Tissue sample devices and methods

Abstract

A tissue sampling system for obtaining a sample from a body, the system including an outer tubular member having a proximal end region and a distal end region and defining a lumen extending from the proximal end region to the distal end region, an inner tubular member slidably disposed within the lumen of the outer tubular member, the inner tubular member defining a lumen extending from the proximal end region to the distal end region of the inner tubular member, and a tissue sampling device disposed adjacent the distal end region of the inner tubular member.

Description

[Technical Field]

[0001] FIELD OF THE INVENTION This application relates generally to medical devices for tissue sampling, and more particularly to medical devices for tissue sampling that increase the yield of cells or other tissue. [Background technology]

[0002] Certain medical tests require sampling cells from a target area of ​​a subject's body. For example, a screening test to detect potential precancerous and cancerous tissues in a subject's body may include taking a tissue or cell sample from a target area of ​​the subject's body. A tissue collection device can be used to collect cells or other tissues from the target area. Sampling tissue from some anatomical structures can be difficult. There is a continuing need to provide alternative medical devices and alternative methods for manufacturing and using medical devices. Summary of the Invention

[0003] The present disclosure provides design, material, manufacturing method, and use alternatives for medical devices. In a first embodiment, the tissue sampling system includes an outer tubular member having a proximal end region and a distal end region and defining a lumen extending from the proximal end region to the distal end region, an inner tubular member slidably disposed within the lumen of the outer tubular member, the inner tubular member defining a lumen extending from the proximal end region to the distal end region of the inner tubular member, and a tissue sampling device disposed adjacent the distal end region of the inner tubular member, the inner tubular member being movable between a retracted delivery position and an advanced sample sampling position.

[0004] Alternatively, or in addition to any of the above examples, in another example, the tissue sampling device may be disposed about the outer surface of the inner tubular member. Alternatively, or in addition to any of the above examples, in another example, the tissue harvesting device may be removably coupled to the distal end region of the inner tubular member.

[0005] Alternatively, or in addition to any of the above examples, in another example, the distal end region of the inner tubular member may include a linkage mechanism. Alternatively or additionally to any of the above examples, in another example, the coupling mechanism of the inner tubular member may include multiple threads.

[0006] Alternatively, or in addition to, any of the above examples, in another example, the tissue harvesting device may include an elongate shaft extending from a distal end region to a proximal end region and defining a lumen extending from the distal end region to the proximal end region.

[0007] Alternatively, or in addition to any of the above examples, in another example, the proximal end region of the tissue harvesting device may include a linkage mechanism. Alternatively or additionally to any of the above examples, in another example, the coupling mechanism of the tissue harvesting device may include multiple threads.

[0008] Alternatively, or in addition to, any of the above examples, in another example, the coupling mechanism of the tissue harvesting device can be configured to be removably coupled to the coupling mechanism of the inner tubular member. Alternatively, or in addition to, any of the above examples, in another example, the tissue harvesting device may further include a sealing mechanism positioned adjacent to and extending radially from the proximal end region of the tissue harvesting device.

[0009] Alternatively, or in addition to, any of the above examples, in another example, the tissue harvesting system may further comprise an atraumatic distal tip member disposed distally of the tissue harvesting device. Alternatively, or in addition to, any of the above examples, in another example, at least a portion of the atraumatic distal tip member can be configured to contact the distal end of the outer tubular member when the inner tubular member is in the retracted delivery configuration.

[0010] Alternatively, or in addition to any of the above examples, in another example, the tissue sampling device may include a brush mechanism. Alternatively or additionally to any of the above examples, in another example, the brush mechanism may include a plurality of radially extending bristles.

[0011] Alternatively, or in addition to, any of the above examples, in another example, the plurality of radially extending bristles may be grouped into a plurality of brush clusters. Alternatively, or in addition to, any of the above examples, in another example, the tissue harvesting system may further include a guidewire, which may be configured to be coaxially disposed with the inner tubular member and slidably disposed within the lumen of the inner tubular member.

[0012] In another example, a tissue collection system may include an outer tubular member having a proximal end region and a distal end region and defining a lumen extending from the proximal end region to the distal end region, an inner tubular member slidably disposed within the lumen of the outer tubular member, the inner tubular member defining a lumen extending from the proximal end region to the distal end region of the inner tubular member, and a tissue collection device disposed about and extending radially from the distal end region of the inner tubular member, The inner tubular member may be movable between a retracted delivery position and an advanced sample collection position.

[0013] Alternatively, or in addition to any of the above examples, in another example, the tissue sampling device may include a brush mechanism. Alternatively, or in addition to, any of the above examples, in another example, the tissue harvesting system may further comprise an atraumatic distal tip member disposed distally of the tissue harvesting device.

[0014] Alternatively, or in addition to, any of the above examples, in another example, at least a portion of the atraumatic distal tip member can be configured to contact the distal end of the outer tubular member when the inner tubular member is in the retracted delivery configuration.

[0015] In another example, a tissue collection system may include an outer tubular member having a proximal end region and a distal end region and defining a lumen extending from the proximal end region to the distal end region, an inner tubular member slidably disposed within the lumen of the outer tubular member, the inner tubular member defining a lumen extending from the proximal end region to the distal end region of the inner tubular member, and a tissue collection device removably coupled to the distal end region of the inner tubular member, The inner tubular member may be movable between a retracted delivery position and an advanced sample collection position.

[0016] Alternatively, or in addition to, any of the above examples, in another example, the tissue sampling device may include an elongate shaft extending from a distal end region to a proximal end region and defining a lumen extending from the distal end region to the proximal end region, a brush mechanism extending radially from an outer surface of the elongate shaft, and an atraumatic distal tip member disposed adjacent the distal end region.

[0017] Alternatively, or in addition to any of the above examples, in another example, the proximal end region of the tissue harvesting device may include a linkage mechanism. Alternatively, or in addition to, any of the above examples, in another example, the coupling mechanism of the tissue harvesting device can be configured to be removably coupled to a mating coupling mechanism of the inner tubular member.

