阅读说明：本技术 用于活检和细胞学检查的子宫外翻导管的设备和方法 (Apparatus and method for an everting uterine catheter for biopsy and cytological examination ) 是由 史蒂文·R·巴茨奇 马修·托马斯·尤瑞克 皮乌士·维迪亚西 于 2019-07-23 设计创作，主要内容包括：本发明公开了一种外翻球囊系统,其可用于在患者或动物体内进行活检。外翻球囊系统可用于进入体腔或脉管,以在特定身体位置收集组织样本。所描述的外翻导管系统简化了组织活检的过程。(An everting balloon system is disclosed that may be used for taking biopsies in a patient or animal. Everting balloon systems may be used to access a body cavity or vessel to collect a tissue sample at a particular body location. The described everted catheter system simplifies the procedure of tissue biopsy.)

1. An apparatus for detaching tissue from a remote location, comprising:

an elongate element having a lumen and a distal end, wherein the distal end has a first transverse port in communication with the lumen, and wherein a distal tip of the elongate element is closed; and

an everting membrane radially outward of the elongate element, wherein the everting membrane has a first proximal configuration and a second distal configuration, and wherein in the first configuration the distal end of the everting membrane is proximal to the transverse port, and wherein in the second configuration the everting membrane covers the transverse port.

2. The apparatus of claim 1, further comprising a suction source in fluid communication with the lumen.

3. The apparatus of any of the preceding claims, further comprising a cutting wire extending through the lumen, wherein the wire has a longitudinal axis and a first protrusion at a distal end of the cutting wire, the first protrusion extending laterally away from the longitudinal axis, and wherein the wire has a first configuration in which the first protrusion is entirely inside the lumen and a second configuration in which the first protrusion extends laterally out of the first lateral port; and wherein the cutting wire is configured to rotate about the longitudinal axis, and wherein the cutting wire changes from the first configuration to the second configuration during rotation about the longitudinal axis.

4. A method for removing a tissue sample from a uterus, comprising:

inserting a distal end of an elongate member into the uterus, wherein the elongate member has a receiving space for receiving a tissue sample, wherein the receiving space has an opening and a lid closable over the opening, and wherein the opening comprises a port on a side of the elongate member;

placing the tissue sample in the elongated element; and

closing the lid over the opening.

5. The method of claim 4, further comprising, after closing the cap, transferring the receiving space through a cervix and out of the uterus through a vagina, wherein the transferring comprises keeping the cap closed while the receiving space is transferred out of the uterus through the cervix and through the vagina.

6. The method of claim 4 or 5, wherein the displacing of the accommodation space comprises displacing the elongated element.

7. The method according to any one of claims 4 to 6, wherein said displacing of said accommodation space comprises displacing said elongated element simultaneously with said accommodation space.

8. A method according to any one of claims 4 to 7, wherein the lid comprises an everting member, and wherein the transfer of the accommodation space comprises inverting or everting the lid.

9. A method according to any one of claims 4 to 8, wherein the cap comprises an everting member.

10. The method of any one of claims 4 to 9, wherein the closing of the lid comprises inverting or everting the lid over the opening.

11. The method of any one of claims 4 to 10, further comprising separating the tissue sample from tissue in the uterus adjacent to the tissue sample.

12. The method of any of claims 4-11, wherein the opening comprises a port at a side of the elongated element.

13. The method of any one of claims 4 to 12, further comprising taking a biopsy of a uterus, resulting in the tissue sample being separated from the uterus, and wherein taking the biopsy comprises placing the tissue sample.

14. The method of any one of claims 4 to 13, further comprising separating the tissue sample from surrounding tissue with a wire, wherein the wire is at least partially in the elongated element.

15. The method of any one of claims 4 to 14, wherein placing the tissue comprises applying suction through the opening.

16. A method for removing a tissue sample from a uterus, comprising:

inserting a distal end of an elongate element into the uterus, wherein the elongate element has a closed distal end and a receiving space containing the tissue sample, wherein the receiving space has an opening, and wherein an everting member is attached to the elongate element, wherein the everting member has a first configuration and a second configuration, and wherein in the first configuration the distal end of the everting member is proximal to the opening, and wherein in the second configuration the distal end of the everting member is distal to the opening;

placing the tissue sample in the elongated element; and is

Covering the opening, wherein the covering comprises moving the everting member from the first configuration to the second configuration.

17. A method according to claim 16, wherein the movement of the everting member comprises eversion or inversion.

18. The method according to claim 16 or 17, further comprising, after covering the opening, transferring the accommodation space out of the uterus through a cervix and through a vagina, wherein the transferring comprises holding the distal tip of the everting member away from the opening while the accommodation space is transferred out of the uterus through the cervix and through the vagina.

19. The method of any of claims 16-18, wherein the opening comprises a port at a side of the elongated element.

20. A method according to any one of claims 16 to 19, wherein in the first and second configurations the entire everting element is radially outward of the elongate element.

Background

The present application has particular utility with everting catheters characterized by having an inner catheter, an outer catheter and an everting membrane connected to both catheters. The inner catheter may contain a lumen to pass fluids or media, drugs or therapeutic agents, instruments or devices (such as IUDs, endoscopes) and other catheters.

Access systems for vessels and body cavities within a patient typically use various guide wire and catheter techniques or everting catheters for physicians and medical professionals. Everting catheters utilize the balloon inversion traversing action and roll or evert through vessels using a propulsive force under the influence of hydraulic pressure created by a compressible or incompressible fluid or medium from inside to outside. Everting balloons have been referred to as rolling or abduction balloons, everting membranes, local interventional radiology catheters or linear everting catheters, such as those in U.S. patents 5,364,345, 5,372,247, 5,458,573, 5,472,419, 5,630,797, 5,902,286, 5,993,427, 6,039,721, 3,421,509, and 3,911,927, among others, all of which are incorporated herein by reference in their entirety. These are classified as everting balloons and are used to pass through vessels, lumens, ducts or tubes in a frictionless manner. In other words, the everted balloon may pass through the duct without exerting any shear forces on the wall of the tube being passed through. Due to this action and the absence of shear forces, the resulting trauma may be reduced and the risk of perforation reduced. In addition, due to the mechanism of travel through the vessel, materials and substances in the proximal portion of the duct or vessel are not pushed or advanced forward to the more distal portion of the duct or vessel.

In addition, as the everting catheter is deployed from the inside out, uncontaminated or untouched balloon material is placed inside the vessel wall. In the inverted or undeployed state, the balloon is contained within the catheter body and is inaccessible to the patient or physician. As the balloon is pressurized and everted, the balloon material rolls from the inside out without contacting any elements outside the vessel. Another advantage of everting balloon catheters is that the access method is more comfortable for the patient because the hydraulic force "pulls" the balloon membrane through the vessel or duct as opposed to standard catheters that need to be "pushed" in and through the vessel or duct.

The everting catheter is described as a dilatation catheter. Representative examples of dilating everting catheters include U.S. patent application nos. 5,364,345 and 4,863,440, which are incorporated herein by reference in their entirety.

