian tube by a hysteroscope. In some embodiments, the hysteroscope may be an exemplary hysteroscope (e.g.,FIG. 2). Regardless of the mode of deployment, a retracted portion of a catheter may be extendable to contact the interior wall of the Fallopian tube. It has been surprisingly found that the act of extending a portion of the catheter may remove a sufficient sampling of cells and/or tissue from the Fallopian tube wall to perform histological and/or cytological evaluation. For example, at least a portion of a length of the balloon may contact the Fallopian tube for sample collection. In some embodiments, a majority of the length of the balloon may be substantially inelastic such that the balloon does not substantially expand and over-dilate the body lumen (e.g., Fallopian tube) as it everts. In some embodiments, the balloon may be sized such that the body lumen does not expand or over-dilate as the balloon everts. As described above, balloon expansion may burst or injure the subject's body lumen. According to some embodiments and as discussed above with regard to the exemplary balloon catheter, the balloon may be extendable by eversion from a catheter only longitudinally into the body lumen such that the balloon does not substantially expand and dilate the lumen as the balloon everts or is extended into the body lumen (e.g., the Fallopian tube). In some embodiments, the balloon may be extendable longitudinally into the body lumen, where a diameter of an inflated balloon may be up to approximately 10-15% greater than a diameter of a Fallopian tube. Radial expansion of the balloon may be limited or controlled by the majority of the length of the balloon being substantially inelastic. It is appreciated that portions of a balloon that are not intended to be inserted within a lumen structure can be elastomeric and therefore may be expandable in diameter and compliant rather than substantially inelastic. Such a hybrid balloon may be well-suited in embodiments when a seal is desired with the UTJ. Exemplary of situations when a seal is desired may include irrigation of the lumen, filling the lumen with an imaging contrast, diagnosing obstructions, and/or topical contact with a therapeutic agent, such as a chemotherapeutic or an antibiotic.

An exemplary embodiment of a catheter, as described below, may be introduced into the uterus of a patient using an operating hysteroscope200, an example of which is shown inFIG. 2. An operating hysteroscope200may include one or more ports. One or more ports may provide irrigation to distend the uterus and allow endoscopic visualization, and port230may provide access to a working channel220which may allow instruments and/or catheters to be advanced distally of the hysteroscope. A proximal introducer catheter10(see, e.g.,FIG. 3) may be advanceable through a working channel of the operating hysteroscope200, and may be used to cannulate the proximal os of a Fallopian tube. A balloon14on the proximal introducer catheter10may be inflated to occlude the proximal os, and the everting sleeve catheter may be advanceable through the proximal introducer catheter10into the proximal portion of the Fallopian tube. The sleeve/balloon element14may be fully everted, and the inflated balloon tip may be pulled back to seal the distal os. Irrigation may be introduced via a port11, and aspirated via the irrigation port11on the proximal introducer catheter10, to collect the sample. Irrigation may also be introduced through both the everting sleeve catheter and the proximal introducer catheter, followed by aspiration through one or both ports (11,13) of the proximal introducer catheter.

Referring now toFIGS. 4A-4B,FIG. 4Aillustrates an exemplary embodiment of a catheter20for delivering a substance to a Fallopian tube, andFIG. 4Bis an expanded detailed view of the distal end ofFIG. 4A. As shown inFIG. 4Aa sheath32may substantially form a cylinder with an open distal end and a proximal end connected to a sheath knob26. The sheath32may be a catheter and may be configured to slide longitudinally along a tube27attached to an operating port10with a Y-connector23for injection of an inflation fluid, such as gas, liquid, or air, or combinations thereof, into the balloon28. In some embodiments, the tube27may be formed of a rigid material, such as metal including stainless steel. A push wire21may be slideably connected to the operating port10and may extend through an O-ring seal22at the center axis of a seal knob24joined to the operating port10. In embodiments, the O-ring seal22may be formed of a silicone material. A conical valve25may act as a seal in the operating port10, e.g., by concentrically surrounding and sealing around the push wire21. A tube29may extend from the operating port10, and may lie within and be concentric to the tube27. In embodiments, the tube29may be formed of a material such as nylon. In the inverted position, the distal end of the tube29may be connected to the leading distal edge of the balloon28, and the proximal end of the balloon28may surround and be sealed to the push wire21, thereby forming a sealed cavity having a substantially toroidal or doughnut shape.

In some embodiments, a suture, or filament30may be extendable from the tip of the push wire21, and may extend through the center of the toroid (doughnut) formed by the inverted balloon28, although embodiments without a suture or filament are also envisioned. The filament30may provide enhanced visibility of the motion of the balloon28during deployment. In some embodiments, markers disposed along the length of the filament30may aid in visibility to the user. The filament30may also improve the ease of insertion of a substance “S” into the distal end. For example, in embodiments where the substance S is delivered via a syringe having a blunt needle tip as described below, the filament30may be used to align the needle tip and guide the tip into the balloon28. The substance “S” may be retained in the balloon in an inverted position prior to insertion in the patient (see e.g.,FIG. 5C), and may be held by an inner surface of the balloon in the inverted position. In some embodiments, surface features on the balloon surface, such as wrinkles, overlaps, or folds, may also aid in retaining the substance “S”. In some embodiments, the balloon may be partially or wholly pressurized to hold the substance “S” in the desired positioned.

FIG. 4Cillustrates a proximal end of the catheter20ofFIG. 4Afor delivering a substance to a Fallopian tube. The push wire21′ may be slideably connected to the operating port10and may extend through O-ring seal22at the center axis of a seal knob24joined to the operating port10. In embodiments, the push wire21′ may include a lumen35extending through the push wire21′, so that the push wire21′ may have a hollow tubular structure. The push wire21′ may define a distal opening36and a proximal opening37of the lumen35. In some embodiments, the outer surface of the push wire21′ may be substantially sinusoidal, and/or have a textured (e.g., non-smooth) surface. A textured surface of the push wire21′ may increase a strength of the long hollow wire, to minimize and/or eliminate potential collapse in response to advancement, and may provide a rack-like surface that can engage with a pawl for fine and precise control and move, which is described in further detail below with respect toFIGS. 11A-11E. The distal end of the balloon28in the everted position may be sealed around the push wire21′ at the distal opening36such that the distal opening36of the lumen35remains unobstructed. The balloon28may remain at least partially in fluid communication with the operating port10forming a sealed cavity with a toroidal or doughnut shape, e.g., as shown inFIG. 4A.

