Tissue separator

Abstract

A biopsy device comprising: a hollow sampling portion comprising an elongate body having a major axis, a proximal end, a distal end, and a lumen disposed within the body along the major axis; wherein the sampling portion distal end comprises a distal end opening shaped and sized to allow tissue to enter the lumen when the hollow sampling portion is axially advanced into body tissue; at least one movable tissue manipulator extending from a wall of the sampling portion body into the lumen and toward the proximal end of the sampling portion; wherein the at least one tissue manipulator is configured to move outwardly toward the wall and inwardly toward the lumen.

Description

[0001] Related applications This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 532,930, filed August 16, 2023, the entire contents of which are incorporated herein by reference.

[0002] Field and background of the invention In some embodiments, the present invention relates to tissue sampling, and more specifically, but not exclusively, to soft tissue sampling for biopsy. Summary of the Invention

[0003] The following are some exemplary embodiments of the present invention (the embodiments may include features from more than one example and / or all features from fewer than one example): Example 1. A biopsy device, comprising: a. A hollow sampling portion comprising an elongated body having a long axis, a proximal end, a distal end, and an inner cavity located within the body along the long axis; wherein the distal end of the sampling portion includes a distal opening whose shape and size are designed to allow tissue to enter the inner cavity when the hollow sampling portion is axially advanced into body tissue; b. At least one movable tissue manipulator extending from the wall of the sampling portion body into the cavity and toward the proximal end of the sampling portion; The at least one tissue manipulator is configured to move outward toward the wall and inward toward the lumen.

[0004] Example 2. The apparatus according to Example 1, wherein the at least one movable tissue manipulator is shaped and sized to be pushed by the tissue entering the cavity against the inner surface of the wall of the sampling portion, and to be moved back toward the cavity and to apply force to the tissue in the cavity.

[0005] Example 3. The apparatus according to any one of Examples 1 or 2, wherein the at least one tissue manipulator is configured to move back toward the inner cavity when the axial advance of the hollow sampling portion stops.

[0006] Example 4. The apparatus according to any one of Examples 1 to 3, wherein the at least one tissue manipulator is an elastically deflectable tissue manipulator configured to be elastically deflected toward the inner wall surface by the tissue entering the lumen through the distal opening, and to recover from the deflection when the axial advancement of the hollow sampling portion into the body tissue stops.

[0007] Example 5. The apparatus according to any one of Examples 1 to 4, wherein the at least one tissue manipulator is a portion cut out of the wall of the sampling section.

[0008] Example 6. The apparatus according to any one of Examples 1 to 5, wherein the at least one tissue manipulator is formed of the material of the wall.

[0009] Example 7. The apparatus according to any one of Examples 1 to 6, wherein the at least one tissue manipulator is formed by forming an arcuate incision across the wall, and wherein the width of the incision is between 0.005 mm and 0.05 mm.

[0010] Example 8. The apparatus according to any one of Examples 1 to 7, wherein the at least one tissue manipulator includes a distal end and a proximal end, the distal end being coupled to or integrally located with the wall near the distal end of the sampling portion, the proximal end being configured to be positioned within the lumen, and wherein the distal end of the at least one tissue manipulator is located at a distance between 0.1 mm and 20 mm from the distal end of the sampling portion, or at a distance of up to 4 times the internal width of the sampling portion from the distal end of the sampling portion.

[0011] Example 9. The apparatus according to any one of Examples 1 to 8, wherein the distal end of the at least one tissue manipulator is located at the level of and / or aligned with the wall of the hollow sampling portion.

[0012] Example 10. The apparatus according to any one of Examples 1 to 9, wherein the radius of curvature of the at least one tissue manipulator between the distal end and the proximal end is the radius of curvature of the wall of the hollow sampling portion.

[0013] Example 11. The apparatus according to any one of Examples 1 to 10, wherein the radius of curvature of the at least one tissue manipulator between the distal end and the proximal end is at most 30% smaller or larger than the radius of curvature of the wall of the hollow sampling portion.

[0014] Example 12. The apparatus according to any one of Examples 1 to 11, wherein the at least one tissue manipulator is straight between the distal end and the proximal end.

[0015] Example 13. The apparatus according to any one of Examples 1 to 12, wherein the at least one tissue manipulator has an inclination angle between 5 degrees and 30 degrees with respect to a plane perpendicular to the long axis of the sampling portion.

[0016] Example 14. The device according to any one of Examples 1 to 13, wherein the at least one tissue manipulator is formed of a superelastic and / or shape memory alloy.

[0017] Example 15. The apparatus according to any one of Examples 1 to 14, wherein the at least one tissue manipulator is configured to form a tissue separation region in the tissue by moving back toward the lumen and applying force to the tissue in the lumen, wherein the tissue separation region is a region that is easier to separate than other regions of the body tissue portion.

[0018] Example 16. The apparatus according to any one of Examples 1 to 15, wherein the at least one tissue manipulator is configured to form a tissue separation region in the tissue by moving back toward and penetrating into the lumen, wherein the tissue separation region is a region that is easier to separate than other regions of the body tissue portion.

[0019] Example 17. The apparatus according to any one of Examples 1 to 16, wherein when the hollow sampling portion is rotated and / or retracted, the hollow sampling portion applies a force to the tissue in the cavity, the force being sufficient to separate the tissue sample from the tissue at the tissue separation region.

[0020] Example 18. The apparatus according to any one of Examples 15 to 17, wherein the hollow sampling portion is axially advanced into the body tissue while rotating in a first direction, and wherein the at least one movable tissue manipulator is configured to form the tissue separation region when the axial advancement stops and when the hollow sampling portion rotates in the opposite second direction.

[0021] Example 19. The apparatus according to any one of Examples 1 to 18, wherein the at least one tissue manipulator includes a tissue-penetrating edge configured to contact tissue in the lumen and to form the separation region by forming at least a partially circumferential groove or at least a partially circumferential slit in the tissue when the hollow sampling portion is rotated.

[0022] Example 20. An apparatus according to any one of Examples 1 to 19, wherein the at least one tissue manipulator comprises at least two tissue manipulators, each of the tissue manipulators having a tissue contact end configured to contact the tissue in the lumen, wherein when each of the at least two tissue manipulators is fully extended into the lumen, the tissue contact ends of the at least two tissue manipulators are located on a single plane substantially perpendicular to the long axis.

[0023] Example 21. An apparatus according to any one of Examples 1 to 20, comprising at least one actuator and a shaft having a distal end and a proximal end, wherein the at least one actuator is coupled to the proximal end of the shaft and the hollow sampling portion is coupled to the distal end of the shaft, and wherein the shaft is configured to rotate and / or axially advance the hollow sampling portion within the body tissue.

[0024] Example 22. An apparatus according to any one of Examples 1 to 21, wherein when the sampling portion is axially advanced into the body tissue, the shaft rotates the sampling portion in a first direction, and wherein rotating the sampling portion in the opposite second direction by the shaft forms a tissue separation region and / or separates the tissue sample from the tissue in the lumen.

[0025] Example 23. The apparatus according to any one of Examples 1 to 22, wherein the at least one actuator is configured to rotate the sampling portion at a tangential speed between 2.5 and 1000 mm / sec.

[0026] Example 24. The apparatus according to any one of Examples 1 to 23, wherein the at least one actuator is configured to axially advance the sampling portion at an axial velocity between 1 and 100 mm / sec.

[0027] Example 25. The apparatus according to any one of Examples 1 to 24, wherein the ratio between the axial velocity and the tangential velocity of the sampling portion is between 1 and 10.

[0028] Example 26. The apparatus according to any one of Examples 1 to 25, wherein the ratio between the axial velocity and the tangential velocity of the sampling portion is between 2 and 5.

[0029] Example 27. The apparatus according to any one of Examples 1 to 26, wherein the shaft is a flexible shaft.

[0030] Example 28. The apparatus according to any one of Examples 1 to 27, wherein the shape and size of the sampling portion are designed to advance toward the body tissue within the working channel of the endoscope.

[0031] Example 29. The apparatus according to any one of Examples 1 to 28, wherein the hollow sampling portion includes a sampling needle.

[0032] Example 30. The apparatus according to any one of Examples 1 to 29, wherein the distal end of the sampling portion is substantially perpendicular to the long axis of the sampling portion.

[0033] Example 31. The apparatus according to any one of Examples 1 to 30, wherein the distal end of the sampling portion includes an inner sharpened edge and / or an outer sharpened edge, the edges surrounding the distal opening and configured to form a circular incision through the body tissue during axial advancement and / or rotation of the sampling portion into the body tissue.

[0034] Example 32. A method for tissue sampling, comprising: a. The sampling portion of the biopsy device is axially advanced into body tissue, wherein during the axial advancement, a portion of the body tissue enters the lumen of the sampling portion, and at least one tissue manipulator extending from the wall of the sampling portion into the lumen is pushed outward toward the wall; b. When the at least one tissue manipulator retracts into the cavity, force is applied to the body tissue portion by the at least one tissue manipulator; c. Forming a tissue separation region in the body tissue portion, wherein the tissue separation region is a region that is more easily separated from other regions of the body tissue portion in the cavity in response to the application of a separation force to the body tissue portion; d. By applying the separation force to the body tissue portion, the tissue sample is separated from the body tissue portion at the tissue separation region.

[0035] Example 33. The method according to Example 32, wherein the at least one tissue manipulator comprises two or more tissue manipulators, and wherein the application comprises grasping the body tissue portion in the cavity by the two or more tissue manipulators as the two or more tissue manipulators retract into the cavity.

[0036] Example 34. The method according to Example 32 or 33, wherein forming the tissue separation region by means of the at least one tissue manipulator includes rotating the at least one tissue manipulator while applying the force to form at least a partially circumferential groove or slit in the body tissue portion.

[0037] Example 35. The method according to any one of Examples 32 to 34, comprising rotating the sampling portion and the at least one tissue manipulator during the formation to form the at least partially circumferential groove or slit in the body tissue portion while the at least one tissue manipulator applies the force to the body tissue portion.

[0038] Example 36. The method according to any one of Examples 32 to 35, wherein the axial advance comprises axial advance while rotating the sampling portion relative to the body tissue in a first direction, and wherein the formation comprises forming the tissue separation region by rotating the sampling portion and the at least one tissue manipulator in the opposite second direction while applying the force to the body tissue portion via the at least one tissue manipulator.

[0039] Example 37. The method according to any one of Examples 32 to 36, comprising stopping the axial advance before forming the tissue separation region.

[0040] Example 38. The method according to any one of Examples 32 to 37, wherein the separation comprises applying a shear force to the body tissue portion by rotating the sampling portion relative to the body tissue located outside the sampling portion to separate the tissue sample.

[0041] Example 39. The method according to any one of Examples 32 to 38, wherein the separation comprises separating the tissue sample by retracting the sampling portion from the body tissue and applying a tearing force to the body tissue portion.

[0042] Example 40. The method according to any one of Examples 32 to 39, comprising repeating the axial advance, the application, the formation, and the separation to obtain at least one additional tissue sample from the body tissue.

