Devices for fallopian tube diagnosis

Abstract

To provide a device for diagnosing a fallopian tube by a low invasive method.SOLUTION: A catheter for fallopian tube diagnostics includes a tube (10) having a distal end and capable of positioning a fallopian tube (1), and balloons (12 and 14) each having a proximal end and a distal end. The balloon is connected to the distal end of the tube, at the proximal end of the balloon, and is movable between a first position where folded back and a second position where folding-back is undone, and thereby, the balloon can extend to the second position where folding-back is undone in the fallopian tube. The catheter further includes a push wire (206) attached to the balloon and an actuator (220) controlling advancement of the push wire for returning the folding-back of the balloon in a controlled manner when applying the pressure.SELECTED DRAWING: Figure 26A

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Application No. 15 / 053,568, filed February 25, 2016, the contents of which are incorporated herein by reference.

[0002] The present invention relates generally to fallopian tube diagnostics, and more particularly to catheters and diagnostic acquisition devices that address the anatomical challenges associated with navigation within the fallopian tubes. [Background technology]

[0003] Ovarian cancer is a serious disease among women, with one in 72 women in the United States being diagnosed with ovarian cancer during their lifetime. In 2012, 22,280 women in the United States were diagnosed with the disease, and 15,500 women died from this malignant tumor. Ovarian cancer is highly lethal due to the lack of any clear early detection or screening tests for this type of cancer, meaning that most cases of ovarian cancer are not diagnosed until they reach an advanced stage. Therefore, ovarian cancer screening is of high clinical interest because the disease is generally not detected in its most curable early stages.

[0004] Currently, definitive detection of ovarian cancer requires a surgical procedure to obtain a cell sample for diagnosis. Because the ovaries are located within the abdominal cavity, laparoscopic or open surgery (laparotomy) is required to access the ovaries for evaluation. Furthermore, ovarian biopsies are generally not recommended in clinical practice guidelines due to the risk of further spreading of the cancer.

[0005] Anatomically, the ovaries are located adjacent to the fimbriae, which are located in the region of the distal opening of the fallopian tubes. Eggs released from the ovaries are collected by the fimbriae and transported through the fallopian tubes to the uterus. In ovarian cancer, cells may be deposited in the fallopian tubes, and some of these cells may find their way into the uterus. While cell samples obtained from the uterus can detect ovarian malignancies, the incidence of ovarian cancer cell migration to the uterus is too low to provide uterine sampling for reliable diagnostic testing for ovarian malignancies. More ovarian cancer cells migrate to the fallopian tubes, and this number increases in the distal portion of the fallopian tubes, near the distal opening. The ability to examine cells in the fallopian tubes for malignancies, if possible without the risk of spreading cancer cells, would be of considerable clinical value for the early detection and treatment of such cancers. Additionally, there is a need to distinguish ovarian cancer from fallopian tube cancer based on the detection of abnormal cells in the fallopian tubes for several reasons, including the different treatment plans between them.

[0006] However, the introduction of diagnostic devices into the fallopian tubes is problematic because the tubes are very fragile and prone to perforation during passage of most devices. Such perforations typically occur at the uterotubal junction (UTJ), a narrowing that occurs approximately 1 cm distal to the proximal opening of the fallopian tube into the uterus. The luminal size of this narrowing is as small as 0.3 mm or 0.5 mm, while the luminal size of the fallopian tube adjacent to the UTJ is approximately 1 mm. Figure 1 shows a cross-sectional view of a fallopian tube 1, which connects the uterus 4 to the ovaries 6. The fallopian tube 1 has a uterotubal junction (UTJ) 2. Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, there is a need for devices and processes that allow for obtaining cell samples from the fallopian tubes for evaluation of ovarian cancer in a minimally invasive manner, particularly without the need for skin incisions. Additionally, there is a need to obtain representative cell samples from the fallopian tubes using a catheter to screen for early stage cancer. [Means for solving the problem]

[0008] Disclosed are methods and devices for performing minimally invasive procedures useful for fallopian tube diagnosis. In at least one embodiment, the proximal opening of the fallopian tube is accessed via an intrauterine approach, an introducer catheter is advanced and cannulated to form a fluid-tight seal with the proximal opening of the fallopian tube, a second catheter inside the introducer catheter is advanced down the length of the fallopian tube and out into the abdominal cavity, a balloon on the end of the second catheter is inflated and the second catheter is retracted until the balloon seals the distal opening of the fallopian tube, irrigation is performed substantially down the length of the fallopian tube, and the irrigant is collected for cytology or cellular analysis.

[0009] The present invention is described in detail below with reference to the following non-limiting specific embodiments of the invention, and the claims should not be construed as being limited to the particular devices detailed. [Brief explanation of the drawings]