The eversion catheter also describes additional elements such as a handle for controlling instruments within the eversion catheter. A representative example is U.S. patent application No. 5,346,498, which is incorporated herein by reference in its entirety. The everting balloon catheter may be comprised of an inner catheter having an inner lumen or through lumen (or through lumen). The through lumen may be used for passage of instruments, media, materials, therapeutic agents, endoscopes, guide wires, or other instruments or devices. Representative examples of everting catheters with a through lumen are described in U.S. patent application nos. 5,374,247 and 5,458,573. In addition, everting catheters have been described as having a waist or narrowed balloon diameter, such as in U.S. patent application No. 5,074,845, which is incorporated by reference herein in its entirety.

Disclosure of Invention

More specialized eversion catheter systems have specific instruments or tools built into the catheter system. Examples of such tools or instruments are biopsy devices, cytological examination devices, drug delivery mechanisms, endoscopes, IUDs or other tools to be delivered into a body cavity, body space, potential body space created by an everting balloon mechanism or body vessel. There are several advantages to having the instrument built into the eversion catheter system. The everted balloon can be used to pull the instrument into the body cavity without requiring the physician or operator to push the instrument into place. This is useful for tortuous or tight passages or any pathway in which the everting balloon serves to protect the body passage from the distal profile of the instrument as it is pulled to the desired location. The biopsy device is fixed to the everting catheter system and automatically extends beyond the distal end of the everting balloon by being pulled into the body cavity by the everting balloon or for endometrial biopsy in the uterine cavity. During eversion, the biopsy device is isolated from the body tissue until it extends beyond the distal end of the everting balloon. This is particularly useful in uterine biopsies because vaginal, endocervical, or other more proximal tissue is not picked up or contaminated into the biopsy device. Providing a biopsy device at a particular distance in an everting catheter system may provide a physician with the ability to guide a biopsy to a particular location. Other embodiments described herein show how biopsies are performed at specific locations in a body cavity or cavity. As an example, some embodiments may perform a biopsy specifically in the front of the lumen to provide the physician with more targeted information about the patient's condition. Other examples of locations include posterior, lateral, contralateral, multiple locations, or disease or diagnostic progression from a proximal portion of the body lumen versus a more distal portion. Biopsy may be provided by aspiration systems, cytological examinations, tissue removal, tissue collection, body fluid or material collection, or by providing diagnostic tools in vivo to indicate the presence of pH, temperature, pressure, or certain chemicals, materials, bile, blood, or other bodily materials. Once a tissue or cell biopsy is taken in vivo, the everting catheter system may be removed and the everting catheter may be everted again to retrieve the collected tissue sample.

One embodiment of a everted catheter for performing biopsy procedures is a suction mechanism or additional derivative mechanism built into the distal end of the inner catheter. Additional derivative mechanisms include configurations for performing specific tissue removal procedures on the desired tissue sample type.

Additional embodiments include a suction mechanism that defines a larger area in the body cavity for a wider range of tissue collection. Another embodiment includes automatically rotating the innerduct during the eversion and inversion steps for larger area tissue collection.

Another improvement is to automate the aspiration step when fully everted.

Further improvements include mechanisms for performing aspiration either in a one-handed manner or by activating the aspiration source with one button.

Another example is that the everting catheter used to perform the biopsy is a cell or tissue brush built into the distal end of the inner catheter. One embodiment describes a cytobrush or tissue brush that works with an eversion balloon to capture tissue within the bristles during eversion.

Both examples of biopsies described above show everted catheter systems during the inversion or retraction process, which can perform the biopsy at a specific location in the body without exposing the biopsy mechanism to a proximal or undesired part of the body passage. This is advantageous in situations where a specific location, orientation or uncontaminated tissue sample is required.

Another embodiment of an everted catheter for performing a biopsy is an instrument that performs tissue shaving and removal. Another embodiment for shaving and collecting tissue includes a mechanism designed to sweep through a larger area for tissue collection at a desired location in the body.

Another embodiment of the everting catheter comprises an everting balloon membrane surface specifically designed to pick up and collect tissue or cells at a location within the body. The everted film comprises an outer surface having protruding hooks, latches, barbs or bristles that collect tissue or cells when the everted film is deployed and exposed in a particular area. Another embodiment comprises a material with microchannels or pores on the outer surface of the everted membrane that press against the tissue and pick up cellular material when everted. Upon inversion, the tissue collection area is drawn into the everting membrane where it is contained and protected from contamination by other areas of the body passageway. Once the everting catheter system is removed from the body, the everting catheter may be everted again to expose the tissue collection area for tissue sample retrieval. In one configuration, the tissue collection region may be distal to the everting membrane at a fully everted position. Other configurations may have the tissue collection area of the membrane near or closer to the distal end of the everted membrane. Another configuration may have a tissue collection area through multiple radial segments or strips to biopsy different locations of a body passageway, which may facilitate checking the extent or spread of a disease state. In addition, tissue collection areas may be placed at anterior and posterior locations of the everted membrane to define specific locations of cells or tissues of interest.

Another embodiment for the exclusive collection of body fluids in a specific location of the body has a porous everted or fluid receiving membrane or material for fluid collection lining the outer surface. Upon eversion, the fluid collection area of the everting membrane will come into contact with a specific body location within the passageway or body cavity.

Another embodiment has an everted balloon membrane with diagnostic material on its outer surface. The diagnostic material may be designed to determine pH, lactate, hormone content, drug content, urine, feces, blood, lymph, bile, mucus, infection or pus, edema, or other detectable body fluids or byproducts. The diagnostic material may be placed as a test strip on the outer surface of the everted membrane. Other forms of test strips may detect and report the temperature of exposure, the amount of pressure applied, such as in a pressure sensitive test strip, or the internal surface morphology of tissue within a body vessel.

Another embodiment may include a through lumen within the inner catheter for irrigating or irrigating tissue to facilitate collection of cells or samples. Increased flushing may facilitate collection of cells, for example obtaining endometrial cells for determination of endometrial receptivity for an in vitro fertilization procedure.

Another embodiment may include a tissue agitator on the everting membrane to facilitate collection of tissue or cells. Another embodiment has a tissue agitator on the inner catheter of the biopsy device that automatically performs an agitation function when everted or inverted. The physician or operator may manually advance or retract or rotate the entire everting catheter system to facilitate tissue agitation, thereby increasing the amount of tissue used for sample collection.

The device can be used for atrophic endometrium or postmenopausal women. The device may include a tissue razor for removing and collecting a thin layer of tissue within the uterine cavity.

The tissue shaver may have an external collection device and an internal collection device with and without internal suction.

The tissue razor may include an internal coring device.

The tissue shaver may include a cell collection and filtration system, which may include an irrigation source for the uterine cavity.

A method of extracting a tissue sample from a uterus is disclosed. The method may include inserting a distal end of an elongate member into a uterus, placing a tissue sample in the elongate member, and closing a cover over the opening. The elongate member may have a receiving space, such as a receptacle or lumen of the elongate member, to receive the tissue sample. The receiving space may have an opening and a lid that is closable over the opening. The opening may have or may be a port on a side of the elongate member.

The method may include transferring the containment space out of the uterus, through the cervix, and through the vagina after closing the cap. The lid may remain or continue to close as the receiving space exits the uterus, passes through the cervix and through the vagina. The displacing of the accommodation space may comprise displacing the elongated element. The displacing of the accommodation space may comprise displacing the elongated element simultaneously with the accommodation space. The lid may have or may be an everted member. The transfer of the receiving space may comprise turning the lid in or out. Closing the lid may include inverting or inverting the lid (e.g., an everting member such as a membrane) over the opening.