The distal opening36, the lumen35, and/or the proximal opening37may be at least partially in fluid communication with an internal channel formed by a surface of the balloon28that is an inner surface when the balloon28is in an inverted position in the catheter. In embodiments, substances for delivery into the Fallopian tube, including but not limited to markers, gels, chemotherapeutics, fertility therapeutics, or antibiotics, may be injected into the lumen35via the proximal opening37, passed through the lumen35, and dispersed from the distal opening36. When the balloon28is in an inverted position, for example as shown inFIG. 18A, a substance may be dispersed, or ejected, from the lumen35into an internal channel formed by the surface of the balloon28that is the inner surface when the balloon28is in an inverted position. The substance may coat the balloon inner surface, upon which during eversion becomes an outer surface of the balloon (see e.g.,FIG. 16), to contact an inner surface of the Fallopian tube when the balloon is everted. In some embodiments, a substance may be injected into the lumen35via the proximal opening37, passed through the lumen35, and ejected from the distal opening36when the balloon28is in an everted position. When the balloon28is in a fully everted position, for example, as shown inFIG. 18B, the distal opening36of the through lumen35may be extended distally of the distal end of the catheter20. Substances dispersed from the distal opening36of the lumen35of the push wire21′ when the balloon28is in an everted position may be directly applied within the Fallopian tube and directly to the inner surface of the Fallopian tube. This may allow for more precise delivery of substances to a desired location within the Fallopian tube for improved patient treatment.

It is understood that the lumen35and associated components for delivering a substance to a Fallopian tube, as described above with regards toFIGS. 4C and 18B, may also be applied to other exemplary embodiments described herein.FIG. 18Aillustrates an exemplary embodiment of a catheter according to the present disclosure. It is understood that a hollow push wire54ofFIG. 18Amay be incorporated into exemplary embodiments described herein without limitation to the reference numerals used for the various embodiments.

In some embodiments, a split sample of different substances may be deliverable into the Fallopian tube by applying a first substance to the filament30and capturing a second substance with the balloon28. The filament30may absorb, and/or be coated by the first substance, to retain the first substance until delivery in the patient. To minimize cross-contamination of the substances prior to delivery to the patient, the filament may have a length less than a balloon, so that in an inverted position, a distal tip of the filament is proximal to a distal tip of the balloon and/or catheter shaft. To apply a first substance to the balloon surface, the balloon may be at least partially everted up to the distal tip of the suture, so that the inner surface of the balloon is positioned as the outer surface of the balloon, and coated and/or dipped in the first substance. To impregnate the filament with a second substance, the filament may be extended to an exposed position from the balloon to be coated and/or dipped in the second substance. After coating of the first substance on the balloon, and the second substance on the filament, the balloon may be re-inverted, e.g., so that the first substance is disposed on the inner surface of the balloon, and the filament coated in the second substance is disposed within the balloon.

It is understood that when the balloon is everted and re-inverted, the sheath (e.g., sheath32) may provide support to the balloon to minimize and/or avoid kinking or collapse of the balloon. For example, as shown inFIG. 6, when the balloon lacks sufficient support, a portion of the balloon may kink or collapse, which may make it difficult to achieve, or may altogether prevent, reinversion. The sheath may remain stationary during eversion and/or re-inversion, although in some embodiments, the sheath may be movable along its longitudinal axis to extend and/or retract to support the balloon and the received substance during re-inversion.

In some embodiments, the filament may be detached or detachable from the balloon and/or the push rod, e.g., as a separate component. The filament may be separately impregnated and/or coated with a substance and disposed in the balloon for delivery to the patient. When the balloon is everted, the filament may be disposed in the patient, and may be positioned to deliver a drug therapy over an extended period of time. For example, the suture or filament may be impregnated and/or coated with a substance having a delayed or gradual release component. In some embodiments, the filament may be evacuated naturally by the patient (e.g., due to ciliated motion in the Fallopian tube and/or during menstruation), and in other embodiments, the filament may be removable by a medical profession, e.g., via a hysteroscope and graspers.

In some embodiments, inflation fluid for the balloon28may be chilled (e.g., at a predetermined temperature different (lower) than a temperature of the balloon catheter) to a desired temperature to maintain the quality of the substance, e.g., a sperm sample or other treatment substance including temperature-controlled component, prior to injection into the Fallopian tube. For example, a substance may be at a temperature different than a patient to preserve the substance until delivery. In some embodiments, inflation fluid may be warmed (e.g., at a temperature different (above) a predetermined chilled temperature) to help to thaw the temperature-controlled substance, or chilled to maintain the temperature of the temperature-controlled substance, or combinations thereof.

In some embodiments, the balloon28and/or the filament30may be pre-coated with substances that prepare the substance for treatment, prepare the Fallopian tube for receiving the substance, promote sperm motility, or improve the conditions for fertilization within the Fallopian tube, or combinations thereof. Substances that enhance the health of sperm and promote motility illustratively include substances that decrease reactive oxygen species (ROS), Percoll, and Nicodenz. ROS scavengers illustratively include superoxide dismutase (SOD), L-cysteine, and thioredoxin. Substances that enhance the ability of sperm to bind illustratively include Fe2/Asc to introduce lipid peroxidation. In some embodiments, the balloon28and/or the filament30may be pre-coated with antibiotics and/or anti-inflammatory agents, e.g., to act as a drug eluting balloon. For example, the balloon catheter may be utilized for other challenging body lumens, e.g., blood vessel, arteries, and other vasculature, ducts, tracts, body lumens, and the like.

FIGS. 5A-5Eillustrate an exemplary embodiment of a method for capturing and delivering a substance into a Fallopian tube by the catheter20(e.g., seeFIG. 4A). In the exemplary method, an inflation fluid may be introduced into the balloon28, e.g., as shown inFIG. 5Aand as indicated by arrow “A.” In some embodiments, the inflation fluid may be introduced via Y-connector23of the operating port10as a liquid, gas, or air, or combinations thereof, that inflates the balloon28. The inflation fluid may be introduced in the balloon28substantially simultaneously with advancement of the sheath32. The push wire21may be advanceable by a user in a direction as indicated by arrow “C” for everting the balloon28. In some embodiments, the balloon28may be everted such that the balloon28extends distal of the distal end of the catheter. In some embodiments, the sheath may extend with the balloon28during eversion, to receive the substance “S”.

The distal end of the catheter20may be next aligned with a substance “S” to be delivered and may be captured by the balloon28as shown inFIG. 5B. In some embodiments, the substance may be delivered to the balloon and/or filament via injection, coating, and/or dipping. A blunt tip needle may be used for injecting a substance to the inner surface of the balloon. In some embodiments, the balloon may remain in an inverted position so that the substance is injected to the inner surface of the balloon. In some embodiments, the balloon may be at least partially everted before injecting the substance to the inner surface of the balloon. In other embodiments, the balloon may be at least partially everted and the substance may be delivered to the distal tip of the balloon. It is understood that when the balloon is re-inverted, the substance may at least be partially drawn in a proximal direction along the balloon surface.

In embodiments where the balloon and/or the filament is coated and/or dipped in a substance, the substance may be disposed in a container, e.g., a slide or a dish. The balloon may be at least partially everted, and the distal end may be positioned to contact the substance on the slide or dish. The balloon may then be re-inverted, such that the substance is at least partially drawn in a proximal direction on the inner surface of the balloon. It is understood that during re-inversion after capturing the substance, the substance may substantially coat the inner surface of the balloon and/or the filament. In some embodiments, the filament may be impregnated by a substance separately from the balloon by individually coating and/or dipping the filament on a slide or dish containing the substance.