[0018] The above summary of some exemplary embodiments is not intended to describe each disclosed embodiment or every implementation of the present invention. [Brief explanation of the drawings]

[0019] The present invention may be more fully understood by considering the following detailed description of various embodiments in conjunction with the accompanying drawings. [Figure 1] 1A-1C show partial cross-sectional side views of an exemplary tissue harvesting device system for delivering a tissue harvesting device to a target area in a retracted or delivery configuration. [Figure 2]2 illustrates a partial cross-sectional side view of the exemplary tissue harvesting device system shown in FIG. 1 with the tissue harvesting device in a deployed or harvesting configuration. [Figure 3] 10 shows a cross-sectional view of a distal end region of another exemplary tissue harvesting device delivery system. [Figure 4] 4 is an exemplary flowchart of a method for obtaining a tissue sample using the system of FIGS. 1-3.

[0020] While the invention is susceptible to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit aspects of the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. DETAILED DESCRIPTION OF THE INVENTION

[0021] All numerical values, whether explicitly stated or not, are assumed to be modified herein by the term "about." The term "about" generally refers to a range of numbers that one of ordinary skill in the art would consider equivalent to the recited value (i.e., having the same function or result). In many instances, the term "about" can indicate that a number is rounded to the nearest significant figure.

[0022] The recitation of numerical ranges by endpoints includes all numbers within that range (eg, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5). Although certain preferred dimensions, ranges and / or values ​​for various components, features and / or specifications are disclosed, those skilled in the art stimulated by this disclosure will understand that the desirable dimensions, ranges and / or values ​​may deviate from those expressly disclosed.

[0023] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term "or" is generally used in its sense to include "and / or" unless the content clearly dictates otherwise.

[0024] The following detailed description should be read with reference to the drawings, in which similar elements in different drawings are numbered the same. The detailed description and drawings, which are not necessarily to scale, depict exemplary embodiments and are not intended to limit the scope of the invention. The exemplary embodiments shown are intended as examples only. Selected features of the exemplary embodiments may be incorporated into additional embodiments, unless expressly indicated to the contrary.

[0025] Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure that utilizes both endoscopic and fluoroscopic techniques to diagnose and treat problems occurring in the common bile duct (CBD) and pancreatic duct (PD). One of the main problems treated today is strictures in the CBD due to, but not limited to, primary sclerosing cholangitis (PSC), cholangiocarcinoma, and gallstone damage and scarring within the bile duct. ERCP has now matured primarily as an interventional procedure. When clinicians need to obtain samples from strictures, one of the most common ways to do this is with a cytology brush.

[0026] Currently, there is no satisfactory cytology brush mechanism for obtaining cell samples from common bile duct strictures. Clinicians may use stricture brushing with or without intraductal aspiration of bile. However, aligning the brush over the stricture often remains problematic. The tip of the mechanism often does not pass through the ampulla and / or stricture. Current tissue collection devices or brushes may include devices with snub-nose outer catheter tips. A guidewire may be advanced through a separate channel in the catheter adjacent to the brush rather than inside the brush. As a result, during insertion, the catheter tip has difficulty navigating curved surfaces and strictures and tends to impinge on the outer surface of bends. Tissue collection devices and systems that enable the tip of the delivery catheter and tissue collection device to easily pass through ampulla, bends, and strictures may be desirable. While the present disclosure is described with respect to the common bile duct and pancreatic duct, the devices and methods are not limited to such use. For example, the devices and methods described herein may be used in any part of the anatomy as desired. Additionally, the devices and methods described herein may be used in either endoscopic or non-endoscopic anatomies, some exemplary anatomies including, but not limited to, the mouth, esophagus, stomach, duodenum, other parts of the gastrointestinal tract, the pathway to the lungs, other parts of the respiratory system, the urinary tract, the cervix, other reproductive anatomies, etc.

[0027] FIG. 1 is a partial side cross-sectional view of an exemplary tissue collection device system 10 for delivering a tissue collection device 12 to a target region, such as, but not limited to, the common bile duct or pancreatic duct, in a retracted or delivery configuration. The tissue collection system 10 can include an outer or external elongate shaft or tubular member 14 and an inner elongate shaft or tubular member 16. The inner tubular member 16 can be slidably disposed within a lumen 18 of the outer tubular member 14. The outer tubular member 14 can extend proximally from a distal end region 20 to a proximal end region 22 configured to remain outside the patient's body. A first hub or handle 24 can be coupled to the proximal end region 22 of the outer tubular member 14. In some cases, a port 50, such as an injection port, can be provided on the outer tubular member 14. Other structures can be provided to facilitate connection to other medical devices (e.g., syringes, stopcocks, Y-adapters, etc.) and provide access to the lumen 18. The inner tubular member 16 may extend proximally from a distal end region 26 to a proximal end region 28 configured to remain outside the patient's body. A second hub or handle 30 may be coupled to the proximal end region 28 of the inner tubular member 16.

[0028] The outer tubular member 14 may include a lumen 18 extending from the distal end region 20 to the proximal end region 22. The lumen 18 may also extend through the first handle 24. The lumen 18 of the outer tubular member 14 and the first handle 24 may be configured to slidably receive the inner tubular member 16. The inner tubular member 16 may include a lumen 40 extending from the distal end region 26 to the proximal end region 28. The lumen 40 of the inner tubular member 16 may also extend through the second handle 30. The lumen 40 of the inner tubular member 16 may be configured to receive a guidewire 42, if desired.