The method may include separating the tissue sample from tissue adjacent the tissue sample within the uterus. The opening may have or may be a port on a side of the elongate member.

The method may include performing a biopsy of the uterus, thereby separating the tissue sample from the uterus. The taking of a biopsy may include placement of a tissue sample.

The method can include separating the tissue sample from surrounding tissue with a wire, wherein the wire is at least partially within the elongate member. The positioning of the tissue may include suctioning the opening. Suction may pull the tissue sample into the lateral port and into the lumen of the elongate member.

A method for retrieving a tissue sample from a uterus is disclosed that may include inserting a distal end of an elongate element into the uterus, placing a tissue sample in the elongate element, and covering an opening. The elongate member may have a closed distal tip and a receiving space, such as a lumen or a container, for receiving the tissue sample. The receiving space may have an opening, such as one or more lateral ports on the elongate member.

The everting member may be attached to the elongate element. The everting member may have a first contracted configuration and a second extended configuration. In the first configuration, the distal end of the everting member may be proximal to the opening. In the second configuration, the distal tip of the everting member may be distal to the opening. Covering the opening may include moving the everting member from the first configuration to the second configuration. In the first configuration and the second configuration, the entire everting element may be radially outside the elongate element.

An apparatus for separating tissue from a remote location is disclosed. The device may have an elongated member and an everting membrane. The elongate member may have a lumen and a distal tip. The distal tip may have a first transverse port in communication with the lumen. The distal tip of the elongated element, e.g., the distal surface, may be closed or have no ports or fenestrations.

The everting film may be radially outward of the elongate member. The everting membrane may have a first proximal configuration and a second distal configuration. In the first configuration, the distal end of the everting membrane may be adjacent to the transverse port. In the second configuration, the everting membrane may create a fluid seal, cover, block, or otherwise occlude the side port.

The apparatus may have a suction source in fluid communication with the lumen. The device may have an irrigation source connected to the lumen. The lumen may have an irrigation channel. The irrigation source may be connected to the irrigation channel.

The device may have a cutting line extending through the lumen. The wire may have a longitudinal axis and a first tab at a distal end of the cutting wire. The first protrusion may extend laterally away from the longitudinal axis. The wire may have a first configuration in which the first protrusion is entirely inside the lumen and a second configuration in which the first protrusion extends laterally out of the first lateral port. The cutting wire may be configured to rotate about a longitudinal axis. During rotation about the longitudinal axis, the cutting line may change from the first configuration to the second configuration.

The device may have an everting member radially outward of the elongate element.

The distal tip of the elongate element may have a second transverse port. The cutting line may have a second protrusion. The second protrusion may be entirely inside the lumen when the wire is in the first configuration. The second protrusion may extend laterally out of the second lateral port when the wire is in the second configuration.

The wire may have a distal tip. The distal tip may be in contact with an inner surface of the lumen. Pressing the wire longitudinally may press the distal tip against the inner surface of the lumen. The wire may then be deformed, biased, or displaced (e.g., deformed or undeformed) into a second configuration.

The first and/or second protrusions may have a V-shape.

Drawings

Fig. 1A to 1F show an everted catheter with a suction mechanism for performing a biopsy procedure.

Fig. 2A-2F show additional derivations built into the distal end of the inner catheter in side and top views.

Figures 3A and 3F show in side and top views a suction mechanism that expands or defines a larger area within the body cavity for a wider range of tissue collection once the biopsy device exits the distal end of the everted membrane.

Figure 4 shows the automatic rotation of the innerduct during eversion and inversion steps for larger area tissue collection.

Fig. 5A to 5C show another modification of automatically performing the suction step after eversion.

Fig. 6A to 6C show a further modification of the device including a mechanism for performing suction in a one-handed manner.

Fig. 7A and 7B show other examples of everted catheters for taking biopsies, which comprise a cytobrush built into the distal end of the inner catheter.

Figures 8A to 8D show an eversion catheter for performing a biopsy, comprising a cytobrush built into the distal end of the inner catheter, whereby the cytobrush works with the eversion balloon as a system to capture tissue within the bristles of the cytobrush during the eversion process.

Fig. 9A-9D illustrate everted catheters for performing biopsies with an instrument that performs tissue shaving and removal.

Fig. 10A and 10B illustrate everted catheters for performing biopsies with an instrument for performing tissue shaving and removal and a mechanism designed to sweep over a large area for tissue collection in a desired location in the body.

Figures 11A-11D show in cross-section an everting catheter with an everting balloon membrane surface having protruding hooks, latches, barbs or bristles to pick up and collect tissue or cells at a location in the body.

Figure 12 shows in cross-section an everting balloon catheter with material on the outer surface of the distal end of the everting membrane having microchannels or micropores that are pressed against tissue when everted to pick up cellular material.

Figure 13 shows in cross-section an everting balloon catheter with material on the outer surface near or closer to the distal end of the everting membrane having microchannels or micropores that are pressed against tissue when everted to pick up cellular material.

Figure 14 shows in cross-section an everting balloon catheter with material on the outer surface of the everting membrane, the material having multiple tissue collection areas by radial segments or strips to facilitate biopsy of different locations of the body passageway, which may facilitate examination of the extent or spread of a disease state.

Figures 15A-15E illustrate an everting balloon catheter having a material on the outer surface of the everting membrane, wherein the material has a plurality of tissue trapping regions placed at anterior and posterior locations on the everting membrane to define specific locations of cells or tissue of interest in a body passageway.

Figures 16A and 16D show an eversion balloon catheter with material for collecting body fluids at a specific location in the body, whereby the everting membrane is lined on the outer surface with a porous or fluid-receiving membrane or material for collecting fluids to collect body fluids at a specific body location within a passageway or body cavity.

Fig. 17A and 17B illustrate an everting balloon catheter having an everting balloon membrane with diagnostic materials on the outer surface for determining pH, lactate, hormone content, drug content, urine, feces, blood, lymph, bile, mucus, infection or pus, edema, or other detectable body fluids or byproducts.

Figure 18 shows an everting balloon catheter with an everting balloon membrane having diagnostic material on the outer surface that can detect and report the temperature of exposure, the amount of pressure applied as in a pressure sensitive test strip, or the internal surface morphology of tissue within the body vessel.

Figure 19 shows a biopsy eversion catheter system including a through lumen within the inner catheter for irrigation or lavage of tissue to facilitate cell or sample collection.

Fig. 20 shows in cross-section a biopsy eversion catheter system with a tissue stirrer on the everting membrane to facilitate tissue or cell collection.

FIG. 21 shows a biopsy eversion catheter system with a tissue agitator on the inner catheter of the biopsy device that automatically performs the agitation function when everted or inverted.

Fig. 22 shows a biopsy eversion catheter system with a handle for manually advancing or retracting or rotating the entire eversion catheter system to facilitate tissue agitation, thereby increasing the amount of tissue used for sample collection.

Fig. 23A-23C show a tissue razor for removing and collecting thin layers of tissue within the uterine cavity, which may be used in atrophic endometrial or postmenopausal women.