[0043] Example 41. The method according to any one of Examples 32 to 40, wherein the axial advance comprises axially advancing the sampling portion into the body tissue at an axial velocity between 1 and 100 mm / sec.

[0044] Example 42. The method according to any one of Examples 32 to 41, wherein the axial advance includes rotating the sampling portion at a tangential speed between 2.5 and 1000 mm / sec during the axial advance.

[0045] Example 43. The method according to Example 42, wherein the ratio between the axial velocity and the tangential velocity is in the range of 3 to 5.

[0046] Example 44. A soft tissue biopsy device, comprising: a. A slender handle, including gripping components; b. A slender, flexible shaft mechanically comprising a hollow distal sampling portion having an inner cavity and a distal opening facing soft tissue; c. At least one drive unit is configured to rotate the sampling portion as it is axially advanced into the soft tissue; The ratio between the tangential rotational speed and the axial propulsion speed of the sampling section is between 1 and 10.

[0047] Example 45. The apparatus according to Example 44, wherein the at least one drive unit rotates the elongated flexible shaft at a tangential speed in the range of 2.5 to 1000 mm / sec.

[0048] Example 46. The apparatus according to any one of Examples 44 or 45, wherein the at least one drive unit axially advances the sampling portion at an axial velocity in the range of 1 to 100 mm / sec.

[0049] Example 47. The apparatus according to any one of Examples 44 to 46, wherein the distal opening is located at the distal end of the sampling portion, and wherein the distal end of the sampling portion is a flat straight end or substantially perpendicular to the long axis of the sampling portion.

[0050] Example 48. The apparatus according to any one of Examples 44 to 47, wherein the ratio is between 2 and 5.

[0051] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While similar or equivalent methods and materials to those described herein may be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In the event of conflict, the patent specification, including the definitions, shall prevail. Furthermore, materials, methods, and examples are illustrative only and are not necessarily intended to be limiting.

[0052] Brief description of the attached figures Some embodiments of the present invention are described herein by way of example only with reference to the accompanying drawings. Referring now to the detailed drawings, it should be emphasized that the details shown are by way of example and are intended to illustrate embodiments of the invention. In this regard, the description taken in conjunction with the drawings will make it clear to those skilled in the art how to practice embodiments of the invention.

[0053] In the attached diagram: Figure 1a This is a flowchart of a general process for creating separated regions in an organization according to some embodiments of the present invention; Figures 1b-1e This is a schematic diagram of a process for creating a separation region in a tissue according to some embodiments of the present invention; Figure 1f This is a flowchart of a tissue sampling process according to some embodiments of the present invention; Figure 2 This is a schematic diagram showing the positional changes of a flexible cutter during tissue sampling according to some embodiments of the present invention; Figures 3a-3b This is a schematic diagram of a biopsy device sampling portion according to some embodiments of the present invention, when at least one cutter is aligned with the wall of the sampling portion (3A) and when at least one cutter extends inward into the inner cavity of the sampling portion (3B). Figure 3c-3e This is a schematic diagram showing the orientation of two cutters extending into the inner cavity of the sampling portion according to some embodiments of the present invention; Figure 3f This is a block diagram of a tissue sampling device according to some exemplary embodiments of the present invention; Figure 4 This is a flowchart illustrating the detailed tissue sampling process according to some embodiments of the present invention; Figures 5a-5h This is a schematic diagram illustrating the tissue sampling process according to some embodiments of the present invention; Figures 6a-6g This is a schematic diagram showing the extraction of tissue samples from the lumen of the sampling portion of a biopsy device according to some embodiments of the present invention; Figures 7a-7e This is a schematic diagram of the sampling portion of a cutter having an extension extending inward from the wall of the sampling portion into the lumen of the sampling portion, according to some embodiments of the present invention; and Figures 8a-8b This is a schematic diagram of a tissue manipulator, such as a cutter, according to some exemplary embodiments of the present invention.

[0054] Detailed embodiments of the present invention In some embodiments, the present invention relates to tissue sampling, and more specifically, but not exclusively, to soft tissue sampling for biopsy.

[0055] Overview One aspect of some embodiments of the present invention relates to separating a tissue sample from tissue within the lumen of a biopsy device using at least one tissue manipulator extending from the wall of the biopsy device into the lumen. In some embodiments, the at least one tissue manipulator is positioned within the lumen in an orientation suitable for forming a separation region (e.g., a separation plane) in the tissue, for example by reducing the width (e.g., diameter) or amount of the tissue in the separation region. In some embodiments, the separation region is a region within the tissue that connects two tissue portions on either side of the separation region and where the connection force is weakened. In some embodiments, when a shear force is applied to the tissue, a separation or gap is formed between the two tissue portions on either side of the separation region or the separation plane.

[0056] According to some exemplary embodiments, the tissue manipulator manipulates tissue within the lumen of a biopsy device via at least one manipulator, forming incisions in the tissue, forming grooves in the tissue, and / or grasping the tissue by penetrating, for example, through the tissue. In some embodiments, the tissue manipulator forms circumferential or arcuate incisions in the tissue, at least partially surrounding the tissue. Alternatively, the tissue manipulator forms circumferential or arcuate grooves in the tissue, at least partially surrounding the tissue.

[0057] According to some embodiments, the tissue manipulator includes at least one movable extension that extends into the lumen of a biopsy device, for example, extending from a wall of the biopsy device surrounding the lumen. In some embodiments, the movable extension includes a cutter, optionally flexible, such as cutting teeth, extending from the wall of the biopsy device into the lumen. In some embodiments, the at least one flexible cutter is part of the biopsy device wall and is configured to bend inward into the biopsy device lumen in a relaxed state. In some embodiments, the at least one flexible cutter is configured to move between a first state and a second state, in which the proximal end of the flexible cutter is substantially aligned with or substantially adjacent to the biopsy device wall, and in a second state, the proximal end of the flexible cutter moves inward into the biopsy device lumen, optionally while the distal end of the flexible cutter remains coupled to or integral with the wall. In some embodiments, the distal end of the tissue manipulator, such as the cutter, is located at the level of the sampling portion wall and / or aligned with the hollow portion wall.

[0058] According to some exemplary embodiments, when tissue penetrates into the lumen of the biopsy device, for example, when the biopsy device is axially moved into the tissue, the penetrating tissue pushes the at least one movable extension (e.g., the proximal end of the movable extension) against the wall, optionally entering a first state. In some embodiments, when axial advancement into the tissue stops, the at least one movable extension (e.g., the proximal end of the movable extension) moves inward or bends into the lumen and optionally penetrates into the tissue within the lumen.

[0059] According to some embodiments, at least a portion of the movable extension (e.g., a flexible cutter) is coupled to or integrated with the wall of the biopsy device. In some embodiments, the flexible cutter is a portion of the biopsy device wall that is cut out, such as the wall of the sampling portion (e.g., the sampling needle) of the biopsy device.

[0060] According to some embodiments, the angle (e.g., pitch angle) between the movable extension (e.g., a flexible cutter) and a plane perpendicular to the long axis of the biopsy device is in the range of 5 to 30 degrees, for example, in the range of 10 to 20 degrees, in the range of 10 to 15 degrees, in the range of 12 to 15 degrees, in the range of 12 to 17 degrees, in the range of 13 to 18 degrees, in the range of 12 to 30 degrees, or any intermediate, smaller, or larger pitch angle or pitch angle range toward the proximal end of the biopsy tube.

[0061] According to some embodiments, the distal end of the flexible cutter, away from its base, includes a cutting edge. In some embodiments, the flexible cutter is rotated along the direction of the distal cutting edge to cut tissue in contact with the flexible cutter. In some embodiments, the at least one flexible cutter includes at least two flexible cutters extending into the lumen of the biopsy device from at least two locations on the circumference of the wall. Optionally, these two locations have similar axial positions along the length of the biopsy device. Optionally, these two locations are relative positions on the circumference of the biopsy device wall. In some embodiments, the at least two flexible cutters have similar orientations between the base and distal end of each flexible cutter, for example, along the rotation path of the biopsy tube.

[0062] One aspect of some embodiments of the invention relates to introducing tissue into the lumen of a biopsy device needle while rotating it in a first direction, and forming a circumferential groove, such as a circumferential incision, in the tissue within the lumen by rotating the needle in a second direction opposite to the first direction. In some embodiments, the tissue is shaped by a tissue manipulator extending into the lumen. In some embodiments, the tissue manipulator is a cutter extending from the wall of the biopsy device needle into the lumen, configured to cut the tissue as the biopsy tube rotates in the second direction. In some embodiments, the circumferential incision or circumferential groove is formed in a single cutting plane, for example, to reduce the diameter of the tissue in the cutting plane.

[0063] Although tissue manipulators are described herein as cutters that create incisions in tissue, it should be noted that tissue manipulators can pinch or create partial or complete grooves in tissue, such as circumferential or arcuate grooves, and incisions in tissue are an example of grooves. In some embodiments, the grooves form separation regions, which are areas where tissue is more likely to break or separate. In some embodiments, rotation and / or retraction of the biopsy tube causes the tissue sample to tear from the tissue within the biopsy tube lumen, optionally without the need to create an incision in the tissue.

[0064] Alternatively or additionally, the tissue manipulator is used to grasp tissue and thus functions as a tissue gripper. In some embodiments, grasping tissue allows force to be applied to the tissue by rotation and / or axial retraction of the sampling portion, for example, separating the grasped tissue from the tissue in the lumen of the biopsy device located distal to the tissue manipulator when the biopsy device is retracted.

[0065] One potential advantage of having a separation region in a single plane is that it can separate the proximal tissue sample that continues to flow within the sampling section lumen from the distal tissue that continues to connect to the organ tissue. If the tissue manipulator is not located in a similar axial position within the sampling section, then after the tissue sample is separated, the tissue may be captured by the tissue manipulator and obstruct the tissue from entering the sampling section.

[0066] An additional potential advantage of having a tissue manipulator that extends into the lumen of the sampling portion may be a reduction in the cross-sectional area of ​​the sampling portion, for example, to prevent bodily fluids (e.g., blood) from entering the sampling portion and contaminating the tissue sample, especially when a sampling needle with an inner diameter greater than 0.4 mm is optionally used.

[0067] One aspect of some embodiments relates to a biopsy apparatus having a hollow distal sampling portion configured to separate a tissue sample from body tissue by axially advancing it while rotating at a fixed or varying rotational speed. In some embodiments, the ratio between the tangential rotational speed and the axial advancement speed of the sampling portion is between 1 and 10, for example, between 3.5 and 4.5, or for example, between 2 and 5. In some embodiments, the hollow sampling portion advances and rotates axially at the aforementioned ratio, applying a force sufficient to separate the tissue sample from the body tissue portion located within the cavity of the sampling portion, such that it can be described, for example, in International Patent Application Publication No. WO2019155472A1, the entire contents of which are incorporated herein by reference.

