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 DISCLOSURE 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 of cells from a target area of ​​a subject's body. For example, a screening test to detect potential pre-cancerous and cancerous tissues in a subject's body may include taking a tissue or cell sample from a target area of ​​a subject's body. A tissue harvesting device can be used to harvest cells or other tissues from the target area. Tissue harvesting 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, materials, manufacturing methods, and use alternatives for medical devices. In a first embodiment, a 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 may be 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, a 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 sampling 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 coupling mechanism. Alternatively or in addition 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 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.

[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 coupling mechanism. Alternatively or in addition to any of the above examples, in another example, the attachment 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 sampling device may 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 and radially extending from a 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 in addition 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 radially extending bristles may be grouped into brush clusters. Alternatively, or in addition to any of the above examples, in another example, the tissue sampling 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 sampling 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 sampling device disposed about and extending radially therefrom 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 sampling 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 sampling 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 sampling 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 sampling 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 coupling mechanism. Alternatively, or in addition to any of the above examples, in another example, the coupling mechanism of the tissue sampling device may 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 description of the drawings]

[0019] The present invention may be more fully understood from the following detailed description of various embodiments considered in conjunction with the accompanying drawings. [Figure 1] 1A-1D 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. [Diagram 2]2 illustrates a partial cross-sectional side view of the exemplary tissue sampling device system shown in FIG. 1 with the tissue sampling device in a deployed or sampling configuration. [Diagram 3] 1 illustrates a cross-sectional view of a distal end region of another exemplary tissue harvesting device delivery system. [Figure 4] 4 is an exemplary flow chart 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, details 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 PREFERRED EMBODIMENTS

[0021] All numerical values, whether expressly indicated 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 cases, 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 illustrated exemplary embodiments are intended as examples only. Selected features of the exemplary embodiments may be incorporated in 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 being treated today is strictures in the CBD due to, but not limited to, primary sclerosing cholangitis (PSC), cholangiocarcinoma, gallstone damage and scarring within the bile duct. ERCP has now matured primarily as an interventional procedure. When clinicians need to take a sample of the stricture, 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 is often still problematic. The tip of the mechanism often does not pass through the ampulla and / or stricture. Current tissue sampling devices or brushes may include devices with snub-nose outer catheter tips. The guidewire may be advanced through a separate channel in the catheter adjacent to the brush, rather than inside the brush. As a result, upon insertion, the tip of the catheter has difficulty passing through curved surfaces and strictures and tends to impinge on the outer surface of the bend. Tissue sampling devices and systems that allow the tip of the delivery catheter and the tissue sampling device to easily pass through ampulla, bends, and strictures may be desirable. Although 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 include, but are 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 cross-sectional side view of an exemplary tissue harvesting device system 10 for delivering a tissue harvesting device 12 to a target area, such as, but not limited to, the common bile duct or pancreatic duct, in a retracted or delivery configuration. The tissue harvesting 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 that is 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 harvesting 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 along the distal direction 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 about a portion of the inner tubular member 16 at or adjacent to the distal end region 26 of the inner tubular member 16. The tissue collection device 12 may extend about the entire circumference of the inner tubular member 16. In other embodiments, the tissue collection device 12 may be radially spaced about 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. Although the tissue collection device 12 is described as a brush mechanism, it is envisioned 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 disposed in a first brush cluster 44a, a second brush cluster 44b, and a third brush cluster 44c (collectively 44). Although the tissue sampling device 12 is shown as including three longitudinally spaced apart brush clusters 44, the tissue sampling device 12 may include less 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. 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 46 may be clamped between the multiple twisted wires.

[0031] The bristles 46 may be employed to brush against a tissue surface in the 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, the bristles 46 may each 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. The multicomponent filament may be formed by coextrusion. It is envisioned 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 and 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 harvesting device 12 or between the clusters 44a, 44b, 44c. In some cases, the length of the bristles 46 may vary. When the bristles 46 are rubbed against the tissue of the target area, cells from the tissue may be transferred to the bristles 46 and trapped between the bristles 46.