[0029] The distal end region 26 of the inner tubular member 16 may include an atraumatic distal tip member 32. The atraumatic distal tip member 32 may be sized and shaped to facilitate advancement of the inner tubular member 16 and tissue collection device 12 through bends and strictures. The atraumatic distal tip member 32 may include a body 33 having a proximal end 34, a distal end 36, and an intermediate region 38. The body 33 may be solid, and the lumen 40 of the inner tubular member 16 extends through the body 33. The cross-sectional dimension of the atraumatic distal tip member 32 in a direction generally perpendicular to the longitudinal axis of the inner tubular member 16 may vary along the length of the atraumatic distal tip member 32. For example, the cross-sectional dimension may increase distally from the proximal end 34 toward the intermediate region 38 and decrease from the intermediate region 38 toward the distal end 36. Stated another way, the maximum cross-sectional dimension of the atraumatic distal tip member 32 may be at or near the intermediate region 38. It is envisioned that such a configuration may allow the proximal end 34 of the atraumatic distal tip member 32 to be disposed within the lumen 18 of the outer tubular member 14 during delivery and removal of the device. The intermediate region 38 may have a cross-sectional dimension similar to or greater than the inner diameter of the outer tubular member 14 such that the intermediate region 38 may abut, contact, or abut the distal end region 20 of the outer tubular member 14 and seal off the lumen 18 of the outer tubular member 14. This may help reduce sample loss during retraction of the system 10, as described in more detail herein.

[0030] The tissue collection device 12 may be disposed around a portion of the inner tubular member 16 at or adjacent the distal end region 26 of the inner tubular member 16. The tissue collection device 12 may extend around the entire circumference of the inner tubular member 16. In other embodiments, the tissue collection devices 12 may be radially spaced around the circumference of the inner tubular member 16 in a uniform pattern or an eccentric manner, as desired. In some embodiments, the tissue collection device 12 may include a brush mechanism including a plurality of bristles 46. While the tissue collection device 12 is described as a brush mechanism, it is contemplated that other tissue collection devices may be used, as desired. The bristles 46 may extend radially outward from the outer surface of the inner tubular member 16. The bristles 46 may be arranged in a first brush cluster 44a, a second brush cluster 44b, and a third brush cluster 44c (collectively 44). Although the tissue collection device 12 is shown as including three longitudinally spaced brush clusters 44, the tissue collection device 12 may include fewer than three (e.g., one or two) or more than three (e.g., four, five, six, or more) brush clusters 44. The bristles 46 may be bonded, glued, or otherwise secured to the outer surface of the inner tubular member 16. In some cases, the bristles 46 may be directly bonded to the outer surface of the inner tubular member 16. Alternatively, the bristles 46 may be secured to one or more collars or rings, which are in turn bonded to the outer surface of the inner tubular member 16. The collars or rings may be solid components or may comprise multiple wires twisted together to form a cylindrical tube, in which case it is envisioned that the bristles 46 may be clamped between the multiple twisted wires.

[0031] The bristles 46 may be employed to brush against a tissue surface within a target area to capture cells. The bristles 46 may be disposed / mounted about a distal portion of the inner tubular member 16. In some embodiments, each of the bristles 46 may have a substantially circular cross-section. However, the bristles 46 may have any other suitable cross-sectional shape, including rectangular, triangular, square, polygonal, elliptical, or oval.

[0032] The bristles 46 may be made of one or more filaments. For example, the multiple bristles 46 may be made of a continuous length of filament. Alternatively, the multiple bristles 46 may be made of discrete lengths of filament. The filament may be a monofilament. The monofilament may be formed by extrusion. Alternatively, the filament may be a multicomponent filament. A multicomponent filament may include a core with one or more layers of material concentrically arranged. If multiple layers are present, they may differ in composition and / or thickness. The outermost layer may include micropatterning, as described in more detail below. A multicomponent filament may be formed by coextrusion. It is contemplated that the filament may be made of nylon, polymer, and / or any suitable material or combination of materials.

[0033] It is contemplated that the bristles 46 may be arranged in any desired configuration. In some cases, the bristles 46 may be arranged helically around the distal portion of the inner tubular member 16 or may extend radially outward from the inner tubular member. In some embodiments, the bristles 46 may radiate at an angle relative to the longitudinal axis of the inner tubular member 16. It is further contemplated that the density of the bristles 46 may vary along the length of the tissue collection device 12 or between clusters 44a, 44b, 44c. In some cases, the length of the bristles 46 may vary. When the bristles 46 are rubbed against tissue in the target area, cells from the tissue may be transferred to the bristles 46 and trapped between the bristles 46.

[0034] When the tissue collection device 12 is disposed within the outer tubular member 14, the tissue collection device 12 may be constrained in a reduced-diameter, compressed or delivery configuration by the outer tubular member 14 surrounding the tissue collection device 12. In the compressed configuration, the tissue collection device 12 may have a smaller diameter than in the expanded, deployed configuration. The distal end region 20 of the outer tubular member 14 may be positioned such that the outer tubular member 14 surrounds and wraps the length of the tissue collection device 12 during delivery. The outer tubular member 14 may have sufficient hoop strength to hold the tissue collection device 12 in its reduced-diameter state.

[0035] 2 is a partial cross-sectional side view of the exemplary tissue collection device system 10 of FIG. 1 , with the tissue collection device 12 in a deployed or collection configuration. The tissue collection system 10 can be advanced through the body toward a target site as desired. The tissue collection system 10 can be advanced with or without a guidewire 42. Once the tissue collection device 12 is positioned adjacent to the target area, the restraining forces maintaining the tissue collection device 12 in a radially compressed configuration are removed, allowing the tissue collection device 12 to be deployed.

[0036] The tissue collection device 12 can be deployed by actuating the second handle 30, e.g., by pushing the second handle 30 distally, while maintaining the first handle 24 in a fixed position. Thus, the inner tubular member 16 can be advanced distally relative to the outer tubular member 14. In other words, the inner tubular member 16 can be advanced distally while the outer tubular member 14 is stationary. The reverse configuration is also contemplated. For example, the outer tubular member 14 can be retracted proximally while the inner tubular member 16 is stationary. As shown in FIG. 2 , when the inner tubular member 16 is advanced distally, the biasing force is removed from the outside of the tissue collection device 12, and the tissue collection device 12 assumes its radially expanded, unbiased, deployed configuration.