As shown inFIG. 5C, the push wire21may be retracted in a direction as indicated by arrow C′ to pull the captured substance “S” held by the balloon28back into the protective sheath32. The catheter20may be introduced into the uterus and at least partially to the Fallopian tube ostium “FT” (e.g., via hysteroscope) as shown inFIG. 5D.

When the catheter20is in a desired position relative to the Fallopian tube, as shown inFIG. 5E, the push wire21may be advanced in a direction as indicated by arrow “C”, thereby everting the balloon28such that the balloon28is extended into the Fallopian tube. As the balloon28everts, the substance “S” may be dispersed, ejected, or deposited in the Fallopian tube. In some embodiments, the substance S may be advanced out of the catheter20as a result of the balloon being everted, e.g., the inner surface of the balloon in an inverted position is advanced to become an outer surface of the balloon (see, e.g.,FIG. 16).

The method of delivering a substance by the catheter20as well as exemplary embodiments including a lumen35as a hollow tube within the push tube21′ may include introducing the catheter20into the uterus and to the Fallopian tube ostium “FT” (e.g., via a hysteroscope), pressurizing the balloon by a liquid, gas, or air, or combinations thereof, to inflate the balloon28either before or after the catheter20is introduced to the uterus. The push tube21′ may be advanced in a distal direction to cause the balloon28to move between an inverted position and an everted position, for example, as an inner surface advances to a distal end and “unrolls” to an outer surface of the balloon, as shown inFIG. 16. A substance may be injected into the lumen35via the proximal opening37for dispersal out the distal end of the catheter, or via the distal end of the catheter (see e.g.,FIGS. 5A-5E). The substance may be injected into the through lumen35when the balloon is in the inverted position, the everted position, during eversion, or combinations thereof. Substances to be introduced include, but are not limited to, radiopaque markers, radiopaque marking materials (e.g., including markers visible by way of CT scan, X-ray, or MRI scan), gels, chemotherapeutics, fertility therapeutics, antibiotics, protective substances, dissolvable objects, impermeable objects, radiation delivering objects or substances, etc.

When the balloon28is in an inverted position, for example as shown inFIG. 18A, a substance S may be held or stored in at least a portion of the lumen35. In some embodiments, the substance S may be injected into the lumen35from a proximal end of the catheter, or a distal end of the catheter, or both. In some embodiments, a plurality of substances (e.g., “S1”, “S2”, . . . “SN”) may be injected into the lumen35for later dispersal in a Fallopian tube. It is understood that any number “N” of substances “S” may be included. In some embodiments, a first substance (e.g., “S1”) may be injected in the distal end of the catheter. If the first substance is tacky, or more viscous, a blockage may form in the catheter. A second substance (e.g., “S2”) may be injected into the lumen35from a proximal end of the catheter, which may act to lubricate, or to lessen the viscosity, of the first substance, so that both substances may be dispersed in the patient.

In embodiments, the substance S may be dispersed or ejected from the distal opening36of the lumen35into internal channel formed by the surface of the balloon28that is the inner surface when the balloon28is in an inverted position. The inner surface of the balloon may become coated by the substance S, which may contact the inner surface of Fallopian tube when the balloon in everted. For example, it may be desired to coat the Fallopian tube wall with a substance S as part of a treatment procedure or to protect a desired portion of the Fallopian tube wall from further treatment agents. In such a situation, the substance S may be injected into the lumen35when the balloon is in the inverted position. Accordingly, the inner channel of the balloon may be coated with the injected substance. Upon eversion of the balloon, the outer surface of the balloon, now coated in the substance S, may contact desired inner surfaces of the Fallopian tube, thereby transferring the substance S to the Fallopian tube walls for treatment, marking with a marking substance an area of interest, or protecting desired sections of the inner surface of the Fallopian tube, or combinations thereof.

When the balloon is in the everted position, for example as shown inFIG. 18B, a substance “S” may be dispersed or ejected from the distal opening36of the lumen35directly into the Fallopian tube. When the balloon28is in a fully everted position, the distal opening36of the through lumen35is generally the most distal portion of the catheter20. Substances dispersed from the distal opening36of the lumen35of the push wire21′ when the balloon28is in an everted position may be directly applied to the inner surface of the Fallopian tube. This may allow for precise delivery of substances to desired locations in the Fallopian tube.

In some embodiments, methods for delivery of substances to desired locations in a patient's Fallopian tube may be advantageous by minimizing, or limiting, a patient's exposure to a substance S to only desired areas, e.g., an area requiring treatment. For example, for a patient receiving cancer treatments, chemotherapeutic agents may be applied systemically, flushing the body with chemicals that may be harmful to healthy areas of the body. As described above, the catheter20may delivery a chemotherapeutic agent to desired locations in the Fallopian tube while avoiding other targeted areas, thereby potentially minimizing, or limiting a patient's exposure to the chemotherapeutic agent and reducing potentially harmful effects of the substance on otherwise healthy areas of the patient. In some embodiments, a marking substance may be delivered to a desired position in a Fallopian tube. The marking substance may be visible via CT-scan, X-ray, and/or MRI scan, to aid a medical professional in determining positioning in the Fallopian tube.

In some embodiments, the medical professional may desire to mark areas in the Fallopian tube where cell samples have been taken, or where cells are known to be abnormal, malignant, and/or cancerous, so that these desired areas may be monitored and/or treated. In some embodiments, an object may be delivered to a desired location within the Fallopian tube to block, minimize, or prevent spreading of injected/applied substances and/or cancerous cells. In some embodiments, the object may be impermeable. In some embodiments, the object may be bioabsorbable and/or biodegradable. In some embodiments, the object may be deliverable and/or retrievable by the catheter20, e.g., such as an impregnated and/or coated suture or filament as described above. The object may be deliverable during balloon eversion, e.g., as the balloon unrolls. The object in contact with an inner surface of the balloon in the inverted position may be advanced out of the distal end of the catheter for placement in the Fallopian tube.

In some embodiments, a radiation delivering object and/or substances may be delivered to desired locations in the Fallopian tube for radiation treatment. In some embodiments, a dissolvable object such as polylactides may be delivered to a desired location in the Fallopian tube, such that the delivered substances may be released over an extended period of time as the dissolvable object dissolves, or medication is dispersed.

It is understood that exemplary embodiments of the delivery method as shown inFIGS. 5A-5E, as well as delivery via the lumen35in the push tube21′ as shown inFIGS. 18A-18B, may be used independently or in connection with each other, or both, based on the substance or substances to be delivered and the desired location of delivery.