Fig. 24 shows a tissue shaver with an internal cutting device with internal suction in a cross-sectional view.

Fig. 25 illustrates a tissue razor that may include an internal coring device.

Fig. 26A and 26B illustrate in cross-section a tissue collector that may include a mechanism for cell collection and sampling.

Detailed Description

An everting balloon system (also referred to as an everting catheter system) is disclosed that may be used to traverse a vessel, such as a cervical canal, to perform a biopsy procedure. An everting balloon system may be used to access the uterine cavity through the cervix. The cervical canal is a single lumen vessel that can be stretched or dilated. The eversion catheter system may also be passed through other locations within the patient or animal for tissue collection purposes.

Fig. 1A to 1F show an everted catheter with a suction mechanism for performing a biopsy procedure. FIG. 1A shows a biopsy device housed in an everted catheter system 10 in an everted membrane position. The everted membrane and biopsy device (not visible in this figure) are contained within an outer catheter 18, with an acorn tip 10 at the distal end. The acorn tip 19 has an opening (not visible) at the distal end. At the proximal end of the outer catheter 18 is a T-joint or Y-joint 17, which contains an X-ring gasket (not visible). The expansion tube and plug valve 15 provide hydraulic energy to the eversion conduit system. May be supplied by brine, air, brine and air mixture, or by a gas such as CO₂Contrast media, culture media gas, and other fluids to provide hydraulic energy. The inner catheter 16 may be passed within the outer catheter 18 to advance and retract the everting membrane (not visible). At the proximal end of the inner catheter 16 is a proximal hub 20 designed to connect a syringe plunger 22 to a suction source such as a syringe 21. Other sources of suction may be wall vacuum, portable vacuum sources, syringe motor systems, and other manually driven inflators driven by ratchet and screw plungers.

FIG. 1B shows the distal end of biopsy device 30 in a fully everted position or when the everted membrane (not visible in this view) is fully everted. The biopsy device 30 has a rounded distal end 32 and a side hole 31. Possible additional side holes 31 may include an opening at the distal end of the device, or a combination of both side and distal holes. In operation, when biopsy device 30 is in a body cavity, such as the uterine cavity, a suction source may draw tissue, media, cellular matter, and other bodily fluids into side aperture 31. When used in conjunction with an irrigation source or lavage, the side holes 31 can be used to collect bodily materials and irrigation fluid. The side holes 31 may be used to deliver other fluids into the body cavity, such as contrast media, echogenic fluids, and drugs or therapeutic fluids.

Fig. 1C shows the proximal end of the biopsy device with everted catheter 10, with outer catheter 18 attached to Y-fitting 17 and inflation tube and stopcock 15. The inner catheter (not visible) may be in a fully everted position and housed within the outer catheter 18. The proximal hub 20 may be connected by a user to the syringe 21 with the plunger 22 in the retracted position to provide a source of negative pressure or suction.

Fig. 1D shows the distal end of the outer catheter 18 and the acorn tip 19 with the eversion membrane 25 passing through the distal opening of the acorn tip 19 at the initial stage of eversion. The everting membrane 25 may roll from the inside out in response to hydraulic energy. The advancement of the everting membrane 25 may be performed by a user transferring an inner catheter (not visible) or automatically in response to hydraulic energy.

Figure 1E shows the continuation of the eversion process, wherein the eversion film 25 has advanced further beyond the acorn tip 19. At this point in the eversion process, the distal end of biopsy device 30 and distal rounded tip 32 may protrude from the end of everting membrane 25. During endometrial biopsy, everting membrane 25 may advance 1cm to 5cm before biopsy device 30 protrudes from everting membrane 25 to approximate the length of the endocervical canal. Other biopsy devices may be advanced a distance of 2cm to 4cm or 3cm before the biopsy device protrudes from the distal end of the everted membrane. Other biopsy devices may be made with a translatable or repositionable outer tube (not shown) to adjust the distance traveled by the everting membrane within the endocervical canal before the biopsy device protrudes from the distal end of the everting membrane.

Figure 1F shows the everted membrane 25 in a fully everted state and extending beyond the acorn tip 19. Biopsy device 30 can be seen to have a side hole 31 and a rounded distal end 32. The biopsy device is flexible, has dimensions of 1mm to 4mm, or 2mm to 3mm in diameter, and is made of nylon elastomer (Pebax), polyurethane, polypropylene, teflon, nylon, or other biological material. For endocervical tubes, the everting membrane is sized to be 1mm to 5mm in diameter, or 2mm to 4mm, or 3mm, and 0.001mm to 0.004mm, or 0.0015mm in wall thickness. The everting membrane may be made of radiation polyolefin, polyurethane, nylon elastomer (Pebax), silicone or other flexible film material. The side hole 31 has an elliptical opening of 0.5mm in the minor axis and 2.5mm in the major axis. The opening size may also be circular, with an opening inner diameter in the range of 0.5mm to 4.0mm, or 2.5 mm. In conjunction with the side hole 31, negative pressure is supplied by the syringe 21 as a suction source. By applying negative pressure, tissue or bodily material is collected within the side aperture 31 of the biopsy device 30. The negative pressure is also relieved by pressurization of the everting membrane 25, which membrane 25 contacts the body cavity or, in the case of a uterine biopsy, the endocervical canal to maintain an airtight seal within the uterine cavity. Also in conjunction with the negative pressure, the physician may advance and retract the entire everting catheter system 10 to additionally pull tissue into the side hole 31. The motion of advancing and retracting the everting catheter system 10, while in the uterine cavity, ranges from 0.5cm to 2.0cm in a back and forth manner. The everting catheter system 10 may also be rotated while in the body or uterine cavity. During the application of negative pressure, or in conjunction with the physician's movement on the everting catheter system 10, tissue is drawn into the biopsy device 30 and the inner catheter 16. Biopsy device 30 and inner catheter 16 may be constructed of a translucent or optically transparent material, such as natural polypropylene, natural nylon elastomer (natural Pebax), Teflon, or other translucent or optically transparent biocompatible materials that allow the physician to view the tissue that is drawn into biopsy device 30.

Fig. 2A-2F show additional derivations built into the distal end of the inner catheter in side and top views. Fig. 2A shows a side view of the distal end of an elongated biopsy device 30, which may have a flexible cylindrical tube with a closed rounded distal tip 32 and a lateral port or side hole opening 31. Additional side holes may be formed on the biopsy device, including an opening at the distal end of the biopsy device. The side hole opening 31 also includes an agitator member 35 designed to disrupt or agitate the surface of the tissue in the body cavity, passage or lumen to produce more cellular material for collection or for disruption of the endometrium. In another application, it may be desirable to agitate the endometrium for a period of time prior to embryo transfer during in vitro fertilization. In operation, a suction source is applied to biopsy device 30 and tissue, fluid, cells, or other bodily material is drawn into biopsy device 30.

Fig. 2B shows a top view of biopsy device 30 showing agitator member 35 at a location distal to side hole opening 31. Stirrer member 35 may be configured as a bump, barb, hook, or roughened surface, and it is designed to break tissue when biopsy device 30 is advanced, retracted, or rotated about its axis. Fig. 2A and 2B show the agitator member at the distal end of the side hole 31, but the agitator member may have a continuous or perforated ridge configuration at the proximal end, at both ends, or over the entire circumference of the side hole.