[0010] [Figure 1] 1 is a cross-sectional view of the fallopian tubes, which connect the uterus to the ovaries and have the uterotubal junction (UTJ). [Figure 2A] 1A-1C are schematic cross-sectional side views illustrating the sequence of insertion of a particular embodiment of a catheter of the present invention into a tubal insertion catheter, sealing the end of the fallopian tube. [Figure 2B] 1A-1C are schematic cross-sectional side views showing a sequence of insertions of a particular embodiment of a catheter of the present invention into a fallopian tube insertion catheter, where a catheter with a folded sleeve is inserted through the insertion catheter and into the fallopian tube. [Figure 2C] 1A-1C are schematic cross-sectional side views illustrating the sequence of insertion of a particular embodiment of a catheter of the present invention into a tubal insertion catheter, showing the extension of the folded sleeve and the inflation of the distal balloon. [Figure 2D] 1A-1C are schematic cross-sectional side views illustrating the sequence of insertion of a particular embodiment of a catheter of the present invention into a tubal insertion catheter, where irrigation is performed to remove cells from the fallopian tube lumen wall. [Figure 3] FIG. 1 is a schematic diagram of a prior art hysteroscope suitable for deploying embodiments of the inventive catheters disclosed herein. [Figure 4] 1 is a schematic diagram of an embodiment of a proximal introducer catheter. [Figure 5A] 1 is a schematic cross-sectional view of a folded sleeve having an elastic distal balloon tip in a deflated state. [Figure 5B] 1 is a schematic cross-sectional view of a folded sleeve having an elastic distal balloon tip in an inflated state. [Figure 6A] 1 is a schematic cross-sectional view of a folded balloon having an outer configuration sleeve in a deflated state. [Figure 6B] 1 is a schematic cross-sectional view of a folded balloon having an outer configuration sleeve in an inflated state. [Figure 6C] 10A-10C are a series of views of an embodiment of a folded balloon having an outer configuration sleeve. [Figure 7A] FIG. 1 is a schematic cross-sectional view of a turn-up (sleeve and elastic balloon) with a non-elastic delivery balloon in a deflated state. [Figure 7B] FIG. 1 is a schematic cross-sectional view of a turn-up (sleeve and elastic balloon) with a non-elastic delivery balloon in an inflated state. [Figure 7C] 10A-10C are a series of views of an embodiment of a turn-up (sleeve and elastic balloon) with a non-compliant delivery balloon. [Figure 8A] FIG. 1 is a schematic cross-sectional view of a turn-up (sleeve and elastic balloon) with a perfusion lumen in a deflated state. [Figure 8B] FIG. 1 is a schematic cross-sectional view of a turn-up (sleeve and elastic balloon) with a perfusion lumen in an inflated state. [Figure 9A] 1 is a schematic cross-sectional view of a folded balloon catheter configured to be placed within an insertion catheter in a deflated state with the filament spiral distal to the insertion point. FIG. [Figure 9B]1 is a schematic cross-sectional view of a folded balloon catheter configured to be placed within an insertion catheter in an inflated state with the filament spiral distal to the insertion point. FIG. [Figure 9C] FIG. 1 is a diagram of an exemplary spiral filament having a diameter of 15 millimeters (mm). [Figure 9D] 1 is a schematic cross-sectional view of a folded balloon catheter configured to be placed within an insertion catheter in a deflated state, with the filament spiral heat sealed to the balloon and distal to the insertion point. FIG. [Figure 9E] FIG. 1 is a schematic cross-sectional view of a folded balloon catheter configured to be placed within an insertion catheter in an inflated state, with the filament spiral heat sealed to the balloon and distal to the insertion point. [Figure 10] FIG. 10 is a side view of a prior art hysteroscope for deploying the catheter of FIGS. 9A-9E. [Figure 11A] 1 is a schematic cross-sectional view of a folded balloon catheter in a deflated state, the folded balloon catheter having an inflation brush distal to the insertion point and configured to be placed within an insertion catheter. FIG. [Figure 11B] 1 is a schematic cross-sectional view of a folded balloon catheter in an inflated state, the folded balloon catheter having an inflation brush distal to an insertion point and configured to be disposed within an insertion catheter. FIG. [Figure 12A] 1 is a schematic cross-sectional view of a deflated folded balloon catheter configured to be placed within an insertion catheter, with the expanded foam distal to the insertion point. FIG. [Figure 12B] 1 is a schematic cross-sectional view of a folded balloon catheter in an inflated state, the folded balloon catheter having an expanded foam distal to an insertion point and configured to be disposed within an insertion catheter. FIG. [Figure 13A] 1 is a schematic cross-sectional view of a folded balloon catheter in a deflated state, having an enlarged inflated spherical balloon appendage distal to the insertion point, configured to be placed within an insertion catheter. [Figure 13B]1 is a schematic cross-sectional view of a folded balloon catheter in an inflated state, having an enlarged inflatable spherical balloon appendage distal to the insertion point and configured to be placed within an insertion catheter. FIG. [Figure 14A] 1 is a schematic cross-sectional view of a folded balloon catheter in a deflated state, with the superelastic coil distal to the insertion point, configured to be disposed within an insertion catheter. FIG. [Figure 14B] 1 is a schematic cross-sectional view of a folded balloon catheter in an inflated state, the folded balloon catheter having a superelastic coil distal to an insertion point and configured to be disposed within an insertion catheter. FIG. [Figure 15A] FIG. 1 is a schematic cross-sectional view of a folded balloon catheter in a deflated state, having an enlarged inflation spiral balloon appendage distal to the insertion point, configured to be placed within an insertion catheter. [Figure 15B] FIG. 1 is a schematic cross-sectional view of a folded balloon catheter in an inflated state, having an enlarged inflation spiral balloon appendage distal to the insertion point and configured to be placed within an insertion catheter. [Figure 16A] 1 is a schematic cross-sectional view of a folded arc balloon cannula in a deflated state distal to an insertion point, configured to be placed within an insertion catheter. FIG. [Figure 16B] 1 is a schematic cross-sectional view of a folded arc balloon cannula configured to be placed within an insertion catheter and in an inflated state distal to an insertion point. FIG. [Figure 17A] 1 is a schematic cross-sectional view of a folded balloon cannula in a deflated state having a lumen pressurized to unfold the fold and configured to be placed within an insertion catheter. FIG. [Figure 17B] 1 is a schematic cross-sectional view of a folding balloon cannula in an inflated state having a lumen pressurized to unfold the fold and configured to be placed within an insertion catheter. FIG. [Figure 18]FIG. 10 is a diagram of a platinum coil wire having fibers and operable in connection with a catheter such as those shown in FIGS. 9A-9E herein. [Figure 19] FIG. 11 is a diagram of a separate dilation portion with a lumen of the catheter of FIG. 10. [Figure 20] FIG. 11 is a view of a separate extension portion of the catheter of FIG. 10 in a deployed configuration beyond the orifice. [Figure 21A] FIG. 1 is a schematic cross-sectional side view of a ball-tip folded balloon catheter according to an embodiment of the present invention prior to deployment of the balloon from within the hollow spring. [Figure 21B] FIG. 1 is a schematic cross-sectional view showing a ball-tip folded balloon catheter according to an embodiment of the present invention, in which the balloon is folded through a hollow spring. [Figure 22A] FIG. 10 is a diagram of a folded balloon according to an embodiment of the present invention emerging from a nylon flexible tip with a spherical ball. [Figure 22B] FIG. 10 is a diagram of a folded balloon according to an embodiment of the present invention emerging from a nylon flexible tip with a spherical ball. [Figure 22C] FIG. 10 is a diagram of a folded balloon according to an embodiment of the present invention emerging from a nylon flexible tip with a spherical ball. [Figure 23A] FIG. 1 is a schematic cross-sectional side view illustrating a sheathed folded balloon tip catheter in accordance with an embodiment of the present invention. [Figure 23B] FIG. 23B is a diagram of the sheathed folded balloon tip catheter of FIG. 23A in accordance with an embodiment of the present invention. [Figure 23C] 23B is a diagram of the sheathed folded balloon tip catheter of FIG. 23A with a high pressure tubing reservoir and inflation device according to an embodiment of the present invention. [Figure 24] FIG. 1 is a schematic cross-sectional side view of a sheathed, folded balloon-tip catheter constructed with a superelastic pushrod and helical carrier in accordance with an embodiment of the present invention. [Figure 25]FIG. 1 is a side view showing a sheathed, folded balloon tip catheter configured with a handle and drive wheel for advancing and retracting the balloon in accordance with an embodiment of the present invention. [Figure 26A] FIG. 26 is a schematic cross-sectional view of the handle portion of FIG. 25. [Figure 26B] FIG. 26B is a detailed view of the gear system of the handle portion shown in FIG. 26A. [Figure 27] FIG. 1 is a schematic cross-sectional side view illustrating a folded balloon tip catheter according to an embodiment of the present invention with a thin-walled tube having a diameter smaller than the inflated diameter of the folded balloon for insertion into the uterotubal junction of a patient. [Figure 28] FIG. 1 is a schematic cross-sectional side view showing a folded balloon tip catheter according to an embodiment of the present invention, with one or more flexible plastic monofilament strands attached to the distal end of a cannula that extends into the folded balloon tip for insertion into the uterotubal junction of a patient. [Figure 29A] FIG. 1 is a side perspective view of a balloon tip according to an embodiment of the present invention that is steerable using a guidewire. [Figure 29B] FIG. 1 is a side perspective view of a balloon tip according to an embodiment of the present invention that is steerable using a guidewire. [Figure 29C] FIG. 1 is a side perspective view of a balloon tip according to an embodiment of the present invention that is steerable using a guidewire. [Figure 30] FIG. 1 is a side perspective view of a balloon catheter having a smaller diameter lead balloon tip in accordance with an embodiment of the present invention. [Figure 31] FIG. 1 is a side perspective view of a balloon catheter having a flexible guidewire on its distal end in accordance with an embodiment of the present invention. [Figure 32] FIG. 13 is a partial side perspective view of a balloon catheter prior to folding back the striped balloon into the catheter or cannula of FIG. 12 in accordance with an embodiment of the present invention. [Figure 33] FIG. 1 is a schematic cross-sectional side view illustrating a sheathed folded balloon tip catheter in accordance with an embodiment of the present invention. [Figure 34] FIG. 1 is a side perspective view of a thread having a series of knots or stitches according to an embodiment of the present invention. [Figure 35] 10A-10C illustrate several steps for unfolding a balloon used in an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention is useful for engaging the inner walls of the fallopian tubes and efficiently removing cells therefrom for diagnostic purposes, and in some embodiments, devices and processes are provided for the collection of such cells in a minimally invasive procedure performed without skin incision.