FIGS. 7A and 7Billustrate an exemplary embodiment of a ball tip catheter120in accordance with the present disclosure. A spherical ball122may be attached to the distal end of a spring tip124affixed to a tube, or catheter126. It is understood that “tube” and “catheter”126may be used interchangeably. The spherical ball122may be provided to negotiate through a patient's UTJ to minimize and/or avoid inadvertent penetration through the UTJ sidewalls. The spring tip124may allow the distal end with the ball122to flex around corners and navigate through the UTJ. The spring tip124and spherical ball122may have an open lumen128extendable through the spring tip124and the spherical ball122. The spherical ball122on the spring tip124may be approximately 0.8-1.0 mm in diameter, and the hollow spring tip124may have a length of approximately 1.5 cm and an outer diameter of approximately 0.6 mm. The hollow spring tip124may be formed of a metal (stainless steel or superelastic metal, e.g., Nitinol) coil spring sheathed on the outside with thin walled polymer heat shrink tubing, made of nylon, PET (polyethylene terephthalate), or similar material. In some embodiments, the spring tip124may be a metal coil spring co-extruded into a tubular polymer body. The hollow spring tip124may also be a flexible polymer tube, and in some embodiments may be made of nylon, Polyethylene terephthalate (PET), polyether block amide, or similar materials. An everting balloon130may lie inside the hollow spring tip124. The everting balloon130may extend proximally inside the main lumen132of the introduction catheter126(e.g., a generally flexible tubular structure) or cannula (e.g., a generally rigid tubular structure).

The proximal end of the everting balloon130may be attached to a push rod, or push wire134passable through a seal135on the proximal end of the catheter126or cannula. In operational use on a patient, the flexible ball tip122may be manually advanced through the UTJ. Once passage of the flexible ball tip122and spring tip124through the UTJ occurs, the push wire134may be advanced through the seal135of the previously pressurized introduction catheter126or cannula. Advancement of the push wire134may cause a controlled eversion of the balloon130out of the hollow spring tip124, through the length of the Fallopian tube.

The catheter126described above, and in greater detail below may be introduced into the uterus of a patient using an operating hysteroscope200, an example of which is shown inFIG. 2. An operating hysteroscope200may include one or more working channels. One working channel may provide irrigation to distend the uterus and allow endoscopic visualization, and one or more additional working channels may allow instruments and/or catheters to be advanceable distally of the hysteroscope. The catheter126(e.g.,FIGS. 7A and 7B) may be advanceable through the working channel of the operating hysteroscope, and may cannulate the proximal os of a Fallopian tube. The everting balloon130may be advanced through the proximal catheter126into the proximal portion of the Fallopian tube.

FIGS. 8A-8Billustrate a cross-sectional side view of a balloon catheter, or device,160in accordance with the present disclosure. In some embodiments, a balloon130may have an outer diameter of approximately 0.8-1.0 mm, and may have an initial everted length of approximately 1-3 cm, e.g., approximately 1.2-1.5 cm extending out of the distal end of the catheter126or cannula. The balloon130may be fully evertible into the Fallopian tube, e.g., extending approximately 7-12 cm. The balloon130may be securable to a distal end of the catheter shaft or tube126, as indicated at reference numeral117, and a push wire134, as indicated at reference numeral118. For example, the distal end118of the push wire134may form an end of the balloon130. In embodiments, the balloon130may be bonded to the distal end118of the push wire134. The push wire134may actuate the balloon130from an inverted position in the catheter126to an everted position when an interior of the balloon, between the catheter126and the balloon130and indicated by reference numeral119, is pressurized. In embodiments, an everted position may include at least a portion of the balloon130extending beyond the distal end of the tube126. In some embodiments, the balloon130may be initially partially everted and fixed to the catheter126, forming a rounded end130a. In some embodiments, the balloon130may be inflatable with fluid to a pressure of approximately 14-24 atm (206-353 psi).

The pressurized balloon130may have a rounded end130afor atraumatic cannulation of the proximal os and advancement within the Fallopian tube and a degree of flexibility along the balloon130length. The balloon130may have sufficient column strength to allow the balloon130to be manually advanced through the UTJ, for example, with a push wire134, under at least a partial pressure or no pressure. In some embodiments, the balloon130may be constructed of a thin-walled polymer material, such as polyethylene terephthalate (PET), polyethylene, Nylon, polymer, or a similar material. The balloon130may have a wall thickness from approximately 0.0001 to 0.001 inches and in some embodiments between approximately 0.00019 and 0.00031 inches.

In some embodiments, a first marker171may be disposed on at least a portion of catheter126. The first marker171may be a preparation marker, indicating a desired position of the sheath knob164. When the sheath knob is aligned with the first marker171, the proximal end of the sheath162may be a reference point for the medical professional for balloon extension during preparation and initial cannulation of the balloon130into the Fallopian tube. In embodiments, at least a portion of the catheter126, e.g., a proximal portion connected to the transparent portion167, may be formed of a metal such as stainless steel, or other materials such as composites, or polymers, or combinations thereof. The first marker171may indicate to a user an appropriate location of male luer lock fitting, or sheath knob,164with respect to the balloon130within the sheath162, so that the sheath162may be extended distally an initial length as a preparation step to cover, for example, approximately 10 to 20 mm length of everted balloon130that is used to access the proximal os before the balloon is completely everted.

In some embodiments markers may be incrementally spaced apart in known predetermined distances from each other such that a medical professional may use the markers as a visual counter or measuring device to verify an approximate length of balloon that has been everted. It is appreciated that any inner cannula or catheter described herein may include indicia as described for assistance in navigating patient anatomy.

In some embodiments, a second marker173may be disposed on the catheter126, e.g., a metal portion138, to indicate a desired location of sheath knob164to confirm that the sheath162covers the deployed everting portion (balloon, filament, etc.) during device removal into the hysteroscope200. For example, the second marker173may be a retraction marker. This may allow the user to visualize and confirm that the balloon130is fully protected by the sheath162during the removal process to avoid loss of cells collected on the balloon and/or extended portion. When the hysteroscopic view is obscured, for example, by blood or tissue in the distension fluid, additional user visualization by the second marker173may be advantageous. The second marker173may be formed by the same techniques used to form the first marker171. The second marker173may also be included on any inner cannula or catheter described herein.

In some embodiments, the balloon material may be treated to change the surface properties of an exterior surface of the balloon130. Processes such as plasma or corona treatment may increase surface receptiveness to various substances that illustratively include subject cells, inks, coatings, adhesives, laminates, and paints, or combinations thereof. Surface treatment may enhance wettability creating a surface with hydrophilic properties, or discourage wetting creating a surface with hydrophobic properties. Surface treatment may be used to improve the adhesion properties of the balloon surface, to create a surface in which cells are more likely to adhere compared to an untreated surface.

Surface treatments may also be used to prepare the balloon surface for printing indicia on the surface, e.g., including PAD printing. PAD printing (also called tampography) is a printing process that may transfer a 2-D image onto a 3-D object. Indicia printed on the balloon surface may serve as preparation markers for the user. These preparation markers may allow the user to know the length of the balloon130prior to deployment of the balloon130, thereby improving the ease of use of the device by eliminating the need for an outside measuring tool and improving the safety of the procedure by eliminating any guesswork or eyeballing on the part of the user.