[0068] According to some embodiments, the sampling portion rotates at a tangential speed in the range of 2.5-1000 mm / sec, such as 2.5-40 mm / sec, 30-40 mm / sec, 35-45 mm / sec, 30-50 mm / sec, 10-100 mm / sec, 50-500 mm / sec, 300-1000 mm / sec, or any intermediate, smaller, or larger value. Furthermore, during rotation, the sampling portion is axially advanced into the tissue at an axial speed in the range of 1-100 mm / sec, such as 1-10 mm / sec, 5-12 mm / sec, 5-15 mm / sec, 5-50 mm / sec, 10-100 mm / sec, or any intermediate, smaller, or larger value. According to some exemplary embodiments, the biopsy device includes at least one drive unit, such as a motor for rotating the sampling portion and / or for axially advancing the sampling portion. In some embodiments, the biopsy apparatus includes at least two motors, at least one motor for rotating the sampling portion and at least one different motor for axially advancing the sampling portion. In some embodiments, the hollow distal sampling portion is coupled to or integrated into the distal end of a shaft (e.g., a flexible shaft). In some embodiments, the shaft (e.g., the proximal end of the flexible shaft) is coupled to the at least one motor. In some embodiments, the shaft is configured to transmit power and / or force from the at least one motor to the sampling portion. Examples of biopsy apparatuses are described in International Patent Application Publication No. WO2019155472A1, the entire contents of which are incorporated herein by reference.

[0069] According to some exemplary embodiments, when axially advanced and rotated at the aforementioned ratio, the sampling portion includes at least one tissue manipulator as described in this patent application. Alternatively, when axially advanced and rotated at the aforementioned ratio, the sampling portion does not include the at least one tissue manipulator. In some embodiments, the sampling portion is the sampling portion described in this application with or without the at least one tissue manipulator.

[0070] One potential advantage of rotating and axially advancing the sampling portion into the body tissue at a specific ratio range is that it can prevent damage to the body tissue outside the sampling portion, while allowing the biopsy device to efficiently separate long and intact tissue samples from the body tissue portion located inside the cavity of the sampling portion.

[0071] Before explaining at least one embodiment of the present invention in detail, it should be understood that the invention is not necessarily limited in its application to the construction details and arrangements of components and / or methods set forth in the following description and / or drawings and / or examples. The invention can have other embodiments or be practiced or performed in various ways.

[0072] Exemplary organization separation According to some exemplary embodiments, a biopsy device including a sampling portion includes at least one tissue manipulator extending into the lumen of the sampling portion. In some embodiments, the at least one tissue manipulator includes two or more tissue manipulators. Optionally, the two or more tissue manipulators have similar axial positions along the length of the lumen of the sampling portion.

[0073] According to some exemplary embodiments, the at least one tissue manipulator is a movable tissue manipulator configured to move between a first position (e.g., a first state) and a second position (e.g., a second state). In some embodiments, the movable tissue manipulator is an elastic tissue manipulator, such as an elastically deflectable tissue manipulator. In some embodiments, the elastically deflectable tissue manipulator is configured such that, for example, when a force is applied to the tissue manipulator, it moves from the first position to the second position, and returns to the first position when the force is stopped or the force applied to the tissue manipulator decreases.

[0074] According to some exemplary embodiments, the position, shape, and size of the at least one tissue manipulator are designed to penetrate tissue that has penetrated into a lumen, for example, when the sampling portion is rotated and axially advanced (optionally simultaneously) into the body tissue. In some embodiments, the at least one tissue penetrator penetrates the tissue within the lumen to form a tissue separation region. In some embodiments, the tissue separation region is a region within the tissue that is easily separable. In some embodiments, a force (e.g., tearing or shearing force) is applied to the tissue at the tissue separation region to separate the tissue sample from the body tissue that has penetrated into the lumen.

[0075] Now for reference Figure 1a It describes a tissue separation process according to some exemplary embodiments of the present invention, such as by creating tissue separation regions in the tissue.

[0076] According to some exemplary embodiments, at block 100, body tissue is introduced into the lumen of the sampling portion of the biopsy device. In some embodiments, the body tissue is introduced into the lumen as the sampling portion is axially advanced into the body tissue. Optionally, the body tissue is introduced into the lumen as the sampling portion is advanced into the body tissue while rotating. In some embodiments, the body tissue is introduced into the lumen through a distal opening of the sampling portion.

[0077] According to some exemplary embodiments, at block 101, at least one tissue manipulator penetrates into body tissue. In some embodiments, the at least one tissue manipulator extends into the lumen of a sampling portion of a biopsy device. In some embodiments, as the sampling portion is advanced into the body tissue, the at least one tissue manipulator penetrates into the body tissue within the lumen. In some embodiments, as the sampling portion is axially advanced into body tissue outside the sampling portion, optionally, the at least one tissue penetrator penetrates into the body tissue within the lumen while the sampling portion is rotated.

[0078] According to some exemplary embodiments, when the axial advance of the sampling portion stops, the at least one tissue manipulator penetrates into the body tissue within the cavity of the sampling portion, and optionally, when the force applied to the tissue manipulator decreases, the tissue penetrator is allowed to recover from deflection.

[0079] According to some exemplary embodiments, at block 105, the at least one tissue manipulator forms a separation region within body tissue within the lumen. In some embodiments, the separation region is a region within the tissue in which the tissue is more easily separated than in other regions of the tissue. In some embodiments, the at least one tissue manipulator forms the separation region by forming an incision in the body tissue, such as a circumferential incision or an arcuate incision (optionally at least partially surrounding the body tissue). Alternatively or additionally, the at least one tissue manipulator forms the separation region by forming a groove in the body tissue, such as a circumferential groove or an arcuate groove (optionally at least partially surrounding the body tissue). Alternatively or additionally, the at least one tissue manipulator forms the separation region by grasping the body tissue, for example by engaging or increasing the engagement between the at least one tissue manipulator and the body tissue, optionally by increasing the friction or grasping force between them.

[0080] According to some exemplary embodiments, at block 107, a tissue sample is separated from the body tissue. In some embodiments, the tissue sample is separated from the body tissue at a separation region. In some embodiments, the tissue sample is separated from the body tissue by applying a force, such as a tearing force and / or a shearing force, to the tissue at the separation region. In some embodiments, the tissue sample is separated by rotating the sampling portion. Alternatively or additionally, the tissue sample is separated from the body tissue by pulling out or retracting the sampling portion.

[0081] Now for reference Figures 1b-1e It describes a process of tissue sampling by forming a separation region in the tissue according to some exemplary embodiments of the present invention.

[0082] According to some exemplary embodiments, for example Figure 1bAs shown, at least one tissue manipulator, such as tissue manipulators 109 and 111, penetrates into a portion 113 of body tissue 115 located within the lumen 117 of the sampling portion 119. In some embodiments, the tissue manipulator penetrates into the tissue 113 and into the body tissue 115 during axial and / or rotational movement of the sampling portion. Alternatively, the tissue manipulator penetrates into the tissue 113 when the movement (e.g., axial movement) of the sampling portion 119 into the body tissue 115 ceases.

[0083] According to some exemplary embodiments, the movement of tissue manipulators, such as manipulators 109 and 111, forms a separation region 121 in the tissue portion 113 located within the cavity 117, for example... Figure 1c As shown. In some embodiments, the formed separation region is a region within the tissue that is more sensitive to forces applied to the tissue, causing tissue 113 to separate at tissue separation region 121. In some embodiments, for example Figure 1c As shown, the width (e.g., diameter) of the tissue in the separation region 121 is smaller than the width of the tissue distal to and / or proximal to the region 121. In some embodiments, the separation region 121 is a region that concentrates the force applied to the tissue 113 within the sampling region, causing two portions of the tissue 113 to tear or separate at the separation region 121.

[0084] According to some exemplary embodiments, for example Figure 1d As shown, when the tissue manipulator is located within the separation region, the sampling portion retracts and / or rotates along the rotation direction 139, applying a force, such as tearing force and / or shearing force, to the tissue 113 at the separation region 121. In some embodiments, for example... Figure 1e As shown, the applied force causes a sample, such as tissue sample 123 located within the cavity 117 and proximal to manipulators 111 and 109, to separate from the remaining portion of tissue 113 located inside and outside the cavity 117. In some embodiments, the remaining portion of tissue 113 is located at the separation region and / or distal to manipulators 109 and 111.

[0085] According to some exemplary embodiments, the formation of the separation region 121 allows, for example, determining the position of the separation plane between the tissue sample 123 and the remainder of the body tissue 113 located within the cavity 117.

[0086] Exemplary general tissue sampling process According to some exemplary embodiments, a biopsy device is used to sample soft tissue, such as to obtain a biopsy sample from soft tissue of the body (e.g., tissue from the pancreas, liver, at least one lymph node, lung, spleen, and / or glands such as the thyroid gland). In some embodiments, the biopsy device is used to sample tissue suspected of being cancerous. In some embodiments, the sampling portion of the biopsy device, such as a sampling needle located in a distal segment of the biopsy device, is axially advanced into the tissue simultaneously, synchronously, and optionally at a specific ratio while rotating. In some embodiments, when the sampling portion rotates in a direction opposite to the direction of rotation used when penetrating the tissue, the tissue sample separates from the tissue entering the sampling portion.

[0087] Now for reference Figure 1f It describes a process for sampling soft tissue, such as sampling a volume within soft tissue that optionally includes cancerous tissue or a tumor, according to some exemplary embodiments of the present invention.

[0088] According to some exemplary embodiments, at block 102, the biopsy device is advanced toward the target tissue. In some embodiments, a flexible shaft with a sampling portion (e.g., a sampling needle) at its end is advanced toward the target tissue. In some embodiments, the flexible shaft with the sampling portion at its end is advanced toward the target tissue within and / or via the working channel of the endoscope. In some embodiments, the sampling portion includes at least one tissue manipulator, such as a cutter configured to extend into the lumen of the sampling portion.

[0089] According to some exemplary embodiments, during advancement toward the target tissue at block 102, the lumen may optionally be blocked by a tissue penetrator. In some embodiments, the distal tip of the tissue penetrator extends at least partially through a distal opening of the sampling portion facing the tissue and is configured to form an incision, such as a fine incision in the tissue wall, as described in, for example, WO2022003691A1, the entire contents of which are incorporated herein by reference. In some embodiments, when the lumen is blocked by the tissue penetrator, the tissue penetrator body in the lumen pushes the at least one tissue manipulator against a wall, such as the inner surface of the wall of the sampling portion.

[0090] According to some exemplary embodiments, at block 103, the tissue penetrator may optionally be removed from the lumen. In some embodiments, the tissue penetrator is removed by retracting it from the lumen. In some embodiments, removing the tissue penetrator releases the obstruction to the sampling portion of the lumen and optionally allows the at least one tissue manipulator to move into the lumen, for example, to recover from a tissue manipulator deflection caused by the tissue penetrator.