[0012] Where a range of values ​​is given, it is understood that each intervening value between the upper and lower limits of that range, to the nearest tenth of the lower limit, is also specifically disclosed, unless the context clearly dictates otherwise. Each smaller range between any stated or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. 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 range is also encompassed within the invention. When a stated range includes one or both of the limits, ranges excluding either or both of those included limits are also encompassed within the invention.

[0013] It should be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to a "balloon" includes a plurality of such balloons, a reference to a "channel" includes a reference to one or more channels and equivalents thereof known to those skilled in the art, and so forth.

[0014] An embodiment of an inventive catheter for fallopian tube diagnosis is provided for performing a minimally invasive procedure that includes (1) accessing the proximal opening of the fallopian tube via an intrauterine approach, (2) advancing an introducer catheter to insert a cannula and form a fluid-tight seal with the proximal opening, (3) using a second catheter inside the introducer catheter to advance it down the length of the fallopian tube and out into the abdominal cavity, (4) retracting the second catheter and inflating a balloon on the end of the second catheter until the balloon seals the distal opening of the fallopian tube (retraction of the second catheter creates contact with the inner luminal surface of the fallopian tube, separating cells for improved sampling), and (5) providing for irrigating the fallopian tube and collecting irrigation fluid for cytology or cytological analysis.

[0015] Additionally, certain embodiments of the catheters of the present invention for fallopian tube diagnosis are provided for performing a minimally invasive procedure, including (1) accessing the proximal opening of the fallopian tube via an intrauterine approach, (2) advancing an introducer catheter to cannulate the proximal opening, (3) using a second catheter inside the introducer catheter to advance inside the fallopian tube (an inflated balloon on the end of the second catheter is advanced across the proximal portion of the fallopian tube and further inverted into the fallopian tube), (4) the balloon contacts the endoluminal surface of the fallopian tube to scrape cells for improved sampling, and (5) the balloon is removed and inserted into a vial for cell collection, which is then processed.

[0016] Embodiments of the catheter of the present invention are configured for insertion into the fallopian tubes, which is typically very difficult. The fallopian tubes are curved, and the soft tissue of the tubes collapses, leading to multiple constrictions when attempted passage. This is particularly true of the uterotubal junction (UTJ), which is prone to penetration when a medical device is inserted into the deflated state that occurs within the uterus approximately 1 cm distal to the proximal opening (opening) of the fallopian tube. Additionally, the UTJ typically exhibits a downward bend, with the lumen size at constriction being as large as 0.3 mm or 0.5 mm, while the lumen size of the fallopian tubes adjacent to the UTJ is approximately 1 mm.

[0017] In at least one embodiment of the present invention, an elongated, folded balloon within the catheter lumen is initially deployed. Upon pressurization within the catheter, the balloon unfolds, and the unfolding mechanism creates a passage through the fallopian tube, regardless of tubal kinking or contraction. The majority of the balloon's length is substantially inelastic, so that the balloon does not substantially expand or dilate the fallopian tube when it unfolds, and preferably, the fallopian tube does not expand or dilate when the balloon unfolds. Inflating the balloon may rupture or injure the fallopian tube. However, the design incorporates an elastic distal balloon end that allows the distal opening to seal when the inflated balloon is retracted.

[0018] The process of the present invention, common to various embodiments of the device, involves deployment of the distal end of a catheter. In some embodiments of the present invention, the distal end of the inventive catheter is delivered to the proximal end of the fallopian tube using a conventional hysteroscope. Regardless of the deployment mode, the retracted portion of the inventive catheter extends into contact with the inner wall of the fallopian tube. Surprisingly, it has been found that the act of extending the portion scrapes enough cells from the fallopian tube wall to allow for histological evaluation. This is apparent in the flat surface of the apparently non-abrasive characteristic. In some embodiments, abrasion is present on the contact surface of the tube, but such abrasion is not believed to be inevitable. It has also been surprisingly found that retraction of the extension portion still removes many cells. In other processes of the present invention, the extension portion is retracted before removal of the catheter to prevent the scraped fallopian tube cells from dispersing into the surrounding tissue. Contacting the exposed, now cell-covered portion with a microscope slide or other diagnostic substrate is sufficient to test for abnormal cells, particularly cancer cells.

[0019] Referring now to the figures, in Figures 2A-2D, an introducer catheter 10 has a folded inelastic sleeve 12 and a distal elastic balloon 14 attached thereto, and the elastic balloon 14 is inserted through the introducer catheter 10 within the working channel 22 of a surgical hysteroscope 20 (Figure 3) and used to cannulate the proximal opening of the fallopian tube 1 (Figure 2A), inflating the elastic balloon 14 and unfolding the sleeve 12 along the length of the fallopian tube 1, inflating the distal elastic balloon 14 (Figure 2B), and slightly retracting the folded elastic sleeve 12 so that when it is fully advanced, the inflation of the elastic balloon 14 seals the distal opening 18 of the fallopian tube 1 (Figure 2C). FIG. 2D shows the introduction of saline to irrigate the length of the fallopian tube 1 between the introducer catheter 10 and the folded back sleeve 12, retracting the inflated elastic balloon 14 to seal the distal opening, followed by collection of the irrigation fluid and obtaining cell samples from substantially the entire length of the fallopian tube 1 for cell analysis in the detection of ovarian cancer or other pathologies.

[0020] The catheter 10, as described above and in more detail below, may be introduced into a patient's uterus using a surgical hysteroscope 20, an example of which is shown in FIG. 3. The surgical hysteroscope 20 includes an endoscope and multiple channels, one channel for irrigating and distending the uterus and allowing endoscopic visualization, and one or more additional channels 22 for advancing instruments and / or catheters distal to the hysteroscope. A proximal introducer catheter 10 (see FIGS. 2A and 4) can be advanced through the working channel of the surgical hysteroscope and used to cannulate the proximal openings of the fallopian tubes. A balloon 14 on the proximal introducer catheter 10 is inflated to occlude the proximal openings, and a folding balloon catheter is advanced through the proximal introducer catheter 10 into the proximal portion of the fallopian tube. The sleeve / balloon element 14 is fully folded back, and the inflated balloon tip is retracted to seal the distal opening. Irrigation can be introduced through port 11 and aspirated through irrigation port 11 of the proximal introducer catheter 10 to collect samples. Irrigation can also be introduced through both the folded balloon catheter and the proximal introducer catheter and then aspirated through one or both ports (11, 13).

[0021] In the present embodiment of the catheter, the sleeve 12 of the folded sleeve catheter is preferably a flexible, elongated, substantially inelastic tube, with an elastic balloon tip 14 attached to the distal end of the sleeve 12, as seen in FIGS. 5A and 5B. The inelastic tube 12 may have a plurality of ridges 15 along its length, as shown in FIG. 5B, which are on the outer surface of the tube 12 when the tube 12 is extended / deployed. Before deployment, the tube 12 is folded back, so that the ridges 15 are on the inner surface, as shown in FIG. 5A. When the sleeve 12 is fully unfolded, as in FIG. 5B, the ridges 15 are on the outer surface, and are exposed to the luminal surface of the fallopian tube. These ridges 15 enhance the sleeve's ability to collect cells when the balloon is retracted. Alternatively, the outer surface of the unfolded inelastic tube may be covered with a cloth or other fabric to enhance cell separation during balloon retraction.