[0037] As can be seen in FIG. 2 , the first brush cluster 44a and the third brush cluster 44c have a first height, and the second brush cluster 44b has a second height that is greater than the first height. It is contemplated that other height combinations of bristles 46 or brush clusters 44 may be used as desired. For example, the height of the bristles 46 may increase in a tapered, sloped, or stepped manner in the distal direction. Alternatively, the height of the bristles 46 may decrease in a tapered, sloped, or stepped manner in the distal direction. In yet another example, the height of the bristles 46 may increase or decrease in an undulating pattern along the length of the tissue collection device 12. These are just a few examples. The height of the bristles 46 may be arranged in any desired configuration.

[0038] Once the tissue collection device 12 is deployed from the outer tubular member 14, the second handle 30 can be actuated to repeatedly advance, retract, and / or rotate the tissue collection device 12 distally and proximally along the target collection site, causing the bristles 46 to brush against the tissue surface and capture cells therebetween. Once the clinician has captured cells from the target site, the inner tubular member 16 can be retracted proximally until the tissue collection device 12 is positioned within the lumen 18 of the outer tubular member 14 and the atraumatic distal tip member 32 contacts the distal end of the outer tubular member 14, sealing the distal opening of the outer tubular member 14. Sealing the distal opening of the outer tubular member 14 can prevent the collection sample from being lost when the tissue collection system 10 is removed from the body.

[0039] Figure 3 is a cross-sectional view of the distal end region 102 of another exemplary tissue collection device system 100 having a removable tissue collection device 120. In Figure 3, the tissue collection device 120 is shown separated or detached from the inner tubular member 106. However, it should be understood that the tissue collection device 120 is coupled to the inner tubular member 106 during delivery of the system 100 and during sample collection.

[0040] The tissue sampling system 100 may include an outer or external elongate shaft or tubular member 104 and an inner elongate shaft or tubular member 106. The inner tubular member 106 may be slidably disposed within a lumen 108 of the outer tubular member 104. The outer tubular member 104 may extend proximally from a distal end region 110 to a proximal end region (not shown) configured to remain outside the patient's body. Although not shown, a first hub or handle similar in form and function to the first handle 24 of FIGS. 1 and 2 may be coupled to the proximal end region of the outer tubular member 104. The inner tubular member 106 may extend proximally from a distal end region 112 to a proximal end region (not shown) configured to remain outside the patient's body. A second hub or handle similar in form and function to the second handle 30 of FIGS. 1 and 2 may be coupled to the proximal end region of the inner tubular member 106.

[0041] The outer tubular member 104 may include a lumen 108 extending from the distal end region 110 to the proximal end region. The lumen 108 may also extend through the first handle. The lumen 108 of the outer tubular member 104 and the first handle may be configured to slidably receive the inner tubular member 106. The inner tubular member 106 may include a lumen 114 extending from the distal end region 112 to the proximal end region. The lumen 114 of the inner tubular member 106 may also extend through the second handle. The lumen 114 of the inner tubular member 106 may be configured to receive a guidewire (not explicitly shown), if desired.

[0042] The distal end region 112 of the inner tubular member 106 may include a coupling mechanism 116 configured to removably secure the inner tubular member 106 to the tissue collection device 120. In the illustrated embodiment, the coupling mechanism 116 may include a plurality of external threads 118 formed on the outer surface of the inner tubular member 106. The external threads 118 may be configured to mate with corresponding threads 128 on the tissue collection device 120. It is envisioned that other removable coupling mechanisms may be used, such as, but not limited to, a friction fit, a snap fit (e.g., but not limited to, a mating detent and groove), a bayonet-style coupling mechanism, a quick-release coupling mechanism, a spring-loaded hook, etc., as desired.

[0043] The tissue harvesting device 120 may include an elongate shaft 150 extending from a distal end region 122 to a proximal end region 124. The tissue harvesting device 120 may include a lumen 140 extending from the distal end region 122 to the proximal end region 124. When the tissue harvesting device 120 is coupled to the inner tubular member 106, the lumen 140 may be in communication with the lumen 114 of the inner tubular member. The lumen 140 of the tissue harvesting device 120 may be configured to receive a guidewire, if desired.

[0044] The proximal end region 124 of the tissue collection device 120 may include a coupling mechanism 126 configured to be removably secured to the coupling mechanism 116 of the inner tubular member 106. The coupling mechanism 126 may include a plurality of internal threads 128 configured to mate with corresponding threads 118 on the inner tubular member 106. It is envisioned that the thread configuration may be reversed, such that the internal threads are disposed on the inner tubular member 106 and the external threads are disposed on the tissue collection device 120. It is envisioned that other removable coupling mechanisms may be used, such as, but not limited to, a friction fit, a snap fit (e.g., but not limited to, a mating detent and groove), a bayonet-style coupling mechanism, a quick-release coupling mechanism, a spring-loaded hook, or the like, as desired. The coupling mechanism 126 of the tissue collection device 120 may include a radially extending gasket or sealing mechanism 152 proximal to the plurality of bristles 142. The sealing mechanism 152 may have an outer diameter sized to allow the tissue collection 120 to slide within the lumen of the outer tubular member 104 while substantially blocking fluid flow through the lumen 108. For example, the outer diameter of the sealing mechanism 152 may be about the same as or smaller than the inner diameter of the outer tubular member 104. It is contemplated that the outer diameter of the sealing mechanism 152 may be larger than the inner diameter of the outer tubular member 104, provided that the inner surfaces of the sealing mechanism 152 and the outer tubular member 104 are suitably lubricious. Although the sealing mechanism 152 is described as extending from the coupling mechanism 126, it is contemplated that the sealing mechanism 152 may extend from the elongate shaft 150, if desired.