[0091] According to some exemplary embodiments, at block 104, the sampling portion is axially advanced into body tissue, such as soft tissue, while rotating about the long axis of the sampling portion. In some embodiments, the sampling portion is advanced into the body tissue, introducing the body tissue into the lumen of the sampling portion. In some embodiments, the body tissue enters the lumen through a distal opening of the sampling portion and optionally enters outside or near the axial position of the at least one tissue manipulator (e.g., the at least one cutter within the lumen).

[0092] According to some exemplary embodiments, at block 106, movement of the sampling portion is stopped. In some embodiments, stopping the movement includes stopping both axial and rotational movement of the sampling portion. Alternatively, stopping the movement includes stopping axial movement of the sampling portion within the tissue while optionally maintaining rotation of the sampling portion.

[0093] According to some exemplary embodiments, at block 108, the sampling portion is rotated in the opposite direction. In some embodiments, the sampling portion rotates in the opposite direction to the rotation direction used when advancing the sampling portion axially into the tissue at block 104.

[0094] According to some exemplary embodiments, at block 110, the tissue manipulator creates a separation region in the body tissue. In some embodiments, at block 110, the tissue manipulator creates the separation region, for example, to separate the tissue sample from the body tissue by forming an incision or groove, such as a circumferential incision or circumferential groove, in the body tissue within the lumen. In some embodiments, at block 108, as the sampling portion rotates, the tissue manipulator manipulates the tissue, for example, by cutting or forming a groove, and separates the tissue sample from the body tissue.

[0095] According to some exemplary embodiments, at block 112, the separated tissue sample is removed from the lumen of the sampling portion. In some embodiments, the separated tissue sample is removed from the lumen via a distal opening of the sampling portion. Alternatively, the separated tissue sample is removed via a proximal opening of the sampling portion, for example, when the sampling portion is separated from an axis used to rotate the sampling portion, or when the sampling portion is disassembled, for example, to extract the separated tissue sample.

[0096] Exemplary state of a movable cutter According to some exemplary embodiments, the sampling portion of a biopsy device includes at least one internal cutter extending from the wall of the sampling portion into an inner cavity (in which tissue is introduced from the outside). In some embodiments, the internal cutter is integrated with or coupled to the wall of the sampling portion. In some embodiments, as the sampling portion advances into body tissue, a portion of the body tissue is introduced into the inner cavity through a distal opening of the sampling portion and contacts the at least one internal cutter. In some embodiments, the at least one internal cutter is a movable internal cutter, and optionally a flexible internal cutter, configured to move between a first position and a second position, wherein in the first position the internal cutter extends into the inner cavity and in the second position the internal cutter is pushed against the wall of the sampling portion.

[0097] According to some exemplary embodiments, the inner cutter is configured to extend into the cavity of the sampling portion in a relaxed state (e.g., when no mechanical force is applied to the inner cutter). In some embodiments, when the inner cutter is pushed against the wall of the sampling portion, the inner cutter at least partially penetrates into an opening, such as a cutout window in the wall of the sampling portion.

[0098] Now for reference Figure 2 It depicts the state changes of the cutter within a biopsy apparatus according to the tissue sampling stage, based on some exemplary embodiments of the present invention.

[0099] According to some exemplary embodiments, at block 204, the sampling portion of the biopsy device is positioned next to the body tissue to be sampled and then penetrates into the body tissue. In some embodiments, at block 204, the sampling portion is fixed in position, and the body tissue is outside the internal volume of the sampling portion. In some embodiments, at block 204, the at least one movable internal cutter bends into the internal volume of the sampling portion. In some embodiments, at block 204, the movable internal cutter extends inward from the wall of the sampling portion into the internal volume and is optionally in a relaxed state.

[0100] According to some exemplary embodiments, at block 206, a sampling portion is advanced into body tissue. In some embodiments, the sampling portion is axially advanced while rotating about the long axis of the sampling portion. In some embodiments, during the advancement of the sampling portion, body tissue enters the cavity of the sampling portion while simultaneously connecting with body tissue outside the sampling portion. In some embodiments, the body tissue entering the cavity pushes the at least one internal cutter against the wall of the sampling portion, for example, against an opening in the wall. Optionally, the at least one internal cutter is pushed against the wall of the sampling portion until the at least one internal cutter is at least partially substantially aligned with the wall, for example, positioned at an angle of less than 7 degrees relative to the wall, such as less than 5 degrees, less than 3 degrees, or any intermediate, smaller, or larger angle.

[0101] According to some exemplary embodiments, at block 206, body tissue entering the lumen is advanced to a position within the lumen proximal to the at least one internal cutter, such as between the internal cutter and the proximal opening or proximal end of the biopsy device.

[0102] According to some exemplary embodiments, at frame 208, movement of the sampling portion into the body tissue is stopped. In some embodiments, at frame 208, axial advancement of the sampling portion into the body tissue and / or movement of the body tissue within the lumen of the sampling portion is stopped. Furthermore, rotation of the sampling portion is stopped at frame 208. In some embodiments, at frame 208, at least one elongated portion of the body tissue is located between the proximal position of the inner cutter and the distal opening of the sampling portion within the lumen, and optionally remains connected to the body tissue outside the sampling portion.

[0103] According to some exemplary embodiments, at block 208, when the movement of the sampling portion stops, the cutter bends inward into the inner cavity and enters body tissue, such as soft tissue, within the cavity. In some embodiments, in the bent position, such as when the inner cutter extends into the inner cavity, the angle between the at least one inner cutter and the wall of the sampling portion is greater than 5 degrees, for example, greater than 10 degrees, greater than 20 degrees, greater than 30 degrees, greater than 45 degrees, or any intermediate, smaller, or larger angle value. In some embodiments, in the bent position, the angle between the inner cutter and the wall of the sampling portion is in the range of 5 to 60 degrees, for example, between 15 to 50 degrees, between 20 to 45 degrees, between 10 to 30 degrees, or any intermediate, smaller, or larger angle range.

[0104] According to some exemplary embodiments, at block 210, the sampling portion is rotated, optionally in a direction opposite to the direction of rotation when the sampling portion is advanced into the body tissue at block 206. In some embodiments, a movable cutter cuts and at least partially separates the sample from the body tissue located within the lumen of the sampling portion. In some embodiments, rotation of the sampling portion causes the inner cutter to rotate and form a circumferential incision through the body tissue, thereby at least partially separating the tissue sample located proximal to the inner cutter from the body tissue located within the sampling portion.

[0105] Exemplary sampling portion of a biopsy device According to some exemplary embodiments, the sampling portion (e.g., a sampling needle) of a biopsy device has an elongated, optionally tubular body with a distal opening leading to an inner cavity of the tubular body. In some embodiments, the body has a tapered distal end surrounding the distal opening, the shape and size of which are designed to allow penetration of body tissue, such as soft tissue. In some embodiments, the distal end (e.g., the tapered distal end) penetrates into the tissue, forming a circular incision in the tissue, allowing a portion of the tissue body to enter the inner cavity of the body through the distal opening. In some embodiments, the sampling portion includes at least one, such as two, three, four, five, six, or any greater number of tissue manipulators, such as internal cutters, extending from the wall of the sampling portion into the inner cavity. In some embodiments, the internal cutters are configured to form an incision in a portion of body tissue located within the inner volume, resulting in at least partial separation of the tissue sample from the portion of body tissue.

[0106] Now for reference Figure 3a It depicts a longitudinal cross-sectional view of a sampling portion of a biopsy device according to some exemplary embodiments of the present invention, the sampling portion including at least one, for example at least two, internal cutters.

[0107] According to some exemplary embodiments, the sampling portion of a biopsy device (e.g., sampling portion 302) includes an elongated hollow body 304 having an inner cavity 306, a long axis 308, a distal end portion 310, and a proximal end portion 312. In some embodiments, the body includes a distal opening 314 at the distal end portion 310 leading to the inner cavity 306.

[0108] According to some exemplary embodiments, the distal end is a flat, straight end. In some embodiments, the distal end is substantially perpendicular to the long axis of the sampling portion. As used herein, substantially perpendicular means a deviation from a 90-degree angle of less than 5%. Alternatively, in some embodiments, the distal end is a beveled end. In some embodiments, the sampling portion body has a circular, elliptical, or ellipsoidal cross-section, for example at the distal end 310. In some embodiments, the sampling portion body is tubular, for example, to allow tissue to enter the lumen 306 through the distal opening 314.

[0109] According to some exemplary embodiments, the sampling portion includes at least one tissue manipulator, such as at least two tissue manipulators. In some embodiments, the at least two tissue manipulators include at least two internal cutters 316 and 318. In some embodiments, the at least two cutters 316 and 318 are coupled to a wall 320 surrounding the body 304 of the cavity. Alternatively, the at least two cutters 316 and 318 are partial cutouts of the wall 320. In some embodiments, a coupling region between each cutter 316 and 318 and the wall, such as coupling regions 315 and 317 respectively, is located at a distance 322 from the distal end 310 or the distal opening 314. In some embodiments, the coupling region serves as a hinge region. In some embodiments, the coupling region allows, for example, the cutters 316 and 318 to resiliently deflect toward the wall and recover from the deflection by, for example, bending inward, back into the cavity 306.

[0110] In some embodiments, distance 322 is the axial distance from the distal end 310 of the sampling portion to the axial position of one or more of the inner cutters, in the range of 0.1 mm to 50 mm, for example, between 0.2 mm and 20 mm, 2 mm and 15 mm, 4 mm and 12 mm, or any intermediate, smaller, or larger value. In some embodiments, distance 322 is 0.2 to 4 times the inner width of the sampling portion 302 (e.g., the diameter of the sampling portion 302), for example, 0.2 to 1 times, 0.5 to 1.5 times, 1 to 2 times, 2 to 4 times the width, or any intermediate, smaller, or larger value or range. In some embodiments, when the sampling portion 302 includes an inner sharpening portion surrounding at least a portion of the distal opening, the cutter is located at a distance of 0 to 2 times the width of the sampling portion after the inner sharpening portion, for example, a distance of 0 to 1 times, 0.5 to 1 times the width, or any intermediate, smaller, or larger value after the inner sharpening portion. Alternatively or additionally, the sampling portion includes an outer sharpening portion surrounding at least a portion of the distal opening. In some embodiments, the inner and / or outer sharpening portions are configured to form a circular incision in the body tissue as the sampling portion is axially advanced into the body tissue.

[0111] According to some exemplary embodiments, an inner cutter (e.g., cutters 316 and 318) extends inward from the wall 320 into the inner cavity 306 toward the proximal end 312, forming a maximum angle 324 between the cutter and the wall 320. In some embodiments, the maximum angle value is in the range of 3 degrees to 90 degrees, for example, in the range of 5 degrees to 45 degrees, in the range of 10 degrees to 30 degrees, or any intermediate, smaller, or larger range.