Fig. 2C and 2D illustrate another type of biopsy device 30 having a side hole opening 31 and a rounded end 32. The side surface of the side hole opening 31 has the agitator member 36 only at one side position, but both sides can receive the agitator member.

Fig. 2D further shows the position of the agitator member 36 on the side of the side hole 31 in a top view. In this configuration, agitator member 36 is designed to break tissue as biopsy device 30 is rotated about its central axis.

Fig. 2e and 2F show another form of side hole opening 31 angled to the central axis of biopsy device 30. Agitator members 37 are placed on the side walls and distal end of the side hole opening 31 and are designed to break tissue as the biopsy device 30 is advanced, retracted, and rotated within the body cavity.

Figures 3A and 3F show in side and top views a suction mechanism that expands or defines a larger area within the body cavity to collect a wider range of tissue once the biopsy device exits the distal end of the everted membrane. Fig. 3A shows the distal end of biopsy device 30 after exiting the distal end of the everted membrane. The distal end of biopsy device 30 has a flexible, resilient flared portion 41 and opens to a larger diameter after it is not contained within the eversion film. This expansion may be achieved using a resilient inner material that allows bending, such as nitinol struts (not shown), and a flexible material such as silicone, polyurethane, or other biocompatible flexible material that responds to the bending provided by the nitinol struts. The struts may be constructed of other materials such as spring steel, Elgiloy (Elgiloy) or other polymers that may be used as living hinges.

FIG. 3B illustrates the effect of everting membrane 25 on the distal end of biopsy device 30, where flared portion 41 is compressed to a lower profile within the everting membrane.

Fig. 3C shows a top view of the dilating portion 41 of the biopsy device 30, as well as the configuration of the side hole opening 31 fully open when the biopsy device is extended beyond the everted membrane (not visible).

Figure 3D shows the effect of the everting membrane 25 on the configuration of the dilating portion 41 and the side hole opening 31. Note that the side hole opening 31 is now almost closed under the influence of the everting membrane 25 on the now compressed dilating portion 41.

Fig. 3E and 3F show biopsy device 30 in a fully extended position outside of the everted membrane (not shown). In the extended position, biopsy device 30 has a bend 42 near the distal end of biopsy device 30, and side hole opening 31 has a rounded tip 32. In operation, the bend 42 is straightened within the eversion film in a straight profile. Once extended beyond the everting membrane, bend 42 defines a larger area as biopsy device 30 is advanced, retracted, or rotated within the body. The bend 42 may be formed from a shape memory material, such as nitinol, as an internal support material or mandrel (not shown), or by thermoforming or molding into a polymeric material of the biopsy device 30 to form the bend 42.

Fig. 3F illustrates biopsy device 30 with bend 42 in a top view to illustrate that the bend can be in a variety of configurations and represents a three-dimensional curve in the x, y, and z axes.

Fig. 4 shows in top view the automatic rotation of the inner catheter during the eversion and inversion steps for larger area tissue collection. The biopsy device 30 extends fully from the everting membrane (not shown) and is configured similar to an auger cork screw such that the side hole 31 rotates about the central axis of the biopsy device 30 as it is advanced and retracted to provide a larger area of tissue collection within the body.

Fig. 5A to 5C show another modification of automatically performing the suction step after eversion. Fig. 5A shows a biopsy device having everted catheter 10, with biopsy device 30 extending beyond everted membrane 25, in a fully everted position, with an inner catheter (not visible) housed within outer catheter 18. Proximal hub 20 is adjacent to Y-joint 17 with inflation tube and stopcock 15. The syringe 21 is connected to the proximal hub 20, and the syringe plunger 22 and spring 54 are in compression between the flange 51 and the proximal portion of the syringe plunger 22. The clip 52 holds the spring in compression by being trapped in the flange 51 and connector 53.

Fig. 5B shows a close-up view of the syringe 21 with the compression spring 54 and clip 52 retained by the flange 51. The spring 54 may be made of stainless steel, spring steel, or a polymer. The clip 52 may be made of a polymer or metal and may be configured as a latch, strap, or tab that mechanically retains the spring 54 compressed.

Fig. 5C shows the spring 54 now extended, with the clip 52 separated from the flange 51. When disengaged, the spring 52 acts on the syringe plunger 22 to provide a source of suction for the syringe 21 within the biopsy device. By moving, flipping, displacing or otherwise manipulating the clip 52 away from the flange 51 or mechanical locator on the flange 51, the physician or user can automatically provide a source of suction without the need to use two hands to displace the clip 52 from the flange 51, as the syringe plunger 22 will be withdrawn and pulled back from the syringe 21 under the influence of the action of the spring or the force of the spring 54 to provide the source of suction. Other embodiments may include clips 52 that are retained on the flange 51 by a sliding button, hook, notch, or depressible button or detent (all not shown). In operation, these embodiments for moving the clip 52 provide a one-handed operation for automatically supplying the suction source with negative pressure to draw the syringe plunger 22 by the spring action or force of the spring 52.

Fig. 6A to 6C show a further modification of the device including a mechanism for performing suction in a one-handed manner. Fig. 6A shows another biopsy device with everted catheter 10 in a fully everted position, with biopsy device 30 extending beyond everted membrane 25. A suction ball 70 having an air check valve 71 is connected to the proximal hub 20.

Fig. 6B shows the user squeezing the suction bulb 70, which expels air from the suction bulb through the air check valve 71.

Fig. 6C shows the user releasing the compression on the suction bulb 70, which creates a suction source through the biopsy device with the everted catheter 10. The squeezing or compression is repeated and the suction bulb 70 is then released to continue to draw pressure within the system. Other embodiments for supplying a single-handed suction source include a mechanical flywheel, a ratchet-controlled pump, or a battery-operated pump.

Fig. 7A and 7B show other examples of everted catheters for taking biopsies, which comprise a cytobrush built into the distal end of the inner catheter. Figure 7A shows a cytobrush within an eversion catheter 11 with an eversion membrane 25. The cell brush 61 has a rounded distal end 65 with brushes, bristles, absorbent material, hooks, barbs, or other protrusions designed to collect tissue, cells, fluid, or other bodily material. The cytobrush with everted catheter 11 has a knob 71 for rotating, advancing or retracting the distal end of the cytobrush 61. The tee 70 has a flush tube 72 for supplying fluid, media, gas or other material through a connector hub 73 and out of the eversion membrane 25 through the device. The Y-joint with stopcock 15 is used to provide hydraulic pressure to the eversion catheter system.

FIG. 7B shows two different configurations of cytobrushes 61 and 62. The size of the cytobrush may be 1mm to 5mm in outer diameter and 0.5cm to 3cm in length for use in the uterine cavity. Other dimensions are possible for other locations in the body. The cytobrush may be configured to be in a straight state, malleable to bend (not shown), have a preset bend (not shown), or shaped as a loop or lasso (not shown).