[0034] When the tissue harvesting device 12 is disposed within the outer tubular member 14, the tissue harvesting device 12 may be constrained in a reduced diameter, compressed or delivery configuration by the outer tubular member 14 surrounding the tissue harvesting device 12. In the compressed configuration, the tissue harvesting 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 harvesting device 12 during delivery. The outer tubular member 14 may have sufficient hoop strength to hold the tissue harvesting device 12 in its reduced diameter state.

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

[0036] The tissue harvesting device 12 may be deployed by actuating the second handle 30, for example by pushing the second handle 30 distally, while maintaining the first handle 24 in a fixed position. Thus, the inner tubular member 16 may be advanced distally relative to the outer tubular member 14. In other words, the inner tubular member 16 may be advanced distally while the outer tubular member 14 is stationary. The reverse configuration is also contemplated. For example, the outer tubular member 14 may 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 harvesting device 12 and the tissue harvesting 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 can be used as desired. For example, the height of the bristles 46 can increase in a tapered, sloping, or stepped manner in the distal direction. Alternatively, the height of the bristles 46 can decrease in a tapered, sloping, or stepped manner in the distal direction. In yet another example, the height of the bristles 46 can increase or decrease in an undulating pattern along the length of the tissue sampling device 12. These are just a few examples. The height of the bristles 46 can 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 distally, retract proximally, and / or rotate the tissue collection device 12 along the target collection site, causing the bristles 46 to brush against the tissue surface and capture cells between the bristles 46. 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 disposed 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 and may seal the distal opening of the outer tubular member 14. Sealing the distal opening of the outer tubular member 14 may 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 sampling device system 100 having a removable tissue sampling device 120. In Figure 3, the tissue sampling device 120 is shown separated or detached from the inner tubular member 106. However, it should be understood that the tissue sampling 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 a distal end region 110 to a 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 harvesting device 120. In the illustrated embodiment, the coupling mechanism 116 may include a plurality of external threads 118 formed on an outer surface of the inner tubular member 106. The external threads 118 may be configured to mate with corresponding threads 128 on the tissue harvesting device 120. It is envisioned that other removable coupling mechanisms may be used as desired, 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, and the like.

[0043] The tissue harvesting device 120 may include an elongate shaft 150 extending from the distal end region 122 to the 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 harvesting 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 female 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 female threads are disposed on the inner tubular member 106 and the male threads are disposed on the tissue harvesting device 120. It is envisioned that other removable coupling mechanisms may be used as desired, such as, but not limited to, friction fit, snap fit (e.g., but not limited to, mating detent and groove), bayonet-type coupling mechanisms, quick release coupling mechanisms, spring-loaded hooks, and the like. The coupling mechanism 126 of the tissue harvesting device 120 may include a radially extending gasket or seal 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 sampling device 120 may include a brush mechanism including a plurality of bristles 142. Although the tissue sampling device 120 is described as a brush mechanism, it is envisioned that other tissue sampling 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). Although the tissue sampling device 120 is shown as including three longitudinally spaced apart brush clusters 144, the tissue sampling device 120 may include less 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, adhered, 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 exterior 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 exterior 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, sloping, or stepped manner in the distal direction. Alternatively, the height of the bristles 142 may decrease in a tapered, sloping, 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 sampling 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 in a target area to capture cells. The bristles 142 may be disposed / mounted about 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. The multicomponent filament may be formed by coextrusion. It is envisioned 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 and 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 harvesting device 120 or between the clusters 144a, 144b, 144c. In some cases, the length of the bristles 142 may vary. As the bristles 142 are rubbed against the tissue of the target area, cells from the tissue may be transferred to the bristles 142 and trapped between the bristles 142.

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

[0052] When the tissue harvesting device 120 is disposed within the outer tubular member 104, the tissue harvesting device 120 may be constrained in a reduced diameter compressed or delivery configuration by the outer tubular member 104 surrounding the tissue harvesting device 120. In the compressed configuration (not explicitly shown), the tissue harvesting 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 harvesting device 120 during delivery. The outer tubular member 104 may have sufficient hoop strength to hold the tissue harvesting device 120 in its reduced diameter state.

[0053] The tissue collection system 100 may 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 may 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 may be deployed.