[0022] 6A-6C show an embodiment of a folded sleeve catheter 10A that provides greater protection than the folded sleeve catheter embodiment of FIGS. 5A and 5B due to the bond between the balloon and sleeve of the folded sleeve catheter 10A during deployment. The configuration of the embodiment of FIGS. 6A-6C involves attachment of an elongated elastomeric balloon to the distal tip of the folded sleeve catheter. A substantially inelastic sleeve 17, slightly shorter than the elastomeric balloon 14, is attached to the elastomeric balloon 14 at the distal tip of the catheter and folded back to lie inside the elastomeric balloon. When the balloon / sleeve combination 14A is unfolded, the inelastic sleeve 17 emerges from the double wall 19 of the catheter 10A and lies on the exterior surface of the elastomeric balloon, confining it over most of its length and preventing it from potentially rupturing the fallopian tube during advancement of the folded sleeve through the fallopian tube. When the balloon / sleeve is fully unfolded, the distal elastic balloon inflates to 3-5 times the diameter of the sleeve, blocking the distal opening when the catheter is retracted, accompanied by retraction of the inflated balloon. If desired, the catheter may include a port 11 to allow irrigation between the balloon and outer sleeve to occur.

[0023] 7A-7C show an embodiment of a folded sleeve catheter 10B, in which a concentric, double-walled catheter is provided with three folds attached to the distal catheter tip: (1) an elongated, inelastic balloon 21 is attached to the distal tip of an inner catheter 23, the balloon 21 residing within the lumen 25 of the inner catheter; (2) an elongated, elastic balloon 14B is attached to the distal tip of the outer wall 27 of the catheter 10B, the elastic balloon 14B being equal in length to and inside the inelastic balloon 21; and (3) an inelastic sleeve 29 is attached to the distal tip of the outer catheter wall 27, the inelastic sleeve 29 being shorter than the elastic balloon 14B and inside the elastic balloon 14B. Pressurization of the inner catheter 23 unfolds the inelastic balloon 21, expelling the elastic balloon 14B and the outer confinement sleeve 29. Once all three layers are fully unfolded, the elastic balloon 14B is inflated by pressurization between the walls of the inner and outer catheters. The inelastic sleeve 29 confines the elastic balloon 14B over most of its length, and the distal, unconfined tip of the balloon 14T expands to form an occlusion element. A potential advantage of this design is reduced friction during the unfolding process. In this embodiment, the inelastic balloon 21 delivers the elastic balloon and confining sleeve. The elastic balloon does not inflate until it is fully unfolded, and therefore does not increase friction with the walls of the unfolding sleeve during unfolding as in previous embodiments, which has significant advantages for ease of deployment, especially when working with small diameter catheters required to penetrate the fallopian tubes.

[0024] 8A and 8B show an embodiment of a folded sleeve catheter 10C in which an inelastic sheath 29A has a small lumen 31 for irrigation, which is connected to a third port 11A, which is used for fluid irrigation and also for aspiration to obtain cytology samples.

[0025] 9A-9E show a modified design. An elongated balloon 32, with an expandable member 34 attached to its distal end, is folded back into the lumen 36 of the catheter 30. When folded back, the expandable member 34 resides inside the elongated balloon 32. In some embodiments of the present invention, the expandable member 34 is a helix comprised of multiple loops 38 of filament. The filament forming the expandable member 34 is readily formed from a variety of materials, including, for example, monofilament plastic materials such as nylon or polypropylene, fluoropolymers, or polylactic acid; metals such as stainless steel, titanium, or platinum; and superelastic metals such as nitinol. In some embodiments, fiducial markers are present (not shown) to facilitate subsequent return to the location for cell sampling. It should also be recognized that the inflation portion may have variations in configuration. For example, the expansion portion 34 may include a plurality of outwardly directed plastic or metal bristles 40 (FIG. 18); the expansion portion 34 may exist as an elongated strand of material that, upon release from its confinement inside the catheter, assumes a curled configuration 38, a fanned configuration 42, or a balled configuration 44 to a predetermined shape (FIGS. 11A-11B or 14A-14B); or the expansion portion 34 may be a compressed plastic foam that expands upon release into a moist environment (FIGS. 12A-12B). When the catheter adjacent the distal opening is pressurized, the balloon 32 unfolds, forcing the folded portions outward to an extended position and into contact with the fallopian tube lining cells. In some embodiments of the present invention, when the balloon is fully unfolded, the expansion portion 34 is delivered from the distal opening of the fallopian tube into the abdominal cavity. In some embodiments, the expansion portion 34 has an outer diameter of approximately 15-20 mm.

[0026] An advantage of an extension portion 34 having multiple bristles is that it provides a larger surface area from which cells can be collected, including an area that may not be exposed to shear forces when the device is retracted. This approach can maximize cell collection and minimize the amount of cells swabbed as the device is pulled through the fallopian tube or retracted into a sheath, as shown in Figures 18-20. In those embodiments in which the extension portion has a relatively large surface area, cell collection per linear unit of fallopian tube is typically increased under conditions such as pressurization, compared to an extension portion without a contour.

[0027] In still other embodiments of the catheter of the present invention, the expansion portion may have the following configurations when deployed, such as a plurality of filaments attached to the distal end of the balloon 32 that splay outward when the balloon is folded back to form a brush 42 (FIGS. 11A-11B); a plastic foam structure 46 that is compressed inside the balloon 32 and expands when the balloon 32 is folded back and exposed to a fluid environment (FIGS. 12A-12B); an inelastic sleeve 46 attached to the distal end of the balloon 32 (FIGS. 11A-11B); Examples include elastic or inelastic balloons 48 at the end (FIGS. 13A-13B), folded balloons with superelastic wire coils (FIGS. 14A-14B), helically folded balloons 50 (FIGS. 15A-15B), folded distal arc balloons 52 (FIGS. 16A-16B); or elastic elongated filaments of plastic or metal that assemble into a three-dimensional structure when the balloon is folded, such as an inflation portion 34 with a lumen 54 (FIGS. 17A-17B) and multiple outwardly directed bristles (FIG. 18). It should be appreciated that any of these embodiments of the catheter extensions of the present invention are readily compatible with fiducial markers used to navigate back into the fallopian tubes, when necessary. Such markers are known in the art and include, for example, radiopaque markers, isotopic markers, and radiofrequency markers. In yet other embodiments, the biodegradable or permanent extension is detached from the catheter. In yet other embodiments, the dilator delivers a therapeutic agent to the fallopian tube tissue, such as a chemotherapeutic agent, an antibiotic, an anti-inflammatory agent, or a combination thereof.

[0028] As the catheter is retracted into the working channel of the hysteroscope, cells are separated from the entire length of the inner surface of the fallopian tube. In some embodiments, the extension is folded back by reducing gas pressure with a balloon to protect the collected cells in the inner bore of the catheter tip region (FIG. 19).