Fig. 8A-8D illustrate an everting catheter for performing a biopsy, which may include a cytobrush built into the distal end of the inner catheter, whereby the cytobrush works with the everting balloon as a system to capture tissue within the bristles during the inversion process. Fig. 8A shows a cytobrush 80 that may have a distal end 81 with segmented bristles 82, 83, and 84 and exposed locations 90 and 91. The cytobrush 80 may extend completely beyond the eversion membrane 25. In operation in a body cavity or site, full extension of the cytobrush 80 may allow tissue contact of the segmented brushes 82, 83 and 84. The number of segmented brushes can be from 2 to a number suitable for cytobrushes. For example, for a uterine cavity application, the cytobrush 80 may have 3 to 6 segmented brush sites, wherein each site is 3-4mm in length and 2 to 4mm in diameter.

Fig. 8B shows that the cytobrush 80 can be retracted into the everting membrane 25 with the proximal segmented brush position 82 flattened under the influence of the everting membrane. When the segmented brush locations 82 are flattened, the bare locations 90 become collection points for tissue, cells, fluids, and other bodily materials. Subsequently, as the cytobrush 80 continues to retract into the everting membranes 25, the segmented brush locations 83 will flatten and capture tissue and bodily materials in the exposed locations 91.

FIG. 8C shows an alternative configuration of a cytobrush 100 having segmented brushes in a spiral configuration with a continuous spiral brush 102 and exposed locations 90, 91 and 92. The bare locations are continuous in nature but are marked separately for clarity.

Figure 8D shows the cytobrush retracted within everting membrane 25, wherein the proximal portion of spiral brush 102 is compressed or flattened and tissue or bodily material is collected at the exposed location 90.

Fig. 9A-9D illustrate everted catheters for performing biopsies with an instrument that performs tissue shaving and removal. A tissue razor with an everted catheter 90 is shown having an open razor 91 with a razor distal end 92. The razor 91 is open when extended from the everted membrane 25 and the razor 91 is closed or in a low profile state (not shown) when the razor 91 is retracted within the everted membrane 25. The proximal knob 99 allows for advancement, retraction, or rotation of the razor 91. The razor 91 may be made of metal, nitinol, or a polymer.

Fig. 9B shows a close-up view of the razor 91 and the razor end 92 extending beyond the distal end of the everted membrane 25 with the acorn-shaped tip 19. The razor 91 may also be constructed from a composite material on the razor 91 with a silicone, polyurethane or other coating on the razor 91. The coating is configured to have a roughened surface (not shown) or to contain protrusions (not shown) to collect or capture tissue within the opening of the razor 91. In another embodiment, a coating may be placed on the distal portion or distal half of the razor (not shown) to capture tissue as the razor is closed and retracted.

Fig. 9C shows another razor with everted catheter 105 opened and deployed to a larger area within the body using razor 93 with distal end 94. The razor 93 is in the open position after leaving the everted film 25, which is completely everted and beyond the acorn tip 19. The everted catheter is completely everted when the inner catheter (not visible) is displaced within the outer catheter 18 through the Y-fitting 17 under the influence of hydraulic pressure applied through the inflation tube and the stopcock 15. A knob 98 connected to the proximal hub 25 may be used to advance, retract and rotate the razor 93 at the distal end of the razor with everted catheter 105. At the proximal end of the knob 98 is a luer connection 97 with a through bore for connection with a syringe (not shown) for injection of irrigation fluid, contrast media, saline, gas, air or therapeutic agents during surgery. Luer connection 97 may also be used to provide a source of suction (not shown) to help retain cells, fluids, or other bodily materials during tissue shaving and collection or when the device is withdrawn from the body.

Fig. 9D is a close-up view of razor 93 with distal end 94 extending beyond the distal end of everted membrane 25. The razor 93 is made of stainless steel, but other materials such as nitinol, Elgiloy or polymeric materials such as polypropylene, polycarbonate, ABS, nylon, PEEK or other biocompatible materials are possible.

Fig. 10A and 10B illustrate an everted catheter for performing a biopsy with an instrument to perform tissue shaving and removal and a mechanism designed to sweep over a larger area for tissue collection within a desired location within the body. Fig. 10A shows the distal end of everted membrane 25 having razor 96 with distal end 95.

Fig. 10B shows the shaving razor 96 opening and deploying beyond the everted membrane 25, with the shaving elements 95 configured to remove tissue within the body. The razor 96 may be advanced, retracted, and rotated by a physician or user. Upon retraction into the everted membrane 25, the razor 96 contracts and returns to a low profile.

Figures 11A-11D show cross-sectional views of an everting catheter having an everting balloon membrane surface with protruding hooks, latches, barbs, or bristles to pick up and collect tissue or cells at a location in the body. In this embodiment, the everting membrane itself becomes the test or tissue collection tool by physically contacting the everting membrane with a body cavity, passage, lumen or potential space. Figure 11A shows a cross-sectional view of eversion membrane 125 fully everted from an eversion catheter (not shown). The distal end of the everted membrane 125 contains bristles 126 or brushes on the surface of the membrane. Bristles 126 pick up or collect tissue, cells, or bodily material as the membrane is everted and rolled over the tissue surface. When the everting membrane 126 is retracted and inverted along the central axis of the everting catheter system, the bristles 126 roll into the everting membrane 125 and collect the cellular material. Note that by definition, the tissue collection or tissue sampling area is limited to the area where the everted membrane 125 and the tissue collection elements or bristles 126 are in contact.

Figure 11B shows a close-up cross-sectional view of the front side of the everting film 125 and bristles 126.

Fig. 11C shows a cross-sectional view of one side of the everted membrane 125 with another embodiment of a tissue or cell collection system comprised of hooks 127 or barbs. Once deployed, the hooks 127 contact and collect tissue that will be captured within the everting membrane 125 upon completion of the everting process.

Fig. 11D shows a cross-sectional view of the side of the everting membrane 125 showing an alternative tissue collection element having a tissue collection element comprised of latches 128 and 129, the latches 128 and 129 opening and closing upon physical contact with tissue. When everted, the latches 128 and 129 close and capture tissue or cellular material.

Figure 12 shows a cross-sectional view of an everting balloon catheter (not shown) having cell collecting material 136 on the outer surface of the distal end of the everting membrane 135, the cell collecting material 136 having microchannels 137 or pores which are pressed towards the tissue when everted to collect cellular material. In operation, the everting membrane 135 is deployed within the body lumen until the portion with the cell trapping material 136 contacts the tissue. Upon application of pressure using everting membrane 135, microchannels 137 open and collect bodily material. Upon eversion, the device's microchannels 137 and cell trapping material 136 are partially retracted within the everting membrane 135.

Figure 13 shows a cross-sectional view of an everting balloon catheter (not shown) having cell trapping material 136 on the outer surface near or closer to the distal end of the everting membrane 135, the cell trapping material 136 having microchannels 137 or pores which press against tissue when everted to pick up cellular material. This embodiment shows that the cell collection material 136 can be placed at a specific location on the everting membrane 135 that is not at the distal end of the membrane or on a specific side of the everting membrane, including the anterior, posterior, lateral, or a combination of these locations.

Figure 14 shows in cross-section an everting balloon catheter (not shown) with cell trapping material 136 at various locations on the outer surface of the everting membrane 135. Multiple regions of tissue collection material 136 may be defined by radial segments or strips to biopsy different locations of a body passageway, which may facilitate or determine the extent of spread of a disease state in a body cavity. As an example, using an eversion process of the everting membrane 135, the cell collection material 136 in the more proximal portion of the evaluation device relative to the more distal portion may provide the practitioner with a rate of disease progression or treatment.