In addition to marking for visualization purposes, the balloon130may also be treated with a process that increases surface area such as the application of a nanofiber or micropillar surface (e.g., including but not limited to ULTRA-WEB® from Corning), which may improve cell collection yield and/or retention compared to a balloon with little or no surface treatment. The filament, suture, or string121may include similar surface treatment features as a way to enhance cell collection and retention.

The balloon130may be translucent, optically transparent, or a combination thereof. In some embodiments, the balloon130may 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 color of the balloon and to further enhance visibility of the balloon. The amount of the opaque fluid added to the inflation fluid may control the level of translucence or opacity of the balloon. In some embodiments, the fluid may be rendered opaque or otherwise detectable through the inclusion of colloidal or suspended particulate or microbubbles released within the fluid. Colloidal or suspended particulate operative herein include without limitation, polymethylmethacrylate, mica, barium sulfate, starch, and combinations thereof.

The length of the fully everted balloon130may extend to approximately 7-12 cm within the lumen (e.g., Fallopian tube), such that when fully everted, the balloon130may extend within the patient's Fallopian tube, following the successful advancement of at least a portion of length of everted balloon through the UTJ. Eversion of the balloon130may be performed in a controlled manner, e.g., by advancing a push wire134through a fluid tight seal135, at the proximal end of the catheter126. As described above, at least a portion167of the catheter126may be transparent or translucent, so that movement of the balloon130may be viewable through the hysteroscope through which the catheter126is inserted, thereby providing the user with a direct view of the insertion procedure. The catheter126may be constructed of polymers such as Nylon, polyether block amide, polyurethane, PET (polyethylene terephthalate), polyethylene, or polyvinyl chloride (PVC), with or without polymer or metal coil or braid reinforcement, or combinations thereof.

In some embodiments, a balloon130, when everted at least partially out of the catheter126or cannula, may not remain straight. Rather, the balloon130may assume an undesired curved configuration, either a single “C” curve, or an “S” curve, that may be difficult to use to cannulate the proximal os of the Fallopian tube, and to advance the balloon through the UTJ. The extended length of everted balloon130may be straightened out or maintained straight by use of an outer sheath162that lies coaxial about the exterior of catheter126or cannula, and may assist in providing column strength and cover of the partially everted balloon tip. At least a portion of sheath162and/or catheter126may be transparent167, e.g.,167ofFIG. 8A, so that movement of the balloon130may be viewable through the hysteroscope through which the catheter is inserted, thereby providing a user with a direct view of the insertion process. Similar to catheter126, the sheath162may be constructed of polymers such as Nylon, polyether block amide, polyurethane, PET (polyethylene terephthalate), polyethylene, or polyvinyl chloride (PVC), with or without polymer or metal coil or braid reinforcement, or combinations thereof. The sheath may be alignable with respect to the catheter and/or the balloon, thereby providing column strength to the balloon. In response to cannulation of the balloon through the UTJ into the Fallopian tube, the sheath may support the balloon from outside of the proximal os of the Fallopian tube to minimize and/or prevent collapse as the balloon is further everted after navigating the UTJ. The sheath162may also protect the sample (e.g., cells) collected on the balloon and/or extended portion. For example, the sheath162may protect the balloon in an everted position after contacting an inner surface of the Fallopian tube. In some embodiments, the sheath162and balloon with or without extended portion may be retracted coaxially with the inner lumen of the sheath to extend the sheath over the everted balloon, and extended portion, if included, subsequent to cell collection. In some embodiments, the sheath162may remain stationary relative to the balloon130and/or the catheter126, so that the balloon130is received in the sheath162subsequent to cell collection. As the balloon130is withdrawn into the sheath and removed from the patient, the sheath may protect the cells to minimize and/or prevent loss of the sample collection by providing a barrier from distention fluid in the uterus or irrigation fluid in the Fallopian tube or uterus. For example, the balloon subsequent to cell collection may otherwise be exposed to environmental conditions that may render the sample collection unusable, and/or otherwise wash the cells from the balloon and extended portion.

FIG. 16illustrates an exemplary embodiment of a linear eversion of a balloon130in accordance with the present disclosure. In embodiments, one end of the balloon may be fixed to inner cannula/tube at point X (e.g., reference numeral117as illustrated inFIG. 8A) and the other end of the balloon may be movable at point Y (e.g., reference numeral118as illustrated inFIG. 8A). The balloon130may evert from the position shown in Step1to the position shown in Step2to the position shown in Step3. In the eversion process, points A, B, and C move towards the left side of the diagram, e.g., extend distal of the distal end of the device160. As the balloon130unrolls/everts at/toward the left side of the diagram, point A may move from the inside surface of the balloon to the outside surface. In practice, the balloon130that has been partially, or initially, everted during the preparation step may be advanced further into the proximal end of the Fallopian tube. Further eversion (extension) of the balloon (in total up to the full length of the Fallopian tube, approximately 7-12 cm) may be accomplished by further rotation of a drive wheel204(seeFIG. 10). The balloon130may then be deflated by relieving pressure in the inflation device. The balloon130may then be retracted from the Fallopian tube. Because the Fallopian tube is a potential space, the Fallopian tube tissue may tend to collapse around the balloon. Because the balloon fills the Fallopian tube, the balloon surface area may be substantially equivalent to the surface area inside the Fallopian tube. This surface area may optimize tissue collection from the inside of the Fallopian tube. While deflation of the balloon may be desirable prior to retraction, it may be possible in some embodiments to retract a balloon/extended portion from a Fallopian tube without first deflating the balloon and still retaining cells collected thereon. For example, the balloon130in an inflated and/or a deflated state may be retracted within the sheath162while retaining a sufficient amount of cells on the surface of the balloon130for testing. Alternatively, the balloon may be repeatedly inflated and deflated while extended in the Fallopian tube, so that each time the balloon contacts Fallopian tube walls, more cells may be collected and/or retained by the balloon.

In some embodiments, to further aid tissue collection, wrinkles or other surface features may be added to the surface of the balloon. Wrinkles may form as the balloon deflates to create multiple edges and/or overlapping material, to aid in cell collection. Edges may work in a manner similar to the edges of a curette or edges of jaws in a biopsy forceps. Similar to these features on other collection devices, edges formed by the wrinkled balloon may focus a contact force on the anatomical wall in order to collect cells.

The balloon deployment device in accordance with the present disclosure may then be removed from the working channel of the hysteroscope and from the patient. Once the device is removed from the patient, cells may be removed from the balloon by dipping the balloon and/or the extending portion (if used) into a cytopreservative and stirring in order to agitate the cells. Alternatively, balloon, extending portion, and/or sheath may be cut off and placed into a cytological preservative. In some embodiments a sheath may be extendable and deployable over the balloon as the balloon is deflated and removed to protect tissue samples collected on the balloon surface.