[0029] While not intending to be bound by any particular theory, even in some examples of uncontoured expansion segments, the expansion segment generates enough friction between the outer surface of the expansion segment and the inner lining of the fallopian tube to separate and attach cells to the expansion segment. The inflated spiral at the distal end of the balloon contacts the fimbria at the distal end of the fallopian tube and collects the cell sample as the spiral is retracted. Because the inner diameter of the fallopian tube increases from the proximal to the distal end, the expansion segment ensures that the cell sample is obtained at the distal end of the fallopian tube (the fimbria portion of the fallopian tube). In some procedural embodiments, the elongated balloon and distal expansion segment are retracted into the working channel of the hysteroscope to avoid losing the cell sample when the hysteroscope is removed from the patient. An elastomeric seal at the proximal end of the working channel of the hysteroscope seals against the outer surface of the catheter. Markings on the catheter body indicate the retraction length required to ensure that the elongated balloon and distal spiral reside within the working channel of the hysteroscope. When the hysteroscope is removed from the patient, in some embodiments, a syringe containing saline solution is attached to the luer fitting at the proximal end of the working channel, and the saline is used to flush the cells collected by the elongated balloon and inflation spiral into a test tube. It should be appreciated that the cells attached to the extension are easily collected for testing by conventional techniques and prepared for cytological, molecular, or genetic testing.

[0030] In an alternative embodiment of the catheter shown in FIGS. 17A-17B, in which a coil is attached to the end of the folded balloon, a lumen is provided formed from the exemplary material polyethylene terephthalate (PET). The folding process follows that of the previous embodiment. This alternative embodiment includes an inflation side port and a proximal seal, which allows the balloon to fold while maintaining an orifice through the lumen to allow fluid communication between the hysteroscope and the patient's body tissue. When folded, the lumen forms a passageway for a separate dilator or surgical instrument package. An example of such a collection device is the helical shape shown in FIGS. 19 and 20. It should be appreciated that to prevent distal cells from being wiped off by the proximal inner surface of the fallopian tube upon removal of the device, cells may be collected from a specific portion of the fallopian tube, such as the fimbria, and then pulled back into the lumen.

[0031] 21A and 21B are schematic cross-sectional side views of a ball-tip folded balloon catheter in accordance with at least one embodiment of the present invention. A spherical ball 122 is attached to the distal end of a spring tip 124 that is affixed to a catheter 126 and is configured to negotiate a patient's uterotubal junction (UTJ) without perforating the sidewall of the UTJ. The spring tip 124 and spherical ball 122 have an open lumen 128 extending therethrough. The spherical ball 122 on the spring tip 124 has a diameter of approximately 0.8-1.0 mm, and the hollow spring tip 124 has a length of approximately 1.5 cm and an outer diameter of approximately 0.6 mm. The hollow spring tip 124 may be a metal (stainless steel or superelastic metal, e.g., Nitinol) coil spring with a sheath of thin-walled plastic heat-shrink tubing made of nylon, PET (polyethylene terephthalate), or similar material over its outer surface. In certain embodiments of the present invention, the spring tip 124 may be a metal coil spring co-extruded into a tubular plastic body. Alternatively, the hollow spring tip 124 may be a flexible plastic tube made of nylon, polyethylene terephthalate (PET), polyether block amide (PEBAX®), or similar material. The long, folded balloon 130 is located inside the hollow spring tip 124. The everting balloon 130 extends proximally inside a main lumen 132 of an introducer catheter 126 (a generally flexible tubular structure) or cannula (a generally synthetic tubular structure), with the proximal end of the everting balloon 130 attached to a push rod 134 that penetrates a seal 136 at the proximal end of the catheter 126 or cannula. When used in surgery on a patient, the flexible ball tip 122 is manually advanced through the uterotubal junction. Once the flexible ball tip 122 and spring tip 124 have successfully passed through the uterotubal junction, the push rod 134 is advanced to pierce the seal 136 of the pre-pressurized introducer catheter 126 or cannula. Advancement of the push rod 134 controls the unfolding of the balloon 130 out of the hollow spring tip 124 and down the length of the fallopian tube.

[0032] In an embodiment of the present invention, when an elongated balloon that is initially folded within the catheter lumen is deployed, the balloon folds under pressure inside the catheter, and the unwinding mechanism of the fold follows the fallopian tube regardless of kinking or contraction of the fallopian tube. A majority of the length of the balloon should be substantially inelastic so that when the balloon folds, it does not substantially inflate or deflate the fallopian tube, and the fallopian tube does not expand or dilate when the balloon unfolds. Inflation of the balloon may rupture or injure the fallopian tube.

[0033] The method of the present invention, common to various embodiments of the device, involves deploying the distal end of a catheter. In some embodiments of the present invention, the distal end of the catheter of the present invention is delivered to the proximal end of the fallopian tube using a conventional hysteroscope. Regardless of the deployment mode, the retracting portion of the catheter of the present invention is extended to contact the inner wall of the fallopian tube. Surprisingly, it has been found that the act of extending the retracting portion scrapes enough cells from the fallopian tube wall to allow for histological evaluation. This has been observed for characteristic flat surfaces that appear unscraped. In some embodiments, scraping is present on the contact surface of the tube, but such scraping is not believed to be inevitable. It has also been surprisingly found that retracting the extending portion still detaches many cells. In other processes of the present invention, the extending portion is retracted before removing the catheter to prevent the detached fallopian tube cells from dispersing into the surrounding tissue. Contacting the exposed, now cell-covered portion with a microscope slide or other diagnostic substrate is sufficient to test for abnormal cells, particularly cancer cells.

[0034] A catheter 126, as described above and in more detail below, is introduced into the patient's uterus using a surgical hysteroscope 40, an example of which is shown in FIG. 3. The surgical hysteroscope includes an endoscope and multiple channels, preferably one channel for irrigating and distending the uterus and allowing endoscopic visualization, and one or more additional channels for advancing instruments and / or catheters distal to the hysteroscope. A catheter 126 (see FIGS. 21A and 21B) is advanced through the working channel of the surgical hysteroscope, and the catheter 126 is used to cannulate the proximal openings of the fallopian tubes. A folded balloon 130 is advanced through the proximal catheter 126 into the proximal portion of the fallopian tube.

[0035] 22A-22C are a series of illustrations of a folded balloon 130 emerging from a nylon flexible tip 152 with a spherical ball 122 in accordance with an embodiment of the present invention. The nylon flexible tip 152 and spherical ball 122 are configured to pass through the patient's uterotubal junction (UTJ) for deployment of the folded balloon 130 within the fallopian tube. In some embodiments of the nylon ball tip, the folded balloon catheter 150 is configured with a 0.9 mm ball tip on a nylon tip with a diameter of 0.66 mm and a length of 18 mm, i.e., a tip (24 atm; 2.4 x 10 6 The catheter is a 4 Fr (1.27 mm) with a 0.64 mm diameter manual balloon that loops back through and beyond the septum (Pa).

[0036] FIG. 23A is a schematic cross-sectional view of a sheathed, folded-back balloon-tip catheter 160 or cannula according to an embodiment of the present invention, as shown in the diagram of FIG. 23B. A long, folded-back balloon 130, having an outer diameter of about 0.8-1.0 mm, is folded back over the distal end of the catheter 126 or cannula for a length of about 1-3 cm, most preferably 1.2-1.5 cm. The balloon 130 is pressurized to about 14-24 atm (206-353 psi; 1.4×10 6 ~2.4×10 6The balloon 130 is inflated with fluid to a pressure of 1.5 Pa. The pressurized balloon 130 has rounded ends, some flexibility along its length, and sufficient longitudinal strength to allow it to be manually advanced through the uterotubal junction. In certain embodiments, the balloon 130 is constructed of a thin-walled plastic material such as polyethylene terephthalate (PET), polyethylene, nylon, or similar materials, and the balloon 130 has a wall thickness of approximately 0.25 mil (0.00025"; 0.00635 mm). The balloon may be opaque in color to facilitate visualization during use. The fully unfolded length of the balloon 130 is approximately 7 cm, and when fully unfolded, the balloon 130 extends into the patient's fallopian tube after successful advancement of the 1.5 cm length of the folded balloon through the uterotubal junction. The folds of the balloon 130 are attached to the proximal end of the catheter 126. The insertion of the balloon 130 is accomplished in a controlled manner by advancing the push rod 134 to penetrate a fluid-tight seal 136 at the catheter 126. At least a portion 167 of the catheter 126 is preferably transparent so that the movement of the balloon 130 can be viewed through a hysteroscope through which the catheter is inserted, allowing the user direct observation of the insertion procedure. The catheter 126 may be constructed of a polymer such as nylon (preferred), Pebax®, polyurethane PET (polyethylene terephthalate), polyethylene, or polyvinyl chloride (PVC) plastic, with or without a polymer or metal coil or braid reinforcement.