[0112] According to some exemplary embodiments, the inner cutters (e.g., cutters 316 and 318) are flexible and configured to move between a first state (an extended state, in which the cutters extend into the inner cavity 306 at a maximum angle 324) and a second state (in which the cutters are substantially aligned with the wall, for example, at an angle 324 to the wall 320 of less than 5 degrees, such as less than 3 degrees, less than 2 degrees, or any intermediate, smaller, or larger angle). In some embodiments, the cutters (e.g., cutters 316 and 318) are partially cut-out portions of the wall 320, remaining coupled to the wall 320 in connecting regions (e.g., connecting regions 315 and 317).

[0113] According to some exemplary embodiments, the cutter (e.g., cutters 316 and 318) is integral with the wall 320 and is optionally formed of the same material as the wall 320. In some embodiments, the cutter (e.g., cutters 316 and 318) is thinner than the wall 320, and its maximum thickness is less than 0.8 times the wall thickness, for example less than 0.6 times, less than 0.5 times, less than 0.3 times, or any intermediate, smaller, or larger value. In some embodiments, the cutter (e.g., cutters 316 and 318) is formed of a hyperelastic material or a shape memory alloy material, such as Nitinol, CuAlNi, CuZnAl, Fe-Mn-Si, NiTiCu, CuSnZn, and TiPd. In some embodiments, the material forming the cutter and / or sampling portion is a biocompatible material. In some embodiments, the sampling portion 302 or the body 304 is also formed of a shape memory alloy, or of a different shape memory alloy or material than that used to form the cutters (e.g., cutters 316 and 318).

[0114] According to some exemplary embodiments, the cutter may optionally be resilient. In some embodiments, when the cutter is in a relaxed state, the cutter extends inward into the cavity 306 and is in an extended state. In some embodiments, when a force, such as a mechanical force, is applied to the cutter within the cavity 306 in a radial direction (e.g., toward the wall 320), the cutter is pushed against the wall 320, for example, as long as the mechanical force is applied to the cutter. In some embodiments, an axial force, such as a bending moment, applies a force to the cutter, thereby pushing the cutter in a radially outward direction. In some embodiments, when the application of the mechanical force ceases, the cutter returns to the relaxed extended state into the cavity 306. In some embodiments, the maximum angle 324 is obtained when the cutter is in a relaxed state.

[0115] According to some exemplary embodiments, a cutter (e.g., one or more cutters 316 and 318) is coupled to the wall 320 via at least one hinge or hinge portion. Optionally, the hinge portion is resilient and configured to allow the cutter to bend inward into the inner cavity 306 when the hinge portion is in a relaxed state.

[0116] Now for reference Figure 3b It illustrates one or more internal cutters substantially aligned with the wall of the sampling portion according to some exemplary embodiments of the invention; and references Figure 3c It illustrates one or more internal cutters that extend inward into the cavity of the sampling portion according to some exemplary embodiments of the present invention.

[0117] According to some exemplary embodiments, for example Figure 3b As shown, the at least one inner cutter (e.g., cutters 316 and 318) is configured to move into an opening in the wall 320. In some embodiments, when a mechanical force is applied to the cutter from inside the cavity 306, the at least one inner cutter moves into the wall and substantially aligns with it. In some embodiments, the force is applied to the cutter in a proximal and / or radial direction, pushing the cutter into the opening in the wall. Alternatively, the force pushes the cutter against the wall, for example, against the inner surface of the wall, optionally attaching the cutter to the inner surface of the wall.

[0118] For example, such as Figure 3b As shown, a tissue penetrator 340, located within the lumen 306 and extending through a distal opening 314, is used to penetrate a more rigid and / or elastic portion of the tissue wall when advancing a sampling portion into target soft tissue of the body. In some embodiments, when the tissue penetrator 340 is located within the lumen 306, it applies a mechanical force to the at least one cutter (e.g., cutters 316 and 318) to at least partially push the cutter into the wall. Alternatively, the tissue penetrator pushes the cutter against the wall. In some embodiments, similarly, when body tissue enters the lumen 306 through the distal opening, it applies a force to the cutter to at least partially push the cutter into or against the wall.

[0119] According to some exemplary embodiments, for example Figure 3c As shown, when no force is applied from inside the cavity 306 to the cutter (e.g., cutters 316 and 318), the cutter extends into the cavity 306, optionally extending at a maximum angle 324.

[0120] According to some exemplary embodiments, for example Figure 3cAs shown, a cutter (e.g., cutter 340) has a first end 342 coupled to or integrated into a wall 320, and a second end 344 located at a distance from the wall 320. In some embodiments, the second end 344 is configured to be located within the cavity 306 when the cutter 340 extends inward into the cavity 306, for example, when the cutter relaxes from deflection or is in a stationary state. In some embodiments, the cutter includes a cutting edge located in the region between the first end 342 and the second end 344. Optionally, the cutting edge is located at the second end 344.

[0121] According to some exemplary embodiments, for example Figure 3d As shown, two or more cutters (e.g., cutters 346 and 348) are coupled to wall 320, for example, to the circumference of the wall. In some embodiments, cutters 346 and 348 are coupled to the wall at relative positions on the wall circumference. In some embodiments, each cutter 346 and 348 extends inward into cavity 306, and is oriented such that the distal end of each cutter points towards the proximal end of the sampling portion. In some embodiments, each cutter is oriented at a similar angle relative to wall 320.

[0122] According to some exemplary embodiments, for example Figure 3e As shown, the cutters (e.g., cutters 346 and 348) are oriented such that at least some or all of the cut edges of cutters 346 and 348 have the same axial position relative to the long axis of the sampling portion, for example, to allow the formation of a single cutting plane 350 in the tissue contacting the cut edges. In some embodiments, cutters 346 and 348 form the cutting plane 350 when the sampling portion and cutters 346 and 348 rotate about the long axis of the sampling portion body, and optionally in the absence of axial movement of the sampling portion and cutters 346 and 348.

[0123] A potential advantage of having a single cutting plane 350 is that it can separate proximal and distal tissue samples, with the proximal tissue sample continuing to flow within the sampling section lumen and continuing to connect to the organ tissue. If the cutter is not located in a similar axial position within the sampling section, tissue may be trapped by the cutter after the tissue sample is separated, thus blocking tissue from entering the sampling section.

[0124] Exemplary biopsy device According to some exemplary embodiments, a biopsy device includes a sampling portion having an internal cutter (e.g., a flexible internal cutter), the biopsy device being configured to remove tissue samples, such as biopsy samples, from soft tissue. In some embodiments, the soft tissue includes tissue suspected of containing a tumor, and the device is configured to remove at least one sample from the suspected tissue. In some embodiments, the device cuts the tissue sample by rotating and axially advancing the sampling portion (e.g., a needle) located at a distal end of the device into the tissue (e.g., soft tissue). In some embodiments, the device rotates the sampling portion in opposite directions to allow the tissue sample to separate from the tissue within the sampling portion, and / or to allow the separation of successive tissue samples from the tissue after each tissue sampling without having to completely pull the device out of the tissue.

[0125] Now for reference Figure 3f It describes a biopsy apparatus, also referred to herein as a biopsy system, according to some exemplary embodiments of the present invention.

[0126] According to some exemplary embodiments, a biopsy device (e.g., device 350) includes a control unit 352 and a sampling portion 354 (e.g., a needle), the sampling portion 354 being mechanically coupled to the control unit 352 via an elongated flexible shaft 356. In some embodiments, the flexible shaft 356 is a torque coil, such as a braided torque coil configured to axially advance and rotate the sampling portion 354 in different directions. In some embodiments, the flexible shaft is formed of interwoven strands of yarn, optionally in a helical shape.

[0127] According to some exemplary embodiments, the control unit 352 includes a control circuit 356 functionally coupled to at least one actuator 358. In some embodiments, the at least one actuator includes a motor, such as an electric motor. Alternatively or additionally, the at least one actuator includes a hydraulic or pneumatic actuator. In some embodiments, a shaft 356 is functionally coupled to the at least one actuator 358.

[0128] According to some exemplary embodiments, the control unit 352 includes a memory circuit 360 that stores one or more motion parameters of the sampling portion, such as axial advance speed, rotational tangential speed, the ratio between axial speed and tangential speed, rotation direction, axial advance direction and / or the duration of motion of the sampling portion.

[0129] According to some exemplary embodiments, the control unit 352 includes a user interface 362 configured to generate human-detectable instructions and / or receive input data from a user of the device 350 (e.g., a doctor, surgeon, specialist, or technician). In some embodiments, the input data includes one or more motion parameters stored in the memory 360.

[0130] According to some exemplary embodiments, during the tissue sampling process, for example Figure 4 as well as Figures 5d to 5g In the process described herein, the control circuit 356 is configured to signal the actuator 358 to rotate and / or axially advance the shaft 356 and the sampling portion 354 according to the motion parameters stored in the memory 360.

[0131] According to some exemplary embodiments, for example Figure 4 Frame 410 and Figure 5d and Figure 5e The control circuit 356 sends a signal to the actuator to axially advance the shaft 356 and the sampling portion 354 located at the distal end of the shaft 356. Furthermore, the control circuit 356 sends a signal to the actuator 358 to move along a first direction (e.g., Figure 7d The rotation axis 356 and sampling portion 354 (shown in direction 754) are rotated simultaneously and optionally synchronized with axial advance. In some embodiments, during axial advance and rotation, tissue enters the cavity 366 of the sampling portion 354 via the distal opening 354. In some embodiments, the tissue entering the cavity pushes an internal cutter, such as a cutter 368, against the wall 370 of the sampling portion.

[0132] According to some exemplary embodiments, similarly Figure 4 As described in block 416, after the tissue is introduced into the lumen 366 to a position proximal to the cutter 368, the control circuit 356 signals the actuator 358 to stop the axial advancement of the shaft 356 and the sampling portion 370. Furthermore, in some embodiments, the control circuit 356 signals the actuator 358 to stop the rotation of the shaft and the sampling portion along a first direction.

[0133] According to some exemplary embodiments, after a predetermined time period, the control circuit sends a signal to the actuator 358 to move in a second direction opposite to the first direction (e.g., ...). Figure 7d The direction shown is 746) for rotating the axis 356 and the sampling portion. In some embodiments, the control circuit signals the actuator to rotate the axis 356 and the sampling portion 354 along the second direction for a predetermined time period and / or at different rotation angles and / or a selected number of rotations. Optionally, during and / or after rotation along the second direction, the control circuit 356 signals the actuator 358 to retract the axis and the sampling portion, optionally retracting a predetermined distance, such as in predetermined steps. In some embodiments, the retraction of the sampling portion is performed after the rotation of the sampling portion. In some embodiments, the retraction of the sampling portion allows for the separation of a tissue sample from the tissue within the lumen 366, for example... Figure 5gAs shown. In some embodiments, retraction is manual, while axial forward advance and / or rotation are motor-driven. In some embodiments, after tissue separation, control circuit 356 signals the actuator to repeat the following sequence: (1) rotating in a first direction while advancing axially, (2) stopping axial advance, (3) rotating in a second direction, and (4) retracting the sampling portion, and optionally repeating to obtain additional tissue samples.