Figures 15A-15E illustrate an everting balloon catheter having tissue collecting material 326 on the outer surface of an everting membrane 325, wherein multiple regions of tissue collecting material 326 are placed at anterior and posterior locations on the everting membrane to assess the specific location of the cell or tissue of interest in the body passageway. Figure 15A shows an initial stage of the eversion process in which the everting film 325 exits the acorn tip 19 and the film rolls at the distal end 320 with the tissue collection material 326 located in the everting film 325.

Figure 15B shows the eversion process wherein the everting film 325 is further away from the acorn tip 19 and the tissue collection material 326 is rolled out of the distal end 320 of the everting film 325.

Fig. 15C also shows the tissue collection material 326 rolling out on both sides of the everting membrane 325 at the distal end 320.

Figure 15D shows completion of the eversion process, wherein the everting film 325 is fully everted and the tissue collection material 326 is visible on one side of the everting film 325.

Figure 15E shows tissue collection material 326 positioned on either side of everting membrane 325 to provide the ability to assess or diagnose two different areas, such as the anterior and posterior, or the lateral and contralateral, of a body cavity or passage.

Figures 16A and 16D show an eversion balloon catheter with material for collecting body fluids at a specific location in the body, whereby the everting membrane is lined on the outer surface with a porous or fluid-receiving membrane or fluid-collecting material to collect body fluids at a specific body location within a passageway or body cavity. Figure 16A shows an initial stage of the eversion process in which the eversion film 325 extends from the distal opening of the acorn tip 19. The distal end 320 of the everting film is visible and the tissue collecting material 327 is located and isolated within the everting film 325.

Figure 16B shows the eversion process continuing with further advancement of the everting film 325 from the acorn tip 19 and the tissue collection material 327 just exiting the distal end 320 of the everting film 325.

Figure 16C shows completion of the eversion process with tissue collection material 327 on one side of everting membrane 325 and just proximal to distal end 320.

Figure 16D shows the same tissue collection material 327 in another view on one particular side of the everted membrane 325. Providing the tissue collection material 327 at a particular distance and at a particular location on the everted membrane 325 provides the ability to directly diagnose a particular or particular region in a body passageway or lumen. Since the eversion membrane 325 operates without shear forces or sliding along the inner surface of the body during eversion, the tissue collection material 327 will be exposed within the body only to the tissue contacting the material.

Fig. 17A and 17B show an everting balloon catheter with an everting balloon membrane 325 having diagnostic material 328 on the outer surface for determining pH, lactate, hormone content, drug content, urine, feces, blood, lymph, bile, mucus, infection or pus, edema, or other detectable body fluid or by-product. The diagnostic material 328 can be seen to be located just near the distal end 320 of the everted membrane 325 extending beyond the acorn tip 19. Fig. 17A and 17B show the diagnostic material 328 located at a particular location on the everting membrane 325, but a variety of diagnostic materials (not shown) or diagnostic materials that surround the entire circumference or outer surface of the everting membrane (not shown) are also possible.

In another embodiment, fig. 18 shows an everting balloon catheter with an everting balloon membrane 325 with diagnostic material 329 on the outer surface of the everting membrane 325 that can detect and report the temperature of exposure, the amount of pressure applied as in a pressure sensitive test strip, or the internal surface morphology of tissue within the body vessel. As an example, pressure sensitive adhesive tape is used as the diagnostic material 329 everted into the body passageway. Once everted, the hydraulic pressure within the eversion catheter system may be increased to facilitate the pressure sensitive tape to contact the tissue at a known pressure. The amount of internal hydraulic pressure may be reduced to subsequently allow inversion and removal from the patient's body. After removal, the pressure sensitive tape or diagnostic material may be evaluated. Other types of assessment include internal tissue morphology or temperature.

Fig. 19 shows a biopsy eversion catheter system 12 that includes a through lumen within an inner catheter (not visible) to irrigate or lavage tissue through port 73 and tubing 72. The lavage fluid or fluid exits the everted membrane 25 at the distal end 62 near the biopsy device 61 (shown here with a cell brush, but other biopsy instruments are possible) to facilitate cell or sample collection.

Fig. 20 shows in cross-section a biopsy eversion catheter system with tissue stirrers 201 and 202 on the everting membrane 200 to facilitate tissue or cell collection. Once everted from the everting membrane 200, the tissue stirrers 201 and 202 are exposed to the tissue. Tissue agitators 201 and 202 may also be used in conjunction with physically advancing, retracting, or rotating the entire everting catheter system

Fig. 21 shows a biopsy eversion catheter system with a tissue stirrer 210 on the inner catheter of the biopsy device 201, the tissue stirrer 210 automatically performing a stirring function when everted or everted. Tissue agitator 210 is designed to loosen or disrupt tissue for collection in side hole opening 215 of biopsy device 201.

Fig. 22 shows a biopsy eversion catheter system 700 having a handle 705 for manually advancing, retracting, or rotating the entire eversion catheter system to facilitate tissue agitation, thereby increasing the amount of tissue used for sample collection. The physician or operator can use the handle button 706 to physically evert or invert the eversion membrane (not visible in the outer catheter 18). Alternatively, a handle button may be attached to biopsy device 701 for single manual advancement, retraction, or rotation of the biopsy device.

Fig. 23A-23C show in cross-section a tissue shaver 800 for removing and collecting thin layers of tissue within the uterine cavity, which is particularly suitable for atrophic endometrial or postmenopausal women. The tissue shaver 800 has a distal catheter 805, which may have side holes 808 and 809, with an internal nitinol wire 810 located in the lumen of the distal catheter 805.

Fig. 23A illustrates a variation of the configuration of the inner nitinol wire 810 when the tissue shaver 800 may be placed within a uterine cavity or body cavity. Fig. 23B shows that once placed within the uterine cavity or other body cavity, a nitinol wire 810 may be advanced within the lumen of the distal catheter 805. When advanced, the nitinol wire protrusions 811 and 812 may exit the side holes 808 and 809 for exposure within the endometrium 900 or other tissue defined by the body lumen. The nitinol wire protrusions 811 and 812 may be configured to cut or shave tissue as the distal catheter 805 is rotated within the tissue or endometrium 900.

Fig. 23A and 23B show the distal catheter 805 with two side holes 808 and 809, but may have a single side hole and a greater number of side holes. The side holes may be configured to be diametrically opposed to each other or co-linear on the surface of the distal catheter 805, as shown in fig. 23A and 23B. In operation, the distal catheter 805 may be placed within the patient out of an eversion membrane (not shown) or as a single cannula catheter.

Fig. 23C shows a biasing force 813 on the inner nitinol wire 810, which may force the nitinol wire protrusions 811 and 812 out of the side holes 808 and 809. As the inner nitinol wire 810 is advanced within the lumen of the distal catheter 805, a biasing force 813 may act on the lumen surface 814 to force the nitinol wire protrusions 811 and 812 out of the side holes 808 and 809.