[0037] However, a 1.5 cm long balloon of the above dimensions may not remain straight when folded out of the catheter 126 or cannula. Rather, the balloon 130 may assume a curved configuration, either a single C-curve or an S-curve. However, inserting a cannula with a curved balloon into the proximal opening of the fallopian tube and advancing it past the uterotubal junction can be difficult or nearly impossible. The 1.5 cm length of the folded balloon 130 can be straightened using an outer plastic sheath 162, which is coaxial with the catheter 126 or cannula and covers the 1.5 cm tip of the folded balloon. At least a portion 167 of the sheath 162 is preferably transparent, allowing the movement of the balloon 130 to be viewed through a hysteroscope through which the catheter is inserted, allowing the user to directly observe the insertion procedure. The sheath 162 may be constructed of a polymer such as nylon (preferred), Pebax®, polyurethane PET (polyethylene terephthalate), polyethylene, or polyvinyl chloride (PVC) plastic, with or without polymer or metal coil or braid reinforcement.

[0038] FIG. 35 illustrates the linear unfolding of the balloon during deployment. In the cross-section of the folded balloon, one end of the balloon at point X is fixed, while the other end at point Y is movable. The balloon is folded from the position shown in step 1 to the position shown in step 2 to the position shown in step 3. During the unfolding process, points A, B, and C move toward the left of the figure. As shown, point A moves from the inner diameter to the outer diameter of the balloon as the balloon unwinds toward the left of the figure. In practice, the balloon folded during the preparation step is advanced into the proximal end of the fallopian tube. Further folding (stretching) of the balloon (to a total of 2-3 cm into the fallopian tube) is achieved by further rotation of the drive wheel 204. The balloon 130 is then deflated by releasing the pressure in the inflation device. The balloon 130 is then retracted from the fallopian tube. Because the fallopian tube is a potential space, the tubal tissue collapses around the balloon. As the balloon fills the fallopian tube, the surface area of ​​the balloon is equal to the surface area of ​​the inside of the fallopian tube. This matched surface area allows for optimal collection of tissue from the inner surface of the fallopian tube.

[0039] To further optimize tissue collection, wrinkles may be added to the surface of the balloon, which wrinkles as the balloon deflates, forming multiple edges that also aid in cell collection. These edges function in a manner similar to the edges of the curettes on the approved U-scope device and the jaw edges on the approved biopsy forceps device. Similar to these features of the approved device, the edges formed by the wrinkled loons concentrate the contact force on the anatomical wall for cell collection. However, because the collection surface is a polymer balloon, contact with endothelial cells is more atraumatic than the stainless steel contact surface of prior art diagnostic devices. The atraumatic nature of the wrinkles on the balloon for collecting cellular tissue allows repeated inflation / deflation of the balloon inside the fallopian tube, allowing cells to be freely scraped away. The balloon deployment device of the present invention is then removed from the working channel of the hysteroscope and from the patient. Once the device is removed from the patient, cells can be removed from the balloon by immersing the balloon in a cell preservative and agitating it to agitate the cells. Alternatively, both the balloon and sheath may be separated and placed in a cytological preservative. In certain embodiments, when the balloon is deflated and removed, the sheath may extend and unfold over the balloon to protect the tissue sample present on the balloon surface.

[0040] FIG. 24 is a schematic cross-sectional view of a sheathed, folded balloon-tip catheter 160′ according to an embodiment of the present invention. The folded balloon-tip catheter 160′ is configured with a superelastic pushrod 175 and a helical carrier 176, eliminating the need for a pushrod to extend backward relative to its overall length. The pushrod 175 is constructed of a superelastic material, such as nitinol (nickel-titanium compound) wire. In this case, the length of the pushrod 175 may be wound multiple times within a tubular helical carrier 176 made of polyethylene or polytetrafluoroethylene (Teflon®). The helical outer diameter of the helical carrier 176 may be approximately 8 cm, providing an even smaller proximal working length. The plastic helical carrier 176 may be attached to the proximal Tuohy-Borst fitting 136 on the catheter using a flexible strap 177 constructed of a plastic or silicone rubber material. In certain embodiments, the superelastic push rod 175 has a diameter of approximately 0.025" (0.635 mm), making it difficult to grasp this wire and push it forward through the Tuohy-Borst seal 136. Therefore, a flexible grip 178 is added that slides freely over the push rod 175 and provides a good grip for advancement of the push rod 175 when compressed between the thumb and index finger. The flexible grip 178 may be an oval cross-sectional frame made of polyvinyl chloride, silicone rubber, or a similar flexible compound, with internal dimensions of approximately 2 cm in length, 1 cm in width, and 3 mm in height, and a wall thickness of approximately 2 mm. Holes in the proximal and distal faces of the grip are slip-fit ​​to fit the push rod 175.

[0041] 25 is a schematic side view of an embodiment of the present invention of a sheathed, fold-back balloon-tip catheter 200 configured with a handle 202. The handle 202 has a drive wheel 204 that advances and retracts a push wire 206 that straightens out the folds of the balloon 130 (gradually extending the inside out). The drive wheel 204 may be made of plastic, such as ABS. The outer edge of the drive wheel 204 may have a notch to facilitate gripping the drive wheel 204 during operation of the catheter 200. The top surface of the drive wheel 204 may have a molded arrow indicating the correct direction to rotate to unfold the balloon. The opposite side of the drive wheel 204 may have a square boss that inserts into a drive gear.

[0042] The catheter 200 holds the balloon 130 within a shaft 210 (which may be made from stainless steel and nylon tubing), a sheath 212, and a sheath knob 214. The handle 202 also has an extension tube 216 attached to a luer fitting 218 on the handle body. To enable balloon advancement, the balloon 130 and shaft 210 are pressurized with an inflation device (e.g., inflation device 172 in FIG. 23C) attached to the extension tube 216. Once the catheter device 200 is pressurized, the user advances the push wire 206 by rotating the drive wheel 204.

[0043] Figure 26A is a cross-sectional view of the handle portion of Figure 25, and Figure 26B is a detailed view showing the internal handle gear mechanism 220. The drive wheel 204 has a square boss (not shown) that is inserted into a square hole 222 in the drive gear 224. When the drive wheel 204 is rotated clockwise, the square boss rotates the drive gear 224. The drive gear 224 engages and rotates an idle gear 226 and a first gear 228. Similarly, the idle gear 226 rotates a second gear 230 and thereby a third gear 232. The push wire 206 travels between rubber transmission surfaces on and between each of the four large gears (224, 228, 230, 232) and moves while advancing the balloon 130, as shown in Figure 26B. The balloon 130 is advanced until the proximal end of the push wire 206 passes between the drive gear 224 and the first gear 228. The internal handle gear mechanism 220 allows for precise, accurate, and controlled movement for deployment and retraction of the balloon 130.