FIG. 9illustrates a cross-sectional side view of a balloon catheter160′ including a superelastic push rod, or a push wire175and spiral carrier176. The spiral carrier may minimize and/or eliminate the need to extend the push wire backwards, e.g., outside of a handle, for the full length of the push wire in accordance with embodiments of the disclosure. The push wire175may be constructed of a superelastic material such as Nitinol (nickel-titanium compound) wire. At least a portion of a length of push wire175may be coiled into a spiraling tubular carrier176, which may be made of polyethylene or polytetrafluoroethylene (Teflon). The outer spiral diameter of the carrier may be approximately 8 cm, rendering the proximal operating length of the catheter handle much more compact. The spiral carrier176may be attached to a proximal seal135on the catheter by a flexible strap177. In some embodiments, the flexible strap177may be constructed of polymer or silicone rubber material. In some embodiments the push wire175may have a diameter of approximately 0.025″, or some other thin diameter, which may be disadvantageous for purposes of gripping the wire and push it forward through the seal135. A flexible grip178may be included that slides freely on the push wire175, but upon compression between the thumb and forefinger, may provide a grip for push wire175advancement. The flexible grip178may be an elliptical cross-section frame that may be made of polyvinyl chloride, silicone rubber, or combinations thereof, or similar flexible compound. In some embodiments, the flexible grip may have inner dimensions of approximately 2 cm in length, 1 cm in width, and 3 mm in height, and may have a wall thickness of approximately 2 mm. Holes in the proximal and distal faces of the grip may be a slip fit with the push wire175.

FIG. 10illustrates an exemplary embodiment of a balloon catheter200configured with handle202. In embodiments, the handle202may be included in the device160as illustrated inFIG. 8A. The handle202may house a gear mechanism220(seeFIGS. 11A-11B), also referred to herein as an actuator. The handle202may be in mechanical communication with a push wire134,206and may control actuation of the push wire134,206, which in turn may control actuation of the balloon130between an inverted position and an everted position. Handle202may include a drive wheel204for advancement and retraction of the push wire134,206, in which the balloon130may evert linearly (e.g., gradually unfold or unroll from the inside out.). The drive wheel204may be made of polymer material including but not limited to ABS. The outer edge of the drive wheel204may include notches, or a knurl pattern, to facilitate gripping the wheel during operation of the catheter200. The outer edge of the drive wheel204may include multiple features shaped like arrow heads that facilitate gripping and/or may indicate correct direction of travel of the drive wheel. A top surface of the drive wheel204may have an arrow molded into it for indication of a correct direction in which to turn in order to evert the balloon. The opposite side of the drive wheel204may include a square boss222insertable into a drive gear224. In some embodiments, the gear mechanism220may include a step-down gearing that provides a reduced amount of extension of the push wire134,206relative to a given rotational distance travelled by the drive wheel204(i.e., the drive wheel204must be turned more of a distance to accomplish the same extended length of balloon everted, than if step-down gears were not included or a different ratio of step-down was included). The resultant effect may be to have a finer control over the eversion of the balloon130as the drive wheel204is turned.

The catheter200may retain the balloon130in a shaft210(which may at least partially be formed of a stainless steel tube and/or a Nylon tube), a sheath212, and/or a sheath knob214. For balloon advancement, the balloon130and shaft210may be pressurized with an inflation device (such as inflation device172ofFIG. 8C) that is attachable to an extension tube168,216, or to luer218, of the handle202(seeFIGS. 11A-11B). In some embodiments, luer219may be attachable to the extension tube168,216. In some embodiments, the push wire206may extend proximally from the handle202and may include a luer219′. The push wire206may be hollow, thereby allowing for delivery of one or more substances through the device to a desired tissue location. In some embodiments, the push wire may include a single tube, connecting a balloon at a distal end and a luer at a proximal end, such that one or more substances may be easily and efficiently delivered to a desired tissue location.

Once the catheter device200is pressurized, a user may rotate the drive wheel204causing a push wire134,206to advance. Although in some embodiments, the balloon130may evert under pressurization without a drive wheel advancement of the push wire134,206, it is understood that the drive wheel may allow for smooth, slow, controlled advancement of the balloon, thereby minimizing or avoiding potential perforation of the Fallopian tube. The sheath knob214may allow the sheath162,212to be used as an introducer as the sheath162,212locks onto the body of the catheter126,210. The sheath knob214may be compliant enough to allow the user to move the sheath162,212when needed, for example to the pre-extended portion of the balloon and to move the pre-extended portion of the balloon into the Fallopian tube. In embodiments, the sheath knob214may be tight enough such that unintended balloon or catheter movement may be minimized and/or prevented.

FIG. 11Ais a cross-sectional view of the handle portion ofFIG. 10, andFIG. 11Bis a detail view of an exemplary embodiment of an internal handle gear mechanism220in accordance with the present disclosure. The handle202may also have an extension tube168,216that is attached to a luer218in the handle body, e.g., for attaching one or more additional tools or devices such as inflation device172(see alsoFIG. 8C). The gear mechanism or actuator220may be in mechanical communication with the push wire134,206, and may control actuation of the push wire134,206, which in turn may control actuation of the balloon130between the inverted position and the everted position. In some embodiments, the gear mechanism or actuator220may include a plurality of gears operating enmeshed to have a step-down ratio. According to various embodiments, the handle gear mechanism220may include a drive wheel204, which allows controlled actuation of the gear mechanism220and single user operation.

In some embodiments, to provide feedback to the physician regarding the end of balloon deployment, the internal handle gear mechanism220or actuator may include a limit mechanism on the gears for limiting the advancement of the push wire and/or a unidirectional balloon movement. In some embodiments, the limit 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-click in mechanism. At a predefined maximum extension, a pawl242may engage with one or more gears (e.g., gears224,228,230,232) as shown inFIG. 11E, to form a gear jam. The pawl242may be activated to stop further advancement of the balloon130. In embodiments, the pawl242may be any mechanism configured to engage with one or more gears. For example, at a predefined push wire extension, the pawl242may rotate around a pivot point to engage with one or more gears, causing a jam and preventing further rotation. Alternatively, a rack and pawl gear, a linear gear, or a drop key-click-in mechanism (FIG. 11D) may be employed to stop advancement of the balloon and in some embodiments may be disposed in the handle (seeFIG. 11A, detail “F”). Referring toFIG. 11C, an exemplary ratchet mechanism for linear motion is shown. Ratchets are mechanisms that serve to limit motion to only one direction. A ratchet may have three main parts: a linear gear rack233, a pawl235(e.g., a “click”), and a base or mount237. The edges on one side of the teeth239,239′ on the linear rack may have a steep slope while the other edges of the rack's teeth may have a moderate or gradual slope. For example, edges on one side of the teeth239,239′ may be steeper than edges on another side of the teeth239,239′. In some embodiments, a steeper slope may have an angle of approximately 60°-90°, e.g., as indicated at239b,239b′, and a more moderate slope may have an angle of approximately 10°-50°, e.g., as indicated at239a,239a′. The pawl235may contact the linear gear rack233. When the linear rack is linearly moved in a first direction, the pawl235may slide over the teeth239without restricting the natural motion of the device. When the direction of motion is reversed to a second direction, the pawl235may contact the steep slope on the gear tooth239to impede motion. The pawl235may be biased downward by a spring into the linear gear rack233. In some embodiments, a spring, e.g., a torsional spring, may be disposed at a pivot point236, e.g., at a first end of pawl235, for pivotable rotation of the second end of the pawl235. In some embodiments, a spring, e.g., a linear spring, may be disposed at a second end of the pawl235, as indicated by reference numeral223, to bias the pawl235towards the gear teeth239. The linear gear rack233and pawl235may be typically mounted in a fixed relationship to one another on a mount237, with the rack sliding in relation to the mount and the pawl235having a pivot connection to the mount. In some embodiments, the device may include a manual knob or push button switch to overcome the spring bias on the pawl235to allow for the lifting of the pawl235from the set of teeth on the linear gear.