Fig. 24 shows in cross-section a tissue shaver 815 with an internal cutting wire 820 that may be housed within the lumen of the distal catheter 816. The lumen of the distal catheter 816 can be coupled with an internal suction source (not shown) that supplies vacuum pressure 822 that forces endometrial or body cavity tissue (not shown) within the side holes 817. The cutting wire 820 may be coupled to an actuator or motor on the proximal portion of the catheter (not shown) that rotates the cutting wire 820 within the lumen of the distal catheter 816. The distal end of the cutting wire 820 is shown with a distal cutting wire ball 821 capable of facilitating movement of the cutting wire 820 within the lumen of the distal catheter 816. In operation, once deployed in the uterine cavity or body cavity, suction or vacuum force 822 may be applied to force the endometrium and body cavity tissue within the side hole 817. In combination, rotation of the cutting wire 820 can cut tissue protruding into the interior of the side hole 817. The cutting wire 820 can be configured with a biasing force 824 and a wire bend 826 to force the cutting portion 828 to cut tissue at the side hole 817. Alternatively, the tissue shaver 815 may be used without the vacuum force 822 or internal suction source.

Fig. 24 shows one side hole 817, but multiple side holes at different locations on the distal catheter 816 are possible. The cutting wire 820 may be configured as a coil or spring (not shown). The coil or spring may be made of round wire, flat wire, D-shaped wire, or a multi-faceted wire surface. As a coil or spring, the cutting wire mechanism can be rotated within the lumen of the distal catheter, or advanced and retracted, either individually or in combination, to provide a cutting surface at the side hole of the distal catheter. This cutting action may be performed with or without vacuum force.

Fig. 25 shows, in cross-section, a tissue shaver 830, which may include an internal coring screw 835 within a distal catheter 832 having a side hole 834. The lumen of the distal catheter 832 may be coupled to a suction source (not shown) that supplies a vacuum force 836. In operation, when the distal catheter 832 is placed within a uterine cavity or body cavity, a vacuum force 836 may be applied to force endometrial or body cavity tissue within the side hole 834. Optionally in combination, an actuator or motor (not shown) at the proximal end portion of the tissue shaver 830 may be coupled to the internal coring screw 835 to provide rotation 838 to the internal coring screw 835, which may be rotated with or independently of the distal catheter 832. The internal coring screw 835 may comprise a pitch wherein the threads 839 and 840 remove endometrial and body cavity tissue when the internal coring screw 835 is rotated. The endometrial and body cavity tissue may be driven toward the proximal portion of the distal catheter 832, along with the rotation of the internal coring screw 835 and the vacuum force 836, to a sample collection area (not shown) in the proximal portion of the tissue shaver 830 as the side holes 834 are removed. The internal coring screw 835 and the tissue shaver 830 may be used without a coupled suction source. The distal catheter 832 may have multiple side holes at different locations on the distal catheter. For sample collection, after removal from the uterine cavity or body cavity, an actuator or motor may be applied in the opposite direction to push the endometrial and body cavity tissue back toward the side hole 834 for removal from the distal catheter 830.

Fig. 26A and 26B illustrate in cross-section the tissue collector 840 with the distal catheter 842, wherein the irrigation lumen 846 may be coupled to an irrigation source (not shown) operated by a user or physician that provides irrigation 847 through the irrigation side aperture 843. The fluid medium used for flushing 847 may include saline or culture medium depending on the application. The distal catheter 842 may have an aspiration side hole 844 that may be connected to an aspiration lumen 848. A suction source (not shown) at the proximal portion of the tissue collector may provide a vacuum force 849. Near the suction side holes 844, the filter membrane 850 may be porous for collecting cells or tissue of a certain size. The filter membrane may include 0.2 to 15 micron filtration pores or other pores, for example to drive a vacuum or pressure differential through the filter membrane 850, but leave cells or tissue contents on the distal side 851 of the filter membrane. In operation, once the distal catheter 842 is placed within a uterine or body cavity, media 847 may be introduced through the irrigation lumen 846 and out into the patient through the irrigation side hole 843. A vacuum force 849 may be applied within the suction lumen 848 to drive the contents from the uterine cavity or body cavity into the suction side holes 844. The filter membrane 850 may capture tissue or cellular contents on the distal side 851 of the filter membrane 850. The distal catheter 842 may then be removed from the patient. To obtain a tissue or cellular sample, the distal catheter 842 may be configured with a perforation or preferably weak point 852 that allows an end user to break the filter membrane 850 off of the distal catheter 842 for subsequent analysis of the collected tissue or cellular contents. The suction side holes 844 can be used as portals to retrieve harvested tissue. The tissue collector 840 can be used without the irrigation lumen 846 and irrigation media 847. Multiple side irrigation holes may be employed. Multiple side aspiration holes, or a combination of several side irrigation and aspiration holes, may be used. Multiple filtration membranes can be used in which different porosities are used. For example, the distal-most or first filter membrane may have a greater porosity while the second, more proximal filter membrane has a smaller or finer porosity to collect a particular size of tissue or cells that will flow through the first filter membrane. The inlet may be between the first and second membranes, for example for recovering collected tissue or cells between the two filtration membranes. A perforation or preferably a weak point in the distal catheter may for example withdraw tissue or cells between the two filter membranes. Multiple filter membranes may be used.

Fig. 26B shows the tissue collector 840 in cross-section, with the tissue collector 840 having a tissue or cell collection region 860 at a proximal portion of the tissue collector. The suction source 862 can provide a vacuum force 849 through the tissue or cell collection area 860, through the filter membranes 871 and 870, and finally through the suction lumen 848 to the distal catheter 842 and the suction side port 844. The tissue or cell collection area 860 can be removed by the user after a sampling procedure, during which the cap 864 can be removed to access the sample in the collection area 861. The irrigation lumen 846 may provide media 847 through the irrigation side holes 843 and a filtration system that includes an irrigation source for the uterine cavity. As shown in FIG. 26A, the tissue collector 840 shown in FIG. 26B may be used without the irrigation lumen 846 and irrigation medium 847. Multiple side irrigation holes may be employed. Multiple side aspiration holes, or a combination of several side irrigation and aspiration holes, may be used.

Any of the apparatus and/or method elements described herein may be used in conjunction with the application No. 61/302,742 filed on 11/2013; application No. 61/977,478 filed on 9/4/2014; application No. 62/005,355 filed on 30/5/2014; application No. 62/528,422 filed on 3.7.2017; application No. 62/553,057 filed on 31/8/2017; application No. 62/007,339 filed on 3/6/2014; and any apparatus and/or method elements of U.S. provisional application No. 62/597,353 filed 2017, 12, 11, all of which are hereby incorporated by reference in their entirety.

Any element described herein as singular can be plural (i.e., any element described as "a," "an," or "the" can be more than one). Any element of a genus element may have the characteristics or elements of any other element of the genus. The medium transferred herein can be any fluid described herein (e.g., a liquid, a gas, or a combination thereof). The patents and patent applications cited herein are all incorporated by reference in their entirety. For purposes of clarity, some elements may be absent from the various figures. The above-described configurations, elements or complete assemblies and methods for performing the present disclosure, and elements thereof, as well as variations of aspects of the present disclosure, may be combined with and modified with each other in any combination. All of the devices, apparatus, systems and methods described herein can be used for medical (e.g., diagnostic, therapeutic or rehabilitation) or non-medical purposes.