[0045] The distal end region 122 of the tissue harvesting device 120 may include an atraumatic distal tip member 130. The atraumatic distal tip member 130 may include a body 132 having a proximal end 134, a distal end 136, and an intermediate region 138. The body 132 may be solid, and the lumen 140 of the tissue harvesting device 120 extends through the body 132. The cross-sectional dimension of the atraumatic distal tip member 130 in a direction generally perpendicular to the longitudinal axis of the tissue harvesting device 120 may vary along the length of the atraumatic distal tip member 130. For example, the cross-sectional dimension may increase distally from the proximal end 134 toward the intermediate region 138 and decrease from the intermediate region 138 toward the distal end 136. Stated another way, the maximum cross-sectional dimension of the atraumatic distal tip member 130 may be at or near the intermediate region 138. It is envisioned that such a configuration allows the proximal end 134 of the atraumatic distal tip member 130 to be disposed within the lumen 108 of the outer tubular member 104 during delivery and removal of the device. The intermediate region 138 may have a cross-sectional dimension similar to or greater than the inner diameter of the outer tubular member 104 such that the intermediate region 138 may abut, contact, or abut the distal end region 110 of the outer tubular member 104 and seal the lumen 108 of the outer tubular member 104. This may help reduce sample loss during retraction of the system 100, as described in more detail herein.

[0046] In some embodiments, the tissue collection device 120 may include a brush mechanism including a plurality of bristles 142. While the tissue collection device 120 is described as a brush mechanism, it is contemplated that other tissue collection devices may be used as desired. The bristles 142 may extend radially outward from the outer surface of the elongate shaft 150. The bristles 142 may be arranged in a first brush cluster 144a, a second brush cluster 144b, and a third brush cluster 144c (collectively 144). While the tissue collection device 120 is shown as including three longitudinally spaced brush clusters 144, the tissue collection device 120 may include fewer than three (e.g., one or two) or more than three (e.g., four, five, six, or more) brush clusters 144. The bristles 142 may be bonded, glued, or otherwise secured to the outer surface of the inner tubular member 106. In some cases, the bristles 142 may be directly bonded to the outer surface of the inner tubular member 106. Alternatively, the bristles 142 may be secured to one or more collars or rings, which are in turn bonded to the outer surface of the inner tubular member 106. It is envisioned that the collars or rings may be solid components or may comprise multiple wires twisted together into a cylindrical tube, in which case the bristles 142 may be clamped between the multiple twisted wires.

[0047] The first brush cluster 144a and the third brush cluster 144c have a first height, and the second brush cluster 144b has a second height that is greater than the first height. It is contemplated that other height combinations of bristles 142 or brush clusters 144 may be used as desired. For example, the height of the bristles 142 may increase in a tapered, sloped, or stepped manner in the distal direction. Alternatively, the height of the bristles 142 may decrease in a tapered, sloped, or stepped manner in the distal direction. In yet another example, the height of the bristles 142 may increase or decrease in an undulating pattern along the length of the tissue collection device 120. These are just a few examples. The height of the bristles 142 may be arranged in any desired configuration.

[0048] The bristles 142 may be employed to brush against a tissue surface within a target area to capture cells. The bristles 142 may be disposed / mounted around an intermediate region of the elongate shaft 150. In some embodiments, each of the bristles 142 may have a substantially circular cross-section. However, the bristles 142 may have any other suitable cross-sectional shape, including rectangular, triangular, square, polygonal, elliptical, or oval.

[0049] The bristles 142 may be made of one or more filaments. For example, the multiple bristles 142 may be made of a continuous length of filament. Alternatively, the multiple bristles 142 may be made of discrete lengths of filament. The filament may be a monofilament. The monofilament may be formed by extrusion. Alternatively, the filament may be a multicomponent filament. A multicomponent filament may include a core with one or more layers of material concentrically arranged. If multiple layers are present, they may differ in composition and / or thickness. The outermost layer may include micropatterning, as described in more detail below. A multicomponent filament may be formed by coextrusion. It is contemplated that the filament may be made of nylon, polymer, and / or any suitable material or combination of materials.

[0050] It is contemplated that the bristles 142 may be arranged in any desired configuration. In some cases, the bristles 142 may be arranged helically around the distal portion of the inner tubular member 106 or may extend radially outward from the inner tubular member. In some embodiments, the bristles 142 may radiate at an angle relative to the longitudinal axis of the inner tubular member 106. It is further contemplated that the density of the bristles 142 may vary along the length of the tissue collection device 120 or between clusters 144 a, 144 b, 144 c. In some cases, the length of the bristles 142 may vary. As the bristles 142 are rubbed against tissue in the target area, cells from the tissue may migrate to the bristles 142 and become trapped between the bristles 142.

[0051] In some embodiments, the inner tubular member 106 and the tissue collection device 120 may be formed of the same material. In other embodiments, the inner tubular member 106 and the tissue collection device 120 may be formed of different materials. For example, the tissue collection device 120 may be formed of a material that facilitates the attachment, bonding, or formation of the bristles 142.

[0052] When the tissue collection device 120 is disposed within the outer tubular member 104, the tissue collection device 120 may be constrained in a reduced-diameter, compressed or delivery configuration by the outer tubular member 104 surrounding the tissue collection device 120. In the compressed configuration (not explicitly shown), the tissue collection device 120 may have a smaller diameter than in the expanded, deployed configuration. The distal end region 110 of the outer tubular member 104 may be positioned such that the outer tubular member 104 surrounds and wraps the length of the tissue collection device 120 during delivery. The outer tubular member 104 may have sufficient hoop strength to hold the tissue collection device 120 in its reduced-diameter state.

[0053] The tissue collection system 100 can be advanced through the body toward the target site as desired. It should be understood that during delivery of the system 100 and during sample collection, the tissue collection device 120 is coupled to the inner tubular member 106. The tissue collection system 100 can be advanced with or without the use of a guidewire. Once the tissue collection device 120 is positioned adjacent the target area, the restraining forces maintaining the tissue collection device 120 in a radially compressed configuration are removed, and the tissue collection device 120 can be deployed.

[0054] The tissue collection device 120 can be deployed by actuating the second handle, e.g., by pushing the second handle distally, while maintaining the first handle in a fixed position. Thus, the inner tubular member 106 can be advanced distally relative to the outer tubular member 104. In other words, the inner tubular member 106 can be advanced distally while the outer tubular member 104 remains stationary. The reverse configuration is also contemplated. For example, the outer tubular member 104 can be retracted proximally while the inner tubular member 106 remains stationary. When the inner tubular member 106 is advanced distally, the biasing force is removed from outside the tissue collection device 120, and the tissue collection device 120 assumes its radially expanded, unbiased, deployed configuration.