A limit may be set on the ratcheting action of the linear gear rack233in the gear mechanism220ofFIGS. 11A-11Bto set a limit on the advancement of the push wire206, e.g., as shown at “F”. During advancement of the push wire206, a pawl238may be biased toward from linear gear rack233as shown in detail “F” ofFIG. 11A. In some embodiments, the pawl238may be pivotal about a point, as indicated by reference numeral221. Linear gear rack233may be directly attached to the end of the push wire206away from the balloon130in the handle202. Advancement of the push wire206may be automatically stopped when pawl238meets stop243, which may be greater in height than teeth239′. A manual knob or push button switch205as illustrated inFIG. 10may be actuatable by a user to overcome a spring bias on the pawl238to allow for the lifting of the pawl238from the linear gear rack233and for retraction of the push wire206and the attached balloon130. InFIG. 11D, in another embodiment different from the ratcheting action of the linear gear rack233, the push wire206may be continuously and smoothly advanced and coiled around deployment wheel245until pawl235reaches and engages with detent247to stop further advancement of the balloon130. InFIG. 11E, the pawl235may act as a gear jam when an extension limit of the balloon130is reached.

The sequence of steps used to enter and track through the Fallopian tube may be described with the embodiment ofFIG. 8A. When it is desired to cross the UTJ with a length (e.g., approximately 15 mm) of an everted balloon130, the outer sheath162may be placed in apposition with the proximal os of the Fallopian tube, without entering the proximal os. The outer sheath162may support the initial length of everted balloon130until it enters the proximal os. A portion of the balloon, e.g., a short length, of pressurized everted balloon130exiting the supportive outer sheath162may have sufficient column strength to be manually advanceable through the UTJ, whereas an unsupported length (e.g., without the sheath) of the everted balloon130may not contain sufficient rigidity by itself. As such, an everted/everting balloon130may buckle upon attempted advancement through the proximal os and UTJ without a sheath. In some embodiments, crossing the UTJ with a length of the everted balloon (e.g., 15 mm), may occur. This initial cannulation length may support keeping the Fallopian tube open even if a spasm occurs, which may occur in this area of the Fallopian tube. It is also understood that other cannulation lengths may be utilized to maintain an open Fallopian tube.

In some embodiments, the sheath162may be compatible with standard hysteroscopes having a working channel, e.g.,5F. A sheath162may be used in an exemplary system as a balance to provide a wall thickness great enough to impart sufficient column strength to the sheath and thin enough to maintain a sheath inner diameter large enough to accommodate the balloon130. This balance may improve cell collection efficiency, e.g., by having an inner diameter sufficient to retain the balloon130without inadvertently removing (scraping) cells from the balloon surface. It is understood that the balloon130may be retained within the sheath162in an inflated state and/or a deflated state.

As mentioned, a male luer lock fitting, or sheath knob,164including a Tuohy-Borst seal136connector may be included at the proximal end of the sheath162. A Tuohy-Borst adapter that includes seal136is a medical device used for creating seals between devices and attaching catheters to other devices. The Touhy-Borst seal136may be tightened to have a slip fit with the catheter or cannula holding the sheath162in place. The sheath knob164may mate with a female luer lock fitting, if present, at an instrumentation port, on the working channel of the hysteroscope200. Referring back toFIG. 2, the male luer lock or sheath knob164may be connectable to the instrumentation port230so that the catheter126and/or sheath162may move with the hysteroscope200. In some embodiments, the instrumentation port230may further include a seal for the catheter126to extend through. When these respective luer fittings are connected, the tip of the sheath162may protrude out of the distal end of the hysteroscope, e.g., approximately 2-3 cm. The sheath162may also protect a portion of a balloon130everted during device preparation (e.g., a length approximately 1.5 cm) from injury as the catheter126is advanced through the working channel of the hysteroscope. A stainless steel tube, e.g., hypotube138, may be at least a portion of the inner cannula126to provide sufficient rigidity and/or column strength to minimize or prevent kinking or collapse of a portion605protruding from the proximal end of the hysteroscope working channel, as shown inFIG. 6. In some embodiments, the hypotube138may be sized having approximately 0.050″ OD×0.004″ wall thickness for sufficient rigidity.

FIG. 8Cillustrates a balloon catheter160ofFIG. 8Awith a tubing reservoir, or extension tube168, and inflation device172in accordance with an exemplary embodiment of the disclosure. It is understood that in some embodiments the extension tube168may be similar to extension tube216as shown inFIG. 11A. The extension tube168,216may be configured to withstand pressurization. Pressurization of the balloon130by fluid injection may be performed using a syringe device, such as the exemplary inflation device172. Rotation of a threaded plunger shaft through a releasable lock may increase and maintain pressure in the inflation device172, while a pressure gauge174provided with the inflation device172may allow for control of input pressure. In some embodiments, the balloon catheter160may provide for a one-person operation of the device. A length of pressure tubing, or extension tube168,216, may be added between the inflation device172and the inflation port166on the device. The extension tube168,216may be constructed of polymers such as polyurethane or polyvinyl chloride (PVC), with or without polymer or metal coil or braid reinforcement. The extension tube168,216may contain an amount of intrinsic elasticity, while the everting balloon may be generally inelastic. At full pressurization of the balloon130, the extension tube168,216may impart a fluid capacitance to the system. A small volume of fluid may be containable in the everted balloon, and this volume may be further subtracted by the volume occupied by the push wire134(e.g., which moves into the balloon130as it is being everted). The resultant everted balloon volume may be small compared with the larger volume in the pressure tubing168, which may allow the balloon130to evert to its full length without significant decrease in pressure, once the balloon catheter160has been pressurized.