[0044] The sequence of steps used to enter and navigate the fallopian tube is illustrated in the embodiment of Figure 23A. When it is desired to cross or pass through the uterotubal junction with a 15 mm long, folded balloon 130, an outer plastic sheath 162 is positioned near the proximal opening of the fallopian tube but not into the proximal opening. The outer plastic sheath 162 supports the 15 mm long, folded balloon 130 until it enters the proximal opening. While a short length of pressurized folded balloon 130 emerging from the supporting outer plastic sheath 162 has sufficient longitudinal strength to be manually advanced through the uterotubal junction, an unsupported 15 mm long, folded balloon 130 does not have sufficient rigidity itself and will bend when attempting to advance it through the proximal opening and uterotubal junction.

[0045] The sheath 162 has an outer diameter of 5 French (1.59 mm), and its proximal end is attached to a male luer lock fitting 164 using a Tuohy-Borst seal 136 connector. A Tuohy-Borst adapter is a medical device used to attach catheters to various other devices, forming a seal between the devices. The Tuohy-Borst seal 136 is tightened to provide a snug fit with the catheter or cannula, holding the sheath 162 in place, thereby covering the tip of the folded balloon. The male luer lock fitting 164 preferably mates with a female luer lock fitting on the working channel of the hysteroscope, if present. When these luer fittings are connected, the tip of the outer sheath protrudes approximately 2-3 cm from the distal end of the hysteroscope. The outer sheath also protects the 1.5 cm long folded balloon tip from damage as the catheter or cannula is advanced through the metal hysteroscope working channel. Stainless steel tubing with an outer diameter of 0.050" (1.27 mm) and a wall thickness of 0.004" (0.0102 mm) is preferred for the inner cannula 126 because it provides sufficient rigidity to prevent kinking of the portion protruding from the proximal end of the hysteroscope working channel.

[0046] FIG. 23C is a diagram of the sheathed, folded balloon-tip catheter 160 of FIG. 23A according to an embodiment of the present invention, including a high-pressure tubing reservoir 168 and an inflation device 172. Pressurization of the balloon 130 using fluid injection may be accomplished using a threaded syringe device, commonly known as a deflation device, as well as the inflation device 172. Rotation of the threaded plunger shaft via a releasable lock increases and maintains pressure within the inflation device 172, and a pressure gauge 174 on the inflation device 172 allows for control of the input pressure. Certain embodiments of the sheathed, folded balloon-tip catheter 160 allow for single-person operation of the device. A length of high-pressure tubing 168 is added between the inflation device 172 and an inflation port 166 on the device. The high-pressure tubing 168 may be constructed of a polymer, such as polyurethane or polyvinyl chloride (PVC), with or without a metal coil or braided reinforcement. The pressure tube 168 has a certain inherent elasticity, while the folded balloon is generally inelastic. Upon full pressurization of the balloon 130, the pressure tube 168 contributes a fluid volume to the system. A small amount of fluid is contained in the folded balloon, and this volume is further subtracted by the volume occupied by the push rod 134 (which moves into the balloon 130 during unfolding). The resulting folded balloon volume is small compared to the larger volume of the pressure tube 168, allowing the balloon 130 to unfold its entire length without a significant pressure drop when the sheathed folded balloon-tip catheter 160 is pressurized. A stopcock valve 170 between the pressure tube 168 and the inflation device 172 can be closed after pressurization, allowing the heavy inflation device 172 to be removed from the test field prior to insertion and unfolding of the balloon 130. A hassle-free, single-operator operation is a result of the design embodiment shown in FIG. 23C.

[0047] As discussed above with respect to Figures 23A-23C, the folded balloon 130 extends distally to the catheter tip an overall distance of approximately 7 cm to pass the entire length of the fallopian tube. The folded balloon 130 assumes a donut shape as it exits the catheter tip, with the folded portion having a double-walled configuration. Thus, to create a 7 cm long folded balloon, the push rod 134 must advance a distance of 14 cm. A push rod of this length initially extends rearward from the proximal end of the catheter 126, directly toward the operator's face, making its use cumbersome. Also, a push rod 314 of this length is susceptible to contamination of the sterile device, as the proximal end of the long push rod may come into contact with the physician's face or surgical mask during use. Therefore, it is desirable to provide a push rod system that does not require its entire length to extend rearward. The sheathed, folded-over balloon-tip catheter 200 configured with the superelastic push rod and carrier design of FIG. 24 and the handle 202 of FIG. 25 acts to retract the push rod, avoiding the need to extend the push rod backwards toward the user.

[0048] FIG. 27 is a schematic cross-sectional side view illustrating an embodiment of a folded balloon tip catheter 180 according to the present invention, including a thin-walled tube 182 having a diameter smaller than the inflated diameter of the folded balloon 130 for insertion into a patient's uterotubal junction. The thin-walled tube 182 straightens a portion of the balloon tip 163. The thin-walled tube 182 may have a wall thickness of approximately 0.0005" to 0.001" (approximately 0.0127 mm to 0.0254 mm) and may extend 1.5 cm distal to the tip of the cannula. The thin-walled tube extension 182 supports the balloon 130 and keeps the balloon tip 163 straight, but because the diameter of the thin-walled tube is smaller than the balloon diameter, it allows the balloon 130 to retain flexibility and compressibility, which are necessary for advancing the balloon 130 through the uterotubal junction. In a specific embodiment, the balloon has an outer diameter of 0.04" (1 mm) and an inner tube with an outer diameter of 0.033" (0.0762 mm), a wall thickness of 0.001" (0.0254 mm), and a length of 1.5 cm to support and straighten the balloon.

[0049] 28 is a schematic cross-sectional side view illustrating a folded balloon tip catheter 190 according to an embodiment of the present invention having one or more flexible plastic monofilament strands 192 attached to the distal end of cannula 126 and extending into folded balloon tip 163, thereby supporting and keeping the tip straight for insertion into the patient's uterotubal junction. In a specific embodiment, the one or more flexible plastic monofilament strands 192 extend 1.5 cm into balloon tip 163. The monofilament may be formed of nylon, polypropylene, or other flexible plastic material. The monofilament strand may have a diameter of approximately 0.006" to 0.012" (approximately 0.1524 mm to 0.3048 mm). In a specific embodiment, the balloon has an outer diameter of 0.033" (0.8 mm) with a 0.008" (0.2 mm) diameter nylon monofilament inside a 1.5 cm long folded balloon tip.

[0050] 29A-29C are a series of side perspective views of a steerable balloon tip 252 for a guidewire-folded balloon catheter 250 in accordance with an embodiment of the present invention. As shown in FIG. 29A, the steerable balloon tip 252 is controlled by a rightward guidewire 254 and a leftward guidewire 256. In FIG. 29B, the rightward guidewire 254 is pulled (as indicated by the arrow) to steer the balloon 202 to the right. Conversely, in FIG. 29C, the leftward guidewire 256 is pulled (as indicated by the arrow) to steer the balloon 202 to the left. It should be noted that in addition to the movement in the XY plane achieved with a pair of guidewires as shown, an additional guidewire may be added to allow movement in the Z plane.

[0051] 30 is a side perspective view of a balloon catheter 260 according to an embodiment of the present invention having a smaller diameter lead balloon tip 262 at the distal end of the folded balloon 130. The smaller diameter lead balloon tip 262 is sized to gradually enlarge an opening at the stricture presented by the patient's uterotubal junction, is flexible, and has blunt edges so as not to perforate the wall of the uterotubal junction.