[0055] Once the tissue collection device 120 is deployed from the outer tubular member 104, the second handle can be actuated to repeatedly advance, retract, and / or rotate the tissue collection device 120 distally along the target collection site, causing the bristles 142 to brush against the tissue surface and capture cells between the bristles 142. Once the clinician has captured cells from the target site, the inner tubular member 106 can be retracted proximally until the tissue collection device 120 is positioned within the lumen 108 of the outer tubular member 104 and the atraumatic distal tip member 130 contacts the distal end of the outer tubular member 104. The sealing mechanism 152 can engage the inner wall of the outer tubular member 104, and the distal tip member 130 can seal the distal opening of the outer tubular member 104. Sealing the proximal end region 124 of the tissue collection device 120 and the distal opening of the outer tubular member 104 can prevent the collected sample from dissipating (e.g., into the space between the inner tubular member 106 and the outer tubular member 104) during removal of the tissue collection system 100 from the endoscope and / or body.

[0056] FIG. 5 is an exemplary flowchart of a method 200 for obtaining a tissue sample using the system 10, 100 of FIGS. 1-3. First, as shown in block 210, the tissue collection system 10, 100 can be advanced to a target site within the body. In some embodiments, the tissue collection system 10, 100 can be advanced through an endoscope and its distal end can be positioned near the target site. For example, to obtain a sample from the common bile duct, the endoscope can be advanced through the esophagus, through the stomach, and into the duodenum. The tissue collection system 10, 100 can be positioned within the endoscope while the endoscope is in position, or can be advanced through the endoscope thereafter. Next, the guidewire 42 of the tissue collection system 10, 100 can be advanced distally to cannulate the common bile duct. Next, as shown in block 220, the inner tubular member 16, 106 can be advanced distally over the guidewire to deploy the tissue collection device 12, 120. As described above, the inner tubular member 16, 106 can be advanced distally while the outer tubular member 14, 104 remains stationary so that the tissue collection device 12, 120 exits the outer tubular member 14, 104. Because the guidewire 42 is centrally located within the tissue collection system 10, 100, it is envisioned that the inner tubular member 16, 106 will not become biased to one side, as is the case with tissue collection systems that advance a brush through a channel separate from the guidewire. The coaxial arrangement of the guidewire 42 and inner tubular member 16, 106 allows the atraumatic distal tip member 32, 130 and tissue collection device to easily pass through ampullae, bends, and strictures.

[0057] Once the tissue collection device 12, 120 is positioned at the target site, the inner tubular member 16, 106 can be actuated (e.g., using the second handle 30) back and forth (e.g., proximally and distally) to drag the bristles 46, 142 along the collection site and collect cells, as shown in block 230. In some cases, the inner tubular member 16, 106 can be rotated in addition to or instead of proximal and distal movement. Once the sample has been collected, the inner tubular member 16, 106 can be retracted proximally to pull the tissue collection device 12, 120 back into the lumen 108 of the outer tubular member 14, 104, as shown in block 240. The inner tubular member 16, 106 can be retracted until the atraumatic distal tip member 32, 130 contacts the distal end of the outer tubular member 14, 104. As described above, the atraumatic distal tip member 32, 130 may help block or close the distal opening of the outer tubular member 14, 104, reducing sample loss during removal of the tissue collection system 10, 100 from the body. If so provided, the sealing mechanism 152 may form a proximal seal to further reduce sample loss. Once the atraumatic distal tip member 32, 130 is positioned against the distal end of the outer tubular member 14, 104, the tissue collection system 10, 100 may be removed from the body, as shown in block 250.

[0058] Next, as shown in block 260, the inner tubular member 16 may be cut (e.g., using wire cutters or other cutting device) at a location proximal to the tissue collection device 12 so that the tissue collection device 12 may be placed into a sample container. Alternatively, the tissue collection device 120 may be separated from the inner tubular member 106 by actuating the coupling mechanisms 116, 126. If another sample is desired, it is envisioned that another tissue collection device 120 may be coupled to the coupling mechanism 116 of a previously used inner tubular member 106. This may help reduce costs and waste by allowing multiple cytology passes to be performed using two or more tissue collection devices 120 while still using a single tissue collection system. Because the tissue collection device 120 is removed (e.g., unscrewed in the illustrated example) from the inner tubular member 106 by actuating the coupling mechanisms 116, 126, this may also simplify the process of cutting the tissue collection device using wire cutters for placement into a sample container. Instead, the tissue sampling system 10 of Figures 1 and 2 requires that an entirely new inner tubular member 16 assembly and tissue sampling device 12 be used for each desired sample.

[0059] The various components of the medical device system 10, 100 (and / or other systems disclosed herein) and materials that may be used for the various elements thereof disclosed herein may include those commonly associated with medical devices. For simplicity, the following discussion will refer to the tissue harvesting system 10, 100 and / or tissue harvesting device 12, 120. However, this is not intended to limit the devices and methods described herein, and the discussion may apply to other elements, members, components, or devices disclosed herein, such as, but not limited to, the inner tubular member 16, 106 and outer tubular member 14, 104, the handles 24, 30, the guidewire 42, the distal tip member 32, 130, etc., and / or elements or components thereof.

[0060] In some embodiments, the tissue harvesting system 10, 100, tissue harvesting device 12, 120, and / or components thereof may be made from metals, metal alloys, polymers (some examples of which are disclosed below), metal-polymer composites, ceramics, combinations thereof, and the like, or other suitable materials.