As described above with respect toFIGS. 8A-8C, the everting balloon130may be extendable a total distance of approximately 7 cm distal to the tip of the catheter, in order to pass through the entire length of the Fallopian tube. The everting balloon130may form a toroidal shape at the end130aas it exits the catheter tip, and the everted portion may include a double walled configuration. A toroidal shape may be an atraumatic shape for minimizing or avoiding damage during extension into the Fallopian tube. Thus, for example, the push wire134advances forward a distance of approximately 14 cm in order to yield an everted balloon length of 7 cm. This length of push wire may initially extend backwards from the proximal end of the catheter126, directly into the face of the operator, making its use cumbersome. The push wire may also be susceptible to contamination of the sterile device due to its length as it may extend into a physician's working space during a procedure. For example, the proximal end of the long push wire134may contact the physician's face or surgical mask during use. Therefore, it may be desirable to provide a push wire system that does not have to extend backwards for the full length of the push wire134. The superelastic push wire175and carrier design ofFIG. 9and the balloon catheter200configured with handle202ofFIG. 10may contain the push wire and minimize and/or avoid the need to extend the push wire back towards the user.

FIG. 12illustrates a cross-sectional side view of an exemplary everted balloon catheter180including a tube182having diameter smaller than the inflated diameter of the everting balloon130for insertion into the patient's UTJ in accordance with the present disclosure. The tube182may straighten a portion of the balloon tip163. In some embodiments, the tube182may extend distally to the tip of the cannula. In embodiments, the tube182may have an approximately 0.0005″-0.001″ wall thickness (e.g., being a “thin-walled” tube), and may extend approximately 1.5 cm distal to the tip of the cannula. The tube182may have a thickness and resiliency sufficient to support the balloon130, to maintain a position of the balloon tip163(e.g., maintain a straight position). In some embodiments, the tube182diameter may be smaller than the balloon130diameter, so that the balloon130may retain flexibility and compressibility. This flexibility may be beneficial to allow the balloon130to be advanced through the UTJ. In some embodiments, the balloon130may include the tube182to support and/or straighten the balloon. In embodiments, the tube182may have a 0.033″ OD×0.001″ wall×1.5 cm long.

FIG. 13illustrates a cross-sectional side view of an everted balloon catheter190including one or more flexible polymer monofilament string and/or filament192as an extending portion attached to the distal end of the cannula or catheter126. The strands192may extend into everting balloon163, thereby supporting and keeping the tip straight for insertion into the patient's UTJ in accordance with an embodiment of the present disclosure. In some embodiments, the one or more flexible polymer monofilament string and/or filament192may extend into the balloon163(e.g., approximately 1.5 cm). The monofilament192may be formed of nylon, polypropylene, or other flexible polymer material, or combinations thereof. The monofilament strands may have a diameter of approximately 0.006″-0.012″. In some embodiments, the balloon130may have approximately a 0.033″ (0.8 mm) OD with a 0.008″ diameter monofilament192inside an approximately 1.5 cm long everted balloon tip.

In embodiments, a portion of the everted balloon may be treated with fluoropolymer, silicone, and like material coatings, or combinations thereof, lubricating the surface at the lead portion of the balloon catheter, which may enter the constricted portions of the Fallopian tube (e.g., the UTJ).

FIG. 14illustrates a cross-sectional side view of a balloon catheter280configured with striped balloon130S in accordance with an exemplary embodiment of the present disclosure. As shown inFIG. 14, the indicia131of the striped everting balloon130S may be coupled with a transparent distal section167of the cannula or catheter126to provide visual feedback of balloon eversion. In some embodiments, the indicia may be pad printed or scribed with an indelible marker in a highly visible color. In some embodiments, the indicia131may be approximately 1 mm wide, spaced approximately in 0.5 cm increments along the entire length of the balloon. Pad printing (also called tampography) is a printing process for transferring a 2-D image onto a 3-D object. Other patterns may be used instead of, or in addition to, indicia131on the surface of the balloon130S. For example, indicium131on the balloon130S may be spaced apart (e.g., approximately 0.5 cm), and dots may also be added in the remaining intervals between the indicia131. Each indicium131that comes into view in the transparent distal section167may indicate a successful eversion of a length of a balloon130S (e.g., 0.25 cm, as the push wire is advanced approximately twice the length for a corresponding approximate length of balloon eversion (e.g., 0.5 cm). Indicia131of different thicknesses may be used, as well as different colored indicia, or a different number of indicia, or combinations thereof, in the same fashion described for the stripe and dot combination. In some embodiments, color coded sections may be added to the balloon130S to indicate the extent of the balloon eversion.

Additional embodiments of feedback markers, which may be externally visible to the physician on the outside of the patient's body, for the extent of positive balloon eversion. In some embodiments, a knotted string or suture as an extending portion may be adhered to the distal end of the push wire or tip of the balloon, and may be spaced in known increments to provide tactile feedback as to balloon eversion progress. The knotted string or sutures may allow for visualization of the forward movement of the balloon as it is everted. The knotted string or sutures may be radio opaque. In some embodiments shown inFIG. 15A, a string140may be pad printed with indicia131in a similar manner to the balloon as noted above inFIG. 14,FIG. 15Billustrates a string140′ with a series of knots or sutures142. The balloon130may be at least partially transparent to enhance visibility of string, indicia, knots, or sutures.

Additional feedback mechanisms may include filling the balloon130with agitated saline and visualizing air bubbles with ultrasound, and a sinusoidal pattern for the balloon, where the distances between maximums of a sinusoidal wave define an incremental distance of balloon eversion.

Navigation within the Fallopian tube and the indication of a clear path or obstructions may be provided by release of microbubbles from the tip of the balloon or from the distal end of the tube that the balloon everts from. Travel of the microbubbles may be trackable using imaging, such as ultrasound, to ascertain where a clear path exists. In instances of an obstruction251, e.g., an occlusion or a constriction, the microbubbles may bunch up, or congregate, when the microbubbles are impeded. In response to detecting a grouping of microbubbles, a medical professional may be able to ascertain an obstruction.FIG. 17Aillustrates a release of a stream of microbubbles249from a tip of the balloon130in the Fallopian tube1where no constrictions or obstructions are present, as evident by the steady continuous line of microbubbles249. In some embodiments, microbubbles may be delivered through a lumen54of a balloon, as shown inFIGS. 18A-18B. The frequency or spacing of the microbubbles249may be controllable for finer measurements than with an air source that is modulated on or off, where the air is introduced to the fluid injected into the balloon130.FIG. 17Billustrates a Fallopian tube1with a tubular constriction or obstruction251, where the tubular constriction or obstruction251may impede a flow of microbubbles249and the microbubbles249begin to congregate, or bunch up, at the point of the constriction or obstruction251. The bunching of the microbubbles249may provide a visual indication to the user where the constriction or obstruction251is in the Fallopian tube1. In response to a detected obstruction251, a medical professional may perform additional imaging, such as ultrasound, to determine where the balloon stopped.

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