[0054] The tissue harvesting device 120 may be deployed by actuating the second handle, for example by pushing the second handle distally, while maintaining the first handle in a fixed position. Thus, the inner tubular member 106 may be advanced distally relative to the outer tubular member 104. In other words, the inner tubular member 106 may be advanced distally while the outer tubular member 104 is stationary. The reverse configuration is also contemplated. For example, the outer tubular member 104 may be retracted proximally while the inner tubular member 106 is stationary. When the inner tubular member 106 is advanced distally, the biasing force is removed from the outside of the tissue harvesting device 120, and the tissue harvesting 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 distally, retract proximally, and / or rotate the tissue collection device 120 along the target collection site, causing the bristles 142 to brush 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 disposed 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 seal 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 sampling 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 sampling system 100 from the endoscope and / or body.

[0056] FIG. 5 is an exemplary flow chart of a method 200 for obtaining a tissue sample using the system 10, 100 of FIGS. 1-3. First, the tissue collection system 10, 100 may be advanced to a target site within the body, as shown in block 210. In some embodiments, the tissue collection system 10, 100 may be advanced through an endoscope and its distal end may be positioned proximate the target site. For example, to obtain a sample from the common bile duct, the endoscope may be advanced through the esophagus, through the stomach, and into the duodenum. The tissue collection system 10, 100 may be positioned within the endoscope as the endoscope is positioned, or may be advanced through the endoscope thereafter. The guidewire 42 of the tissue collection system 10, 100 may then be advanced distally to cannulate the common bile duct. The inner tubular member 16, 106 may then be advanced distally over the guidewire to deploy the tissue collection device 12, 120, as shown in block 220. As discussed above, the inner tubular member 16, 106 can be advanced distally while the outer tubular member 14, 104 is stationary so that the tissue sampling device 12, 120 exits the outer tubular member 14, 104. Because the guidewire 42 is centrally located within the tissue sampling system 10, 100, it is envisioned that the inner tubular member 16, 106 will not bias to one side, as is the case with tissue sampling 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 sampling device to easily pass through ampullations, bends and strictures.

[0057] Once the tissue harvesting 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 harvesting site and collect the cells, as shown in block 230. In some cases, the inner tubular member 16, 106 can be rotated in addition to or instead of the proximal and distal movement. Once the sample has been harvested, the inner tubular member 16, 106 can be retracted proximally to pull the tissue harvesting 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 mentioned above, the atraumatic distal tip member 32, 130 may serve to block or close the distal opening of the outer tubular member 14, 104 to reduce 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 severed (e.g., using a wire cutter 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. It is envisioned that if another sample is desired, another tissue collection device 120 may be coupled to the coupling mechanism 116 of the previously used inner tubular member 106. This may help reduce costs and waste by allowing multiple cytology passes to be performed using a single tissue collection system but using two or more tissue collection devices 120. 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, it may also simplify the process of using a wire cutter to cut the tissue collection device for placement into a sample container. Instead, with the tissue sampling system 10 of Figures 1 and 2, an entirely new inner tubular member 16 assembly and tissue sampling device 12 must be used for each sample desired.

[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, handles 24, 30, guidewire 42, distal tip member 32, 130, etc., and / or elements or components thereof.