[0061] Some examples of suitable polymers include polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), polyoxymethylene (POM, e.g., DELRIN® available from DuPont), polyether block esters, polyurethanes (e.g., Polyurethane 85A), polypropylene (PP), polyvinyl chloride (PVC), polyetheresters (e.g., ARNITEL® available from DSM Engineering Plastics), ether or ester-based copolymers (e.g., butylene / poly(alkylene ether) phthalates and / or other polyester elastomers such as HYTREL® available from DuPont), polyamides (e.g., DURETHAN® or Elf® available from Bayer), and the like. CRISTAMID® available from Atochem), elastomeric polyamides, block polyamide / ethers, polyether block amides (PEBA, e.g., available under the trade name PEBAX®), ethylene vinyl acetate copolymer (EVA), silicone, polyethylene (PE), Marlex high density polyethylene, Marlex low density polyethylene, linear low density polyethylene (e.g., REXELL®), polyester, polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polytrimethylene terephthalate, polyethylene naphthalate (PEN), polyether ether ketone (PEEK), polyimide (PI), polyetherimide (PEI), polyphenylene sulfide (PPS), polyphenylene oxide (PPO), polyparaphenylene terephthalamide (e.g., KEVLAR®), polysulfone, nylon, nylon-12 (e.g., EMS American GRILAMID® available from Grillon), perfluoro(propyl vinyl ether) (PFA), ethylene vinyl alcohol, polyolefins, polystyrene, epoxies, polyvinylidene chloride (PVdC), poly(styrene-b-isobutylene-b-styrene) (e.g., SIBS and / or SIBS50A), polycarbonates, ionomers, biocompatible polymers, other suitable materials, or mixtures, combinations, copolymers, polymer / metal composites, and the like.

[0062] Some examples of suitable metals and alloys include stainless steels such as 304V, 304L, and 316LV stainless steel, mild steel, nickel-titanium alloys such as linear elastic and / or superelastic nitinol, other nickel alloys such as nickel-chromium-molybdenum alloys (e.g., UNS: N06625 such as INCONEL® 625, UNS: N06022 such as HASTELLOY® C-22®, HASTELLOY® C276®, and the like). and other HASTELLOY® alloys), nickel-copper alloys (e.g., UNS:N04400 such as MONEL® 400, NICKELVAC® 400, and NICORROS® 400), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS:R30035 such as MP35-N®), nickel-molybdenum alloys (e.g., HASTELLOY® ALLOY®), B2®), other nickel-chromium alloys, other nickel-molybdenum alloys, other nickel-cobalt alloys, other nickel-iron alloys, other nickel-copper alloys, and other nickel-tungsten or tungsten alloys, cobalt-chromium alloys, cobalt-chromium-molybdenum alloys (e.g., UNS:R30003, such as ELGILOY® and PHYNOX®), platinum strengthened stainless steel, titanium, and combinations thereof, or any other suitable material.

[0063] As mentioned herein, within the family of commercially available nickel-titanium or nitinol alloys, there is a category referred to as “linear elastic” or “non-superelastic,” which may be chemically similar to traditional shape memory and superelastic varieties but may exhibit distinct and useful mechanical properties. Linear elastic and / or non-superelastic nitinol may be distinguished from superelastic nitinol in that linear elastic and / or non-superelastic nitinol does not exhibit a substantial “superelastic plateau” or “flag region” in its stress / strain curve as does superelastic nitinol. Instead, in linear elastic and / or non-superelastic nitinol, as recoverable strain increases, stress continues to increase in a substantially linear manner until plastic deformation begins, or in a relationship that is somewhat linear but not necessarily entirely linear, or at least more linear than the superelastic plateau and / or flag region that may be seen in superelastic nitinol. Thus, for purposes of this disclosure, linear elastic and / or non-superelastic nitinol may also be referred to as “substantially” linear elastic and / or non-superelastic nitinol.

[0064] In some cases, linear elastic and / or non-superelastic nitinol can also be distinguished from superelastic nitinol in that linear elastic and / or non-superelastic nitinol can accommodate a maximum of about 2 to 5% strain while remaining substantially elastic (e.g., before plastic deformation), while superelastic nitinol can accommodate a maximum of about 8% strain before plastic deformation. Both of these materials can be distinguished from other linear elastic materials, such as stainless steel (which can also be distinguished based on its composition), which can accommodate only about 0.2 to 0.44 percent strain before plastic deformation.

[0065] In some embodiments, linear elastic and / or non-superelastic nickel-titanium alloys are alloys that do not exhibit a martensite / austenite phase change detectable by differential scanning calorimetry (DSC) and dynamic metal thermal analysis (DMTA) analysis over a wide temperature range. For example, in some embodiments, linear elastic and / or non-superelastic nickel-titanium alloys may not exhibit a martensite / austenite phase change detectable by DSC and DMTA analysis over a range of about -60 degrees Celsius (°C) to about 120°C. Thus, the mechanical bending properties of such materials may generally be inert to the effects of temperature over this very wide temperature range. In some embodiments, the mechanical bending properties of linear elastic and / or non-superelastic nickel-titanium alloys at ambient or room temperature are substantially the same as those at body temperature, e.g., in that they do not exhibit a superelastic plateau and / or flag region. In other words, over a wide temperature range, linear elastic and / or non-superelastic nickel-titanium alloys maintain their linear elastic and / or non-superelastic characteristics and / or properties.

[0066] In some embodiments, the linear elastic and / or non-superelastic nickel-titanium alloy may range from about 50 to about 60 weight percent nickel, with the remainder essentially titanium. In some embodiments, the composition may range from about 54 to about 57 weight percent nickel. One example of a suitable nickel-titanium alloy is FHP-NT alloy, commercially available from Furukawa Techno Material Co., Ltd., Kanagawa Prefecture, Japan. Other suitable materials may include ULTANIUM™ (available from Neo-Metrics) and GUM METAL™ (available from Toyota). In some other embodiments, a superelastic alloy, such as superelastic nitinol, may be used to achieve desired properties.

[0067] In at least some embodiments, the tissue collection system 10, 100, tissue collection device 12, 120, and / or some or all of their components may also be doped with, made from, or otherwise include a radiopaque material. A radiopaque material is understood to be a material capable of producing a relatively bright image on a fluoroscopy screen or another imaging technique during a medical procedure. This relatively bright image aids the user of the medical device system 10 in determining its location. Some examples of radiopaque materials may include, but are not limited to, gold, platinum, palladium, tantalum, tungsten alloys, polymeric materials filled with radiopaque fillers, and the like. Additionally, other radiopaque marker bands and / or coils may be incorporated into the design of the medical device system 10 to achieve the same results.