[0134] Exemplary detailed organization sampling process According to some exemplary embodiments, a tissue sampling device (e.g., a biopsy device) is used to obtain long, continuous samples of soft tissue from the body, such as tissue from the pancreas, liver, lymph nodes, spleen, lungs, glands, adrenal glands, kidneys, esophageal wall, stomach wall, or gastrointestinal organs. In some embodiments, the biopsy device is used to cut and separate long tissue samples from the body tissue, having a length of at least 1 mm, such as at least 2 mm, at least 3 mm, at least 4 mm, at least 5 mm, at least 6 mm, at least 7 mm, at least 8 mm, or any intermediate, smaller, or larger tissue sample length. Optionally, the biopsy device is used to obtain multiple separated long tissue samples during a single pass through the body tissue, and optionally, it is not necessary to retract the device from the body tissue. In some embodiments, the tissue sample includes suspected cancerous tissue, tumor tissue, or tissue blocks.

[0135] Now for reference Figure 4 It depicts a flowchart of a sampling process according to some exemplary embodiments of the present invention.

[0136] According to some exemplary embodiments, at block 402, the biopsy device is advanced toward the target tissue. In some embodiments, the biopsy device includes a flexible shaft with a distal sampling portion, such as a hollow needle, at its distal end. In some embodiments, the biopsy device includes an elongated tissue penetrator, such as the tissue penetrator described in International Patent Application Publication No. WO2022003691A1, which is incorporated herein by reference in its entirety. In some embodiments, the elongated tissue penetrator passes through the lumen of the shaft and the sampling portion and extends through a distal opening of the sampling portion.

[0137] According to some exemplary embodiments, the biopsy device is advanced, for example, within the working channel of an endoscope, toward the wall of the tissue.

[0138] According to some exemplary embodiments, at block 404, the biopsy device may optionally penetrate through the wall using a tissue penetrator. In some embodiments, the distal end of the biopsy device penetrates through the tissue wall using a tissue penetrator extending distal to the distal end of the biopsy device.

[0139] According to some exemplary embodiments, at block 406, after penetrating through the tissue wall, the tissue penetrator is retracted from the sampling portion lumen.

[0140] According to some exemplary embodiments, at block 408, the retraction of the tissue penetrator allows one or more internal cutters to bend inward from the wall of the sampling portion.

[0141] It should be noted that in some embodiments, there is no tissue penetrator within the lumen of the biopsy device or the sampling portion lumen, and one or more internal cutters have already bent inward from the wall into the lumen during advancement of the biopsy device. In some embodiments, when navigating to target tissue requiring sampling via the gastrointestinal tract or trachea, it is not necessary to penetrate the tissue wall to reach the target tissue; therefore, when extending distal to the sampling portion, a tissue penetrator is not required within the sampling portion lumen. In these embodiments where a tissue penetrator is not required, Figure 4 The process shown does not include boxes 404, 406 and / or 408.

[0142] According to some exemplary embodiments, at block 410, the sampling portion is axially advanced into the tissue while rotating. As used herein, rotation of the sampling portion refers to causing the sampling portion to rotate about its central long axis, optionally in a circular motion. In some embodiments, the sampling portion rotates at a tangential velocity in the range of 2.5 to 1000 mm / sec, such as 2.5 to 40 mm / sec, 30 to 40 mm / sec, 35 to 45 mm / sec, 30 to 50 mm / sec, 10 to 100 mm / sec, 50 to 500 mm / sec, 300 to 1000 mm / sec, or any intermediate, smaller, or larger range. Furthermore, during rotation, the sampling portion is axially advanced into the tissue at an axial velocity in the range of 1 to 100 mm / sec, such as 1 to 10 mm / sec, 5 to 12 mm / sec, 5 to 15 mm / sec, 5 to 50 mm / sec, 10 to 100 mm / sec, or any intermediate, smaller, or larger range. In some embodiments, the ratio between the tangential rotational speed and the axial speed is between 1 and 10, for example between 3.5 and 4.5, for example between 2 and 5, or any intermediate, smaller, or larger range of values. In some embodiments, this ratio is constant during the advancement of the sampling portion into the tissue. An example of advancing the sampling portion into the tissue is provided in WO2019155472A1, which is incorporated herein by reference in its entirety. In some embodiments, at block 410, the sampling portion is rotated and axially advanced into the tissue in a direction such that the distal end of a tissue manipulator (e.g., a cutter) coupled to the wall becomes the guide end initially facing the tissue entering the lumen of the sampling portion.

[0143] According to some exemplary embodiments, at block 412, during the advance of the sampling portion into the tissue, the tissue enters the lumen of the sampling portion through the distal opening of the sampling portion. In some embodiments, the tissue entering the lumen remains connected to tissue outside the sampling portion. Optionally, the tissue entering the lumen of the sampling portion is compressed because the width of the sampling portion's interior narrows relative to the width of the distal opening at the distal end of the cone. In some embodiments, during the entry of tissue into the lumen, the entering tissue pushes, for example, outwardly, the cutter toward the wall of the sampling portion.

[0144] According to some exemplary embodiments, at block 414, as the tissue advances proximally within the lumen, the tissue moves to the proximal side of the cutter.

[0145] According to some exemplary embodiments, at frame 416, the advancement of the sampling portion into the tissue is stopped. In some embodiments, axial advancement and rotation of the sampling portion are stopped at frame 416.

[0146] According to some exemplary embodiments, at block 418, the inner cutter bends inward to enter the tissue within the sampling portion lumen. In some embodiments, the bend of the cutter into the tissue within the lumen increases the contact and / or friction between at least one cutting edge of each cutter and the tissue within the lumen.

[0147] According to some exemplary embodiments, at block 420, the sampling portion rotates about its central long axis in the opposite direction to that used when the sampling portion is advanced into the tissue at block 410. For example, rotation in one direction causes the proximal free end of the tissue manipulator to face the tissue as a leading edge during rotation. In some embodiments, rotating the tissue manipulator at block 420 pushes the proximal free ends of one or more tissue manipulators into the tissue.

[0148] According to some exemplary embodiments, at frame 422, tissue within the lumen is cut by a tissue manipulator, such as a cutter. In some embodiments, when the sampling portion rotates at frame 420, at least one edge of the cutter, such as a cutting edge at the free proximal end, penetrates into the tissue, forming a circular incision, optionally a circumferential incision or groove, within the tissue. As an alternative to or supplement to the rotation of the sampling portion, the sampling portion is retracted while the cutter is within the tissue.

[0149] According to some exemplary embodiments, at frame 424, a tissue sample is separated from the tissue within the lumen of the sampling portion. In some embodiments, the tissue sample is separated from the tissue within the sampling portion at a cutting plane formed by the cutter at frame 422. In some embodiments, rotation of the sampling portion during cutting at frame 422 applies a force, such as a cutting force, tearing force, and / or shearing force, at the cutting plane, for example, at a plane between tissue distal to and proximal to the cutting plane, causing the proximal tissue (now the tissue sample) to separate from the tissue distal to the cutting plane that remains coupled to the tissue outside the sampling portion. In some embodiments, the cutting location is at the separation region formed by the cutter. Additionally or alternatively, the tissue sample is separated from the tissue within the sampling portion by tearing, for example by retracting the sampling portion after or during the incision at frame 422. Optionally, once the tissue sample has been separated, at frame 410, the sampling portion is rotated and further axially advanced into the tissue, for example, to obtain at least one additional sample.

[0150] Alternatively or additionally, with or without rotation, the retractable sampling section may tear or separate the tissue sample from the remaining tissue within the sampling section.

[0151] According to some exemplary embodiments, at block 426, a tissue sample is removed from the lumen of the sampling portion. In some embodiments, the tissue sample is removed from the distal opening, for example, by inserting an additional tube (e.g., a thin-walled tube) through the distal opening into the lumen of the sampling portion and pushing a cutter against or against the wall of the sampling portion. Alternatively, the tissue sample is removed from the proximal opening of the sampling portion, for example, after the sampling portion has disengaged from the flexible shaft. Alternatively, the tissue sample is removed by cutting the sampling portion (e.g., a sampling needle) to extract the tissue sample. Alternatively, the tissue sample is flushed out of the lumen of the sampling portion by introducing fluid (e.g., liquid or air), for example, through the distal or proximal opening. Alternatively, the tissue sample is removed from the lumen of the sampling portion by applying a vacuum to the lumen via the distal or proximal opening. Alternatively, the tissue sample is removed from the lumen of the sampling portion by introducing an elongated pusher element configured to push the sample out of the lumen through the distal or proximal opening.

[0152] Exemplary organization sampling Now for reference Figures 5a-5f It describes the process of tissue sampling using a biopsy device having a distal sampling portion (e.g., a needle) with at least one internal cutter according to some exemplary embodiments of the present invention.

[0153] According to some exemplary embodiments, for example Figure 5aAs shown, the sampling portion 502 is advanced toward a target tissue 504 (e.g., soft tissue) having a tissue wall 506 that at least partially surrounds the target tissue 504. In some embodiments, a tissue penetrator 508 is located within the lumen 510 of the sampling portion and extends through a distal opening of the sampling portion 502. In some embodiments, a biopsy device including the sampling portion 502 and the tissue penetrator 508 is axially advanced toward the target tissue 504 within the working channel of an endoscope.

[0154] According to some exemplary embodiments, Figure 5a The axial advancement of the biopsy device is manual, for example, by manually pushing the biopsy device toward the target tissue 504. Alternatively, Figure 5a The movement of the biopsy device is motor-driven and optionally performed in steps. In some embodiments, the axial advancement of the biopsy device may or may not include rotation of the sampling portion of the biopsy device. In some embodiments, the length of each step is predetermined and optionally equal. Alternatively, the length of each step is determined based on the distance between the biopsy device and the target tissue or target tissue wall. For example, the step length becomes shorter as the biopsy device gets closer to the target tissue or target tissue wall. In some embodiments, the advancement of the biopsy device, such as the sampling portion of the biopsy device, toward the target tissue is monitored using image processing based on one or more imaging modalities, such as ultrasound imaging.

[0155] According to some exemplary embodiments, in Figure 5a In this configuration, when the tissue penetrator 508 is located within the lumen 510, the at least one cutter, such as cutters 512 and 514, is at least partially attached to the wall 516, for example, to the inner surface of the wall 516. Alternatively, in Figure 5a In this context, the at least one cutter is located at least partially within the opening of wall 516.

[0156] According to some exemplary embodiments, for example Figure 5b As shown, the biopsy device uses a tissue penetrator 508 to penetrate through the wall 506. In some embodiments, during penetration, the tissue penetrator forms a fine incision in the tissue wall, as described in, for example, WO2022003691A1, which is incorporated herein by reference in its entirety.

[0157] According to some exemplary embodiments, for example Figure 5c As shown, after penetrating through wall 506, the tissue penetrator 508 is removed from the cavity 510 of the sampling portion 502. In some embodiments, after removal of the tissue penetrator, the at least one cutter, such as cutters 512 and 514, bends inward into the cavity 510 while maintaining coupling with wall 516. In some embodiments, for example Figure 5c As shown, the distal end of the sampling portion, including the distal opening 520, faces the target tissue 504.