[0052] 31 is a side perspective view of a balloon catheter 270 according to an embodiment of the present invention having a flexible guidewire 272 at the distal end of balloon 130. The flexible guidewire guides balloon catheter 220 through the patient's uterotubal junction.

[0053] In embodiments of the folded balloon catheter of the present invention, a portion of the folded balloon may be treated with a coating of fluoropolymers, silicones, and similar materials that provide a slippery surface for the lead portion of the balloon catheter embodiment that enters the narrowed portion of the fallopian tube.

[0054] FIG. 32 is a partial side perspective view of a striped balloon 130S according to an embodiment of the present invention, prior to folding the striped balloon 130S into the catheter or cannula of FIG. 32. Markings 131 on the balloon provide visual feedback indicators of the balloon's folding progress. In certain embodiments, the markings 131 may be approximately 1 mm wide and spaced at intervals of approximately 1 cm along the entire length of the balloon 130S. The spacing of strips or other visual marker variations on the balloon may be spaced relatively closely together for finer position feedback or relatively far apart for coarse feedback. Other visual markers of folding length include sinusoidal markings having a known periodic length. It should also be appreciated that the length markings may include multiple segments of different colors of known lengths.

[0055] FIG. 33 is a schematic cross-sectional view of a sheathed, folded balloon-tip catheter 280 according to an embodiment of the present invention having a striped balloon 130C. As shown in FIG. 33, the markings 131 on the striped folded balloon 130S, combined with the transparent distal portion 167 of the cannula or catheter 126, provide visual feedback of the balloon's fold. In a specific embodiment, the markings 131 are pads approximately 1 mm wide, spaced approximately 1 cm apart along the entire length of the balloon, and printed or inscribed with a highly visible, permanent marker. Pad printing (also called tampography) is a printing method capable of transferring two-dimensional images onto three-dimensional objects. Other patterns may be used instead of or in addition to the markings 131 on the surface of the balloon 130S. For example, the markings 131 on the balloon 130S may be spaced 10 cm apart, with dots added for every remaining space between the marks. When the push rod must be advanced 10 cm, corresponding to a 5 cm length of balloon folding, each marking 131 visible in the transparent distal portion 167 indicates a successful 5 cm length of balloon folding. Markings of various thicknesses, different colors, and different numbers may be used in the same manner as described for the combination of stripes and dots. In certain embodiments, colored sections may be added to the balloon to indicate the degree of balloon folding.

[0056] Additional embodiments of the present invention for feedback markers that allow the extent of positive balloon folding to be externally visible to a physician outside the patient's body include the use of a thread with knots or stitches, spaced at known increments to provide tactile feedback of the progress of the balloon folding. The knots or stitches may be radiopaque. The thread may have color-coded regions to provide feedback to the operator. FIG. 34 shows a thread 140 with a series of knots or stitches 142 according to an embodiment of the present invention. The balloon 130 may be transparent to enhance the visibility of the thread, knots, or stitches. In certain embodiments, the knots or stitches may constitute an additional cell collection surface.

[0057] A further feedback mechanism of the present invention involves ultrasonic saline-air markings and a sine wave pattern for the balloon, with the distance between the maxima of the sine wave defining the pitch of the balloon folds.

[0058] Any patent document or publication mentioned in this specification is 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 an example of a particular embodiment of the present invention but is not intended to be limiting in its practice. [Explanation of symbols]

[0059] 1 Fallopian tube 10. Introducer catheter (a tube that can be positioned in the fallopian tube) 12 Non-elastic sleeve (balloon) 14 Elastic balloon (balloon) 202 Handle 204 Drive Wheel 206 Push Wire 220 Internal handle gear mechanism (actuator) 222 Drive gear (first gear) 226 Idle Gear 228, 230, 232 1st gear to 3rd gear (2nd gear to 4th gear)

Claims

1. A catheter, a tube having a distal end; a balloon having a proximal end and a distal end, the balloon coupled to the distal end of the tube at the proximal end of the balloon and movable between a first folded position and a second unfolded position; further comprising a push wire attached to the balloon; an actuator including a gear that actuates the push wire; a drive wheel mechanically coupled to the gear of the actuator; The drive wheel includes a boss inserted into the first gear of the actuator, the push wire is positioned between the first gear and the second gear and between the third gear and the fourth gear, the first gear drives an idle gear and the second gear, the idle gear drives the third gear which drives the fourth gear, and by driving the first gear, advances the push wire.

2. The catheter of claim 1 , further comprising a source of pressurized fluid in selective communication with the balloon.

3. The catheter of claim 1 further comprising a handle.

4. The catheter of claim 1 , wherein when the balloon is deflated, a series of wrinkles form on the surface of the balloon, creating multiple edges for collecting cells.

5. A catheter, a tube having a distal end; a balloon having a proximal end and a distal end, the balloon coupled to the distal end of the tube at the proximal end of the balloon and coupled to the distal end of the tube at the proximal end of the balloon, the balloon being movable between a first folded position and a second unfolded position; further comprising a push wire attached to the balloon; an actuator including a gear that actuates the push wire; a sheath coaxial with the tube, the sheath extending outward from the distal end and covering a folded first length of the balloon; The balloon has a smaller diameter lead balloon tip at the distal end of the balloon in the folded back second position, the lead balloon tip being flexible and having a blunt edge.

6. 6. The catheter of claim 5, further comprising a thin-walled tube extending outward from the distal end and enclosed by the folded first length of the balloon, the thin-walled tube providing support and straightening to the first length.

7. A catheter, a tube having a distal end; a balloon having a proximal end and a distal end, the balloon coupled to the distal end of the tube at the proximal end of the balloon and coupled to the distal end of the tube at the proximal end of the balloon, the balloon being movable between a first folded position and a second unfolded position; further comprising a push wire attached to the balloon; an actuator including a gear that actuates the push wire; a feedback mechanism for measuring the positive fold back of the balloon; The balloon has a smaller diameter lead balloon tip at the distal end of the balloon in the folded back second position, the lead balloon tip being flexible and having a blunt edge.

8. 8. The catheter of claim 7, wherein the feedback mechanism includes visual markers on the balloon, the visual markers being spaced at a predetermined pitch or of different colors along the balloon.

9. A catheter, a tube having a distal end; a balloon having a proximal end and a distal end, the balloon coupled to the distal end of the tube at the proximal end of the balloon and coupled to the distal end of the tube at the proximal end of the balloon, the balloon being movable between a first folded position and a second unfolded position; further comprising a push wire attached to the balloon; an actuator including a plurality of gears that actuates the push wire; and at least one knotted thread or stitch on the outer surface of the balloon in the folded-back position, the knotted thread or the stitches configured to collect cells in contact therewith; the actuator further includes a drive wheel mechanically coupled to a plurality of gears of the actuator, the plurality of gears including a first gear, a second gear, a third gear, a fourth gear, and an idler gear, the drive wheel including a boss inserted into the first gear; the push wire is positioned between the first gear and the second gear and between the third gear and the fourth gear; The first gear drives the idle gear and the second gear, and the idle gear drives the third gear and the fourth gear, rotating the first gear and thereby advancing the push wire.

10. The catheter of claim 9 , wherein the knot or stitch is radiopaque.

11. 10. The catheter of claim 1, further comprising a small diameter lead balloon tip on the distal end of the balloon in the folded back position.

12. 10. The catheter of claim 1, further comprising a fluoropolymer or silicone coating that lubricates a forward portion of the catheter for entry into a stenosis in a patient.

Images