[0060] In some embodiments, the tissue harvesting systems 10, 100, tissue harvesting devices 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. Atochem (CRISTAMID®), elastomeric polyamides, block polyamide / ethers, polyether block amides (PEBA, available, for example, under the trade name PEBAX®), ethylene vinyl acetate copolymers (EVA), silicones, polyethylene (PE), Marlex high density polyethylene, Marlex low density polyethylene, linear low density polyethylene (e.g., REXELL®), polyesters, polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polytrimethylene terephthalate, polyethylene naphthalate (PEN), polyether ether ketone (PEEK), polyimides (PI), polyetherimide (PEI), polyphenylene sulfide (PPS), polyphenylene oxide (PPO), polyparaphenylene terephthalamide (e.g., KEVLAR®), polysulfones, nylons, nylon-12 (e.g., EMS American GRILAMID® available from Grilon), 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 (registered trademark) and other 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®, UNS:N10276, such as HASTELLOY® ALLOY®, UNS:N20001, HASTELLOY® ALLOY®, UNS:N10276, such as HASTELLOY® ALLOY®, UNS:N20002, HASTELLOY® ALLOY®, UNS:N10276, such as HASTELLOY® ALLOY®, UNS:N10276, such as HASTELLOY® ALLOY®, UNS:N10276, such as HASTELLOY® ALLOY®, UNS:N20003, HASTELLOY® ALLOY®, UNS:N10276, such as ... 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" that 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 the recoverable strain increases, the stress continues to increase in a substantially linear or some but not necessarily entirely linear relationship until plastic deformation begins, or at least in a relationship that is 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 may 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), whereas superelastic Nitinol can accommodate a maximum of about 8% strain before plastic deformation. Both of these materials may be distinguished from other linear elastic materials, such as stainless steel (which may 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, the linear elastic and / or non-superelastic nickel-titanium alloy is an alloy that does 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, the linear elastic and / or non-superelastic nickel-titanium alloy may not have a martensite / austenite phase change detectable by DSC and DMTA analysis in the 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 the linear elastic and / or non-superelastic nickel-titanium alloy at ambient or room temperature are substantially the same as the mechanical properties at body temperature, for example, in that they do not exhibit a superelastic plateau and / or flag region. In other words, over a wide temperature range, the linear elastic and / or non-superelastic nickel-titanium alloy maintains its 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, available from Furukawa Techno Materials, Inc., Kanagawa, 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 the desired properties.

[0067] In at least some embodiments, the tissue harvesting system 10, 100, tissue harvesting device 12, 120, and / or some or all of their components may also be doped with, made from, or otherwise include radiopaque materials. A radiopaque material is understood to be a material that can produce 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 also 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 and do not create substantial artifacts (e.g., gaps in the image). For example, certain ferromagnetic materials may not be suitable because they may create 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 MRI machines can image. 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®), and nitinol, 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 sand blasting, bead blasting, sodium bicarbonate blasting, electropolishing, and 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 the entirety 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. A hydrophobic coating, such as a fluoropolymer, provides dry lubricity that improves device handling and device replacement. A lubricious coating improves steerability and improves 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, algins, saccharides, caprolactone, and the like), 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 may be formed, for example, by coating, extrusion, coextrusion, interrupted layer coextrusion (ILC), or by fusing several segments end to end. The layers may have uniform or tapered stiffness from their proximal to distal ends. The tapered stiffness may be continuous, as with ILC, or may be gradual, as with fusing separate extruded tubular segments together. The outer layer may be impregnated with a radiopaque filler material to facilitate visualization by radiography. Those skilled in the art will recognize that these materials may vary widely without departing from the scope of the invention.

[0071] It is to be understood that the present disclosure is in many respects only 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 said proximal end region to said 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; a tissue sampling device disposed adjacent the distal end region of the inner tubular member; A tissue sampling system, wherein the inner tubular member is movable between a retracted delivery position and an advanced sample-collecting position.

2. The tissue sampling system of claim 1 , wherein the tissue sampling device is disposed about an 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 sampling system of any one of claims 3 to 5, wherein the tissue sampling 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 sampling system of claim 6 , wherein the proximal end region of the tissue sampling device comprises a coupling mechanism.

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

9. The tissue sampling system of claim 7 or 8, 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 any one of claims 6 to 9, wherein the tissue sampling device further comprises a sealing mechanism positioned adjacent and extending radially from the proximal end region of the tissue sampling device.

11. The tissue sampling system of any one of claims 1 to 10, further comprising an atraumatic distal tip member disposed distally of the tissue sampling device.

12. The tissue sampling system of claim 11 , wherein at least a portion of the atraumatic distal tip member is configured to contact a distal end of the outer tubular member when the inner tubular member is in a retracted delivery configuration.

13. The tissue sampling system according to any one of claims 1 to 12, wherein the tissue sampling device includes a brush mechanism.

14. The tissue sampling system of claim 13 , wherein the brush mechanism comprises a plurality of radially extending bristles.

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

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