[0158] According to some exemplary embodiments, for example Figure 5d As shown, the sampling portion 502 is now axially advanced into the target tissue 504 while rotating about the central axis 522 of the sampling portion 502. In some embodiments, during axial advancement, a circumferential cut around the distal opening 520 cuts through the target tissue. In some embodiments, after the cut and during axial advancement, a portion of the target tissue enters the lumen 510 via the distal opening 520 while remaining coupled to tissue outside the sampling portion 502.

[0159] According to some exemplary embodiments, for example Figure 5e As shown, during the axial advancement of the sampling portion 502 into the tissue 504, the tissue entering the cavity 510 pushes the cutters 512 and 514 against the wall 516. In some embodiments, the cutters 512 and 514 are at least partially pushed into openings in the wall 516, wherein each cutter is at least partially pushed into a different opening in the wall 516. Alternatively, the cutters 512 and 514 are pushed against the inner surface of the wall 516. In some embodiments, during the advancement of the sampling portion 502 into the tissue 504, the tissue in the cavity 510 penetrates to the proximal side of the cutters 512 and 514.

[0160] According to some exemplary embodiments, for example Figure 5f As shown, after the tissue portion within the cavity 510 is located proximal to cutters 512 and 514, the axial advancement of sampling portion 502 into tissue 504 is stopped. Furthermore, rotation of the sampling portion is also stopped. In some embodiments, when advancement of tissue into the cavity 510 stops, the dynamic radial force exerted on cutters 512 and 514 along the wall 516 direction decreases, and cutters 512 and 514 bend inward into the cavity 510 and into the tissue within the cavity. In some embodiments, when the force exerted on cutters 512 and 514 by the tissue in the cavity 510 decreases, cutters 512 and 514 (e.g., flexible and optionally elastic cutters) are allowed to return to a relaxed state and bend into the cavity 510. In some embodiments, the cutters are elastically deflectable. In some embodiments, when the force exerted on the cutters by the tissue decreases, the cutters recover from deflection, and at least a portion of the cutters bend inward into the tissue.

[0161] According to some exemplary embodiments, when cutters 512 and 514 bend into the tissue, the cutting edge of each cutter contacts the tissue.

[0162] According to some exemplary embodiments, for example Figure 5g As shown, after the cutter bends into the tissue within the cavity, the sampling portion is rotated. In some embodiments, the sampling portion rotates in the same direction as the rotation applied during axial advancement into the tissue (e.g., ...). Figure 5d and Figure 5e (as shown) rotates in the opposite direction. In some embodiments, rotation of the sampling portion causes the cutter to move around the tissue in the lumen, forming a circumferential incision or groove in the tissue, optionally in a single cutting plane. In some embodiments, the sampling portion retracts from the tissue during and / or after rotation. In some embodiments, retraction of the sampling portion applies tearing and / or torsional and / or shearing forces to the tissue in the lumen at a single cutting plane, such as applying force to the tissue at the formed separation region, causing the tissue sample (e.g., tissue sample 530) located proximal to the cutting plane to separate from the tissue in the lumen located distal to the cutting plane (e.g., between the cutting plane and the distal opening of the sampling portion).

[0163] According to some exemplary embodiments, for example Figure 5g As shown, when the sampling portion 502 retracts, the inwardly bent cutters 512 and 514 prevent the tissue sample 530 from moving to the distal side of the cutters 512 and 514, thus acting as a one-way valve.

[0164] According to some exemplary embodiments, for example Figure 5h As shown, repeat, for example Figure 5e-5g The actions shown allow for the separation of multiple tissue samples, such as tissue samples 530, 532, 534, and 536, without having to completely pull the sampled portion out of the organ, such as from tissue 504.

[0165] Exemplary tissue sample extraction According to some exemplary embodiments, one or more tissue samples located within the sampling portion are extracted at the end of the tissue sampling procedure. In some embodiments, the one or more tissue samples are extracted from the sampling portion when it is removed from the patient.

[0166] According to some exemplary embodiments, the cutter is removed from the sampling portion lumen, or pushed against or into the sampling portion wall. In some embodiments, the cutter changes orientation between a flexible state and a stable non-flexible plastic state based on a plastic-to-elastic transition temperature; for example, the cutter is elastic at body temperature and plastic at room temperature. In some embodiments, for example... Figure 6a As shown, the cutter opener 602 is pushed into the cavity 510 via the distal opening 520. In some embodiments, the cutter opener 602 pushes cutters 512 and 514 against the wall 516 or into the opening in the wall 516. In some embodiments, cutters 512 and 514 are held attached to or retained within the wall 516 by friction between the wall and each cutter, and / or by the cutter changing from an elastic configuration to a plastic configuration (e.g., based on the elastic-to-plastic transition temperature of the cutter).

[0167] According to some exemplary embodiments, when the cutters 512 and 514 remain attached to or retained within the wall 516, the tissue sample is moved to the distal opening 520 and removed from the distal opening 520 by applying a vacuum from the distal opening, or, for example... Figure 6b As shown, tissue samples 606 and 608 are pushed out of the lumen 510 via a pusher shaft 610 through a distal opening 520, wherein the pusher shaft is inserted into the lumen of the sampling portion through a proximal opening of the sampling portion. Alternatively, the one or more tissue samples can be flushed out using fluid.

[0168] According to some exemplary embodiments, for example Figure 6c As shown, a tissue extraction tube, such as tube 612, is pushed through the distal opening 520 and pushes cutters 512 and 514 against wall 516. In some embodiments, for example... Figure 6d As shown, pusher shaft 610 pushes tissue samples 606 and 608 into tube 612 and pushes them out from the sampling section.

[0169] According to some exemplary embodiments, the tissue extraction tube 612 has a beveled tip, for example, to allow the tube 612 to be easily inserted into the sampling portion 502 via the distal opening 520.

[0170] According to some exemplary embodiments, for example Figure 6e As shown, the sampling portion 502, such as a sampling needle, is coupled to the flexible shaft 620. In some embodiments, the flexible shaft is configured to transmit rotational and / or axial forces from at least one motor of the biopsy device and the sampling portion 502. In some embodiments, the flexible shaft is flexible enough to transmit rotational and / or axial movement when the shaft is at least partially located within the working channel of the endoscope, such as within the working channel of a flexible endoscope.

[0171] According to some exemplary embodiments, the shaft 620 is coupled to the sampling portion 502 via at least one connector 622, such as a snap-fit ​​connector or a bayonet connector. In some embodiments, the connector is a circumferential connector. In some embodiments, in order to extract tissue samples 606 and 608 from the lumen of the sampling portion, the sampling portion 502 is released from the shaft 620, for example by releasing the sampling portion 502 and / or the shaft 620 from the connector 622, such as... Figure 6f As shown, or by cutting the sampling portion 502. In some embodiments, when the sampling portion 502 is disengaged from the shaft 620, the proximal opening 624 of the sampling portion 502 allows access to the lumen 510 and / or to tissue samples 606 and 608. In some embodiments, for example Figure 5gAs shown, the pusher shaft 630 is inserted into the cavity 510 through the distal opening 520, pushing the cutters 512 and 514 against the wall 516, and pushing tissue samples, such as samples 606 and 608, from the cavity 510 through the proximal opening 624 out of the sampling portion 502.

[0172] Alternatively, a fluid (e.g., saline) may be injected through the distal opening 520 to flush samples (e.g., samples 606 and 608) from the sampling portion 502 through the proximal opening 624, and / or through the proximal opening of the shaft coupled to the sampling portion or through the proximal opening of the handle coupled to the shaft.

[0173] Alternatively, a vacuum can be applied to remove tissue through an opening at the proximal end of the sampling section or biopsy device, or tissue can be removed by pushing a shaft or tube into the lumen and toward the proximal end.

[0174] Exemplary biopsy device sampling section and internal cutter According to some exemplary embodiments, each cutter, such as each flexible or resilient cutter, is part of the sampling portion wall, cutting out from the wall portion. Now refer to Figures 7a-7e It depicts one or more cutters as a partial cutting portion of a biopsy device sampling portion according to some exemplary embodiments of the present invention.

[0175] According to some exemplary embodiments, for example Figure 7a As shown, the sampling portion 702 of the biopsy device includes an elongated body 704 having a distal end 706 and a proximal end 708. In some embodiments, the body is a hollow body having an inner cavity extending between the distal end 706 and the proximal end 708. In some embodiments, the body 704 is tubular. In some embodiments, the inner cavity of the body 704 includes a distal opening 710 at the distal end 706.

[0176] According to some exemplary embodiments, for example, also in Figure 7b ( Figure 7a As shown in the enlarged view of region 712, distal end 706 is a flat and straight distal end. In some embodiments, sampling portion 702 includes at least one tissue manipulator, such as at least one cutter 714, which may optionally be flexible or elastically deflectable. In some embodiments, cutter 714 is a cut-out portion of a wall of the body (e.g., wall 716). In some embodiments, an arcuate incision, such as a U-shaped incision 718, is formed in wall 716 at a distance 720 from distal end 706. In some embodiments, the value of distance 720 is in the range of 0.5 mm to 10 mm, for example, in the range of 0.5 mm to 3 mm, in the range of 1 mm to 5 mm, or any intermediate, smaller, or larger range.

[0177] According to some exemplary embodiments, a cutter 714 is formed, and the major axis 717 of the cutter 714 is oriented at an angle 719 relative to the transverse axis 720 of the body 704, for example, the transverse axis 720 being an axis perpendicular to the major axis 722 of the body 704. In some embodiments, the value of angle 719 is in the range of 5 degrees to 20 degrees, for example, in the range of 5 degrees to 12 degrees, in the range of 8 degrees to 15 degrees, in the range of 10 degrees to 14.5 degrees, in the range of 12 degrees to 14.5 degrees, or any intermediate, smaller, or larger range of values.

[0178] According to some exemplary embodiments, the value of angle 719 (α) depends on and / or is determined based on the ratio between the axial velocity and the tangential velocity of the sampling portion, for example, according to the following calculation: D = Diameter of the main body of the sampling portion ω = Rotational speed (revolutions per second) π x D = circumference V_tangential = ω x π x D α = tan -1 (V-axis / V-tangential) For example: when ω = 13 revolutions / second, V-axis = 9 mm / sec and D = 1 mm, then V-tangential = π x 1 x 13 = 40.84, and angle α = tan -1 (0.22) = 12.4 degrees.

[0179] According to some exemplary embodiments, for example Figure 7c As shown (a transparent view of sampling portion 702), the sampling portion includes two spaced-apart cutters 714 and 730, which are partial cutouts from the wall 716. In some embodiments, each cutter, such as a flexible and optionally resilient cutter, is formed by creating a U-shaped cut through the wall. In some embodiments, the cutters are located on opposite sides of the wall. In some embodiments, the cutters are aligned in the same direction.