[0068] In some embodiments, a degree of magnetic resonance imaging (MRI) compatibility is imparted to the medical device system 10. For example, the tissue collection system 10, 100, tissue collection device 12, 120, and / or components or portions thereof may be made of materials that do not substantially distort images or produce substantial artifacts (e.g., gaps in images). For example, certain ferromagnetic materials may not be suitable because they may produce artifacts in MRI images. The tissue collection system 10, 100, tissue collection device 12, 120, or portions thereof, may also be made of materials that can be imaged by MRI machines. Some materials that exhibit these properties include, for example, tungsten, cobalt-chromium-molybdenum alloys (e.g., UNS:R30003, such as ELGILOY® and PHYNOX®), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS:R30035, such as MP35-N®), nitinol, and the like, among others.

[0069] In some embodiments, the exterior surfaces of the medical device system 10 (including, for example, the exterior surfaces of the delivery system) may be treated with sandblasting, bead blasting, sodium bicarbonate blasting, electropolishing, or the like. In these and some other embodiments, a coating, such as a lubricious, hydrophilic, protective, or other type of coating, may be applied over a portion or all of the outer sheath, or, in embodiments without an outer sheath, over a portion of the delivery system or other portions of the medical device system 10. Hydrophobic coatings, such as fluoropolymers, provide dry lubricity to improve device handling and device exchange. Lubricious coatings improve steerability and lesion crossing capabilities. Suitable lubricious polymers are well known in the art and may include hydrophilic polymers such as silicones (e.g., high-density polyethylene (HDPE), polytetrafluoroethylene (PTFE), polyarylene oxides, polyvinylpyrrolidone, polyvinyl alcohol, hydroxyalkyl cellulose, algin, saccharides, caprolactone, etc.), and mixtures and combinations thereof. Hydrophilic polymers can be blended among themselves or with amounts of water-insoluble compounds (including some polymers) to obtain coatings with suitable lubricity, binding, and solubility properties.

[0070] The coating and / or sheath can be formed, for example, by coating, extrusion, coextrusion, interrupted layer coextrusion (ILC), or by fusing several segments end-to-end. The layers can have uniform or tapered stiffness from their proximal to distal ends. The tapered stiffness can be continuous, as with ILC, or gradual, as with fusing separate extruded tubular segments together. The outer layer can be impregnated with a radiopaque filler material to facilitate radiographic visualization. Those skilled in the art will recognize that these materials can vary widely without departing from the scope of the present invention.

[0071] It is to be understood that the present disclosure is in many respects merely illustrative. Changes may be made in details, particularly in matters of shape, size, and arrangement of steps, without departing from the scope of the invention. This may include, to the extent appropriate, the use of any of the features of one illustrative embodiment used in another embodiment. The scope of the invention is, of course, defined in the language in which the appended claims are expressed.

Claims

1. 1. A tissue sampling system comprising: an outer tubular member having a proximal end region and a distal end region and defining a lumen extending from the proximal end region to the distal end region; an inner tubular member slidably disposed within the lumen of the outer tubular member, the inner tubular member defining a lumen extending from a proximal end region to a distal end region of the inner tubular member, the distal end region including an atraumatic distal tip member sized and shaped to facilitate advancement of the tissue sampling system; a tissue sampling device disposed adjacent the distal end region of the inner tubular member; the inner tubular member is movable between a retracted delivery position and an advanced sample collection position; the atraumatic distal tip member includes a body having a proximal end, a distal end, and an intermediate region; a cross-sectional dimension of the atraumatic distal tip member varies along its length such that a maximum cross-sectional dimension of the atraumatic distal tip member is located at the intermediate region, the cross-sectional dimension increasing in a distal direction from the proximal end toward the intermediate region, and the cross-sectional dimension decreasing in a distal direction from the intermediate region toward the distal end; the maximum cross-sectional dimension at the intermediate region is greater than the inner diameter of the outer tubular member such that the distal end region of the outer tubular member abuts the intermediate region of the atraumatic distal tip member in the retracted delivery position.

2. The tissue sampling system of claim 1 , wherein the tissue sampling device is disposed about the outer surface of the inner tubular member.

3. The tissue sampling system of claim 1 , wherein the tissue sampling device is removably coupled to the distal end region of the inner tubular member.

4. The tissue sampling system of claim 3 , wherein the distal end region of the inner tubular member comprises a coupling mechanism.

5. The tissue sampling system of claim 4 , wherein the coupling mechanism of the inner tubular member comprises a plurality of threads.

6. The tissue harvesting system of claim 3 , wherein the tissue harvesting device comprises an elongate shaft extending from a distal end region to a proximal end region and defining a lumen extending from the distal end region to the proximal end region.

7. The tissue harvesting system of claim 6 , wherein the proximal end region of the tissue harvesting device comprises a coupling mechanism.

8. The tissue harvesting system of claim 7 , wherein the coupling mechanism of the tissue harvesting device comprises a plurality of threads.

9. The tissue sampling system of claim 7 , wherein the coupling mechanism of the tissue sampling device is configured to be removably coupled to the coupling mechanism of the inner tubular member.

10. The tissue sampling system of claim 6 , wherein the tissue sampling device further comprises a radially extending sealing mechanism positioned adjacent the proximal end region of the tissue sampling device.

11. The tissue sampling system of claim 1 , wherein the tissue sampling device includes a brush mechanism.

12. The tissue sampling system of claim 11 , wherein the brush mechanism comprises a plurality of radially extending bristles.

13. The tissue collection system of claim 12, wherein the length of the bristles varies and / or the density of the bristles varies along the length of the tissue collection device.

14. 14. The tissue sampling system of claim 1, further comprising a guidewire, the guidewire being coaxially disposed with the inner tubular member and configured to be slidably disposed within the lumen of the inner tubular member.

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