[0180] According to some exemplary embodiments, such as Figure 7c As shown, the distal end 706 is a tapered end surrounding the distal opening 710. In some embodiments, the distal end has an inner sharpened edge and / or an outer sharpened edge, for example to allow the distal end to cut through the tissue as it is axially advanced into the tissue, for example... Figure 5d and Figure 5e As shown. In some embodiments, as Figure 7cThe maximum internal width 740 of the sampling portion at the distal end 706, such as the inner diameter, is in the range of 0.4 to 10 mm, for example, 0.4 to 5 mm, 0.5 to 2 mm, 0.5 to 3 mm, 1 to 5 mm, 3 to 10 mm, or any intermediate, smaller, or larger value. In some embodiments, the minimum internal width 742 of the sampling portion at the narrow portion, such as the inner diameter, is in the range of 0.5 to 8 mm, for example, 0.5 to 2 mm, 1 to 2 mm, 1.5 to 5 mm, 2 to 8 mm, or any intermediate, smaller, or larger value. In some embodiments, the maximum thickness 744 of the wall 716 is in the range of 0.04 to 2 mm, for example, 0.04 to 1 mm, 0.05 to 0.1 mm, 0.05 to 0.2 mm, 0.1 to 2 mm, or any intermediate, smaller, or larger value.

[0181] Now for reference Figure 7d and Figure 7e It depicts a cutter arrangement along the circumference of the sampling portion of a biopsy device according to some exemplary embodiments of the present invention.

[0182] According to some exemplary embodiments, for example Figure 7d and Figure 7e As shown, two cutters 714 and 730 are aligned along the same circumferential direction 746. In some embodiments, each cutter includes a distal end and a proximal free end 752, the distal end being, for example, a base region 750 coupled to (optionally integral with) the wall 716, and the proximal free end 752 being configured to lie within the lumen 729 of the sampling portion 702. In some embodiments, each cutter includes at least one cutting edge located between the base 750 and the proximal free end 752, and optionally at the proximal free end 752.

[0183] According to some exemplary embodiments, the distal end 750 of the tissue manipulator is closer to the distal end and / or distal opening of the sampling portion than the proximal end 752 of the tissue manipulator. In some embodiments, the radius of curvature of the tissue manipulator between the distal end 750 and the proximal end 752 is approximately the radius of curvature of the sampling portion wall. Alternatively, the radius of curvature of the tissue manipulator is at most 50% smaller or larger than the radius of curvature of the sampling portion wall, for example, at most 40%, at most 30%, at most 15%, or any intermediate, smaller, or larger percentage value. Alternatively, the tissue manipulator between the distal end 750 and the proximal end 752 is straight.

[0184] According to some exemplary embodiments, during the axial advancement of the sampling portion into the tissue, for example... Figure 5d and Figure 5eAs shown, the sampling portion rotates in direction 754, in which the base 750 serves as the guide end of the cutter during rotation. In some embodiments, during axial advancement into the tissue, the tissue entering the lumen of the sampling portion pushes each cutter toward and optionally into an opening in the wall; for example, cutter 714 is pushed toward and optionally into... Figure 7b The opening 718 is shown. In some embodiments, rotation along direction 754 pushes each cutter at least partially into the opening in the wall.

[0185] According to some exemplary embodiments, in order to cut the tissue within the sampling lumen, for example... Figure 5g As shown, the sampling portion rotates in direction 746, which is opposite to direction 754, so that the distal end 752 becomes the guide end of the cutter, cutting through the tissue.

[0186] Now for reference Figure 8a It shows a tubular body of a sampling portion in the form of an unfolded plane according to some exemplary embodiments of the present invention.

[0187] According to some exemplary embodiments, each cutter, such as cutters 802 and 804, is formed and positioned at a distance 806 from the distal end 808 of the sampling portion body. In some embodiments, the value of distance 806 is in the range of 0.1 to 15 mm from the distal end of the sampling portion, for example, 0.1 to 5 mm, 1 to 4 mm, 2 to 10 mm, or any intermediate, smaller, or larger range. In some embodiments, if the sampling portion includes an inner sharpened region or an outer sharpened region that at least partially surrounds the distal opening, the distance between the cutter and the inner sharpened region is in the range of 0 to 2 mm, for example, 0 to 1 mm, 0.1 to 1.5 mm, or any intermediate, smaller, or larger range. In some embodiments, for example... Figure 8a As shown, cutters 802 and 804 have the same axial position on the body 810. In some embodiments, each cutter 802 and 804 is formed by cutting an arcuate slit, such as a U-shaped slit, on the wall 816, for example, slits 812 and 814 respectively. In some embodiments, the slit (e.g., a laser slit) has a width 825 in the range of 0.005 to 0.05 mm, for example, in the range of 0.01 to 0.05 mm, in the range of 0.015 to 0.03 mm, or any intermediate, smaller, or larger range of values.

[0188] Now for reference Figure 8b This is according to some exemplary embodiments of the present invention. Figure 8a The enlarged view of part 820 is shown.

[0189] According to some exemplary embodiments, each cutter, such as cutter 802, is oriented at an angle 822 (e.g., angle α calculated above) relative to the transverse axis 824 of the sampling portion body. In some embodiments, angle 822 is in the range of 5 degrees to 20 degrees, for example, in the range of 5 degrees to 12 degrees, in the range of 8 degrees to 15 degrees, in the range of 10 degrees to 14.5 degrees, in the range of 12 degrees to 14.5 degrees, or any intermediate, smaller, or larger range. In some embodiments, as described above, angle 822 is determined based on the ratio between the axial advance velocity and the tangential velocity of the sampling portion.

[0190] According to some exemplary embodiments, the length 826 between the base 828 and the end 830 of each cutter is in the range of 0.4 mm to 8 mm, for example, in the range of 0.4 mm to 3 mm, in the range of 1 mm to 5 mm, or any intermediate, smaller, or larger range. In some embodiments, this length is based on the number of cutters and determined according to the circumference: Length 826 = circumference [1 / (2 x number of cutters)]. For example, for 2 cutters, length 826 is 1 / 4 of the circumference.

[0191] In some embodiments, the width 832 of the base region 828 to which each cutter is coupled to the wall is in the range of 0.2 mm to 2 mm, for example, in the range of 0.5 mm to 1 mm, in the range of 1 mm to 2 mm, or any intermediate, smaller, or larger range. In some embodiments, the width 832 is approximately one-third of the length 826.

[0192] It is anticipated that many related sampling needles will be developed during the mature patent term of this application; the scope of the term "sampling" is intended to a priori include all such new technologies.

[0193] In this article, the term “about” as used for quantities or values ​​means “within ±10%”.

[0194] The terms “including,” “comprising,” “having,” and their variations mean “including but not limited to.”

[0195] The term "composed of" means "including and limited to".

[0196] The term "consistently of" means that the composition, method, or structure may include additional ingredients, steps, and / or portions, provided that such additional ingredients, steps, and / or portions do not materially alter the fundamental and novel characteristics of the claimed composition, method, or structure.

[0197] As used herein, unless the context clearly specifies otherwise, the singular forms “a,” “an,” and “the” include plural references. For example, the terms “a compound” or “at least one compound” can include a variety of compounds, including mixtures thereof.

[0198] Throughout this application, embodiments of the invention may be presented with reference to a scope format. It should be understood that the scope format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the invention. Therefore, a scope description should be considered as specifically disclosing all possible sub-scopes and the individual numerical values ​​within those scopes. For example, a description of a scope such as "from 1 to 6" should be considered as specifically disclosing sub-scopes such as "from 1 to 3", "from 1 to 4", "from 1 to 5", "from 2 to 4", "from 2 to 6", "from 3 to 6", etc.; and the individual numbers within that scope, such as 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the scope.

[0199] Whenever a range of numbers is indicated herein (e.g., “10-15”, “10 to 15”, or any pair of numbers connected by these or other such range indicators), any number (fraction or integer) within the indicated range boundaries is intended to be included, including the range boundaries, unless the context explicitly specifies otherwise. The phrases “range between the first indicated number” and “second indicated number” and “range from the first indicated number to,” “until,” “until,” or “to” (or other such range indicator terms) are used interchangeably herein and are intended to include the first and second indicated numbers and all fractions and integers between them.

[0200] Unless otherwise stated, the figures used herein, and any ranges of figures based thereon, are approximations within the range of reasonable measurement accuracy and rounding error as understood by those skilled in the art.

[0201] It should be understood that certain features of the invention described in the context of separate embodiments for clarity may also be provided in combination in a single embodiment. Conversely, various features of the invention described in the context of a single embodiment for brevity may also be provided separately or in any suitable sub-combination, or in any other described embodiment of the invention. Certain features described in the context of various embodiments should not be considered essential features of those embodiments unless the embodiment would not function without these elements.

[0202] Although the invention has been described in conjunction with specific embodiments thereof, it will be apparent to those skilled in the art that many alternatives, modifications, and variations will be readily apparent. Therefore, it is intended to cover all such alternatives, modifications, and variations falling within the spirit and broad scope of the appended claims.

[0203] The applicant intends to incorporate, in its entirety, all publications, patents, and patent applications referenced herein by reference, as if each individual publication, patent, or patent application were specifically and individually indicated to be incorporated herein by reference. Furthermore, any reference or designation of any reference in this application should not be construed as an admission that such reference is prior art to the invention. The use of partial headings should not be construed as a necessary limitation. In addition, any priority documents of this application are hereby incorporated herein by reference in their entirety.

Claims

1. A biopsy device, comprising: The hollow sampling portion includes an elongated body having a long axis, a proximal end, a distal end, and an inner cavity located within the body and disposed along the long axis. The distal end of the sampling portion includes a distal opening whose shape and size are designed to allow tissue to enter the cavity when the hollow sampling portion is axially advanced into the body tissue. At least one movable tissue manipulator extends from the wall of the sampling portion body into the cavity and toward the proximal end of the sampling portion; The at least one tissue manipulator is configured to move outward toward the wall and inward toward the lumen.

2. The apparatus of claim 1, wherein the at least one movable tissue manipulator is shaped and sized to be pushed by the tissue entering the cavity against the inner surface of the wall of the sampling portion, and to be moved back toward the cavity and to apply force to the tissue in the cavity.

3. The apparatus of claim 1, wherein the at least one tissue manipulator is configured to retract toward the inner cavity when the axial advance of the hollow sampling portion stops.

4. The apparatus of claim 2, wherein the at least one tissue manipulator is an elastically deflectable tissue manipulator configured to be elastically deflected toward the inner wall surface by the tissue entering the cavity through the distal opening, and to recover from the deflection when the axial advancement of the hollow sampling portion into the body tissue stops.

5. The apparatus of claim 1, wherein the at least one tissue manipulator is a portion of the wall of the sampling section.

6. The apparatus of claim 5, wherein the at least one tissue manipulator is formed of the material of the wall.

7. The apparatus of claim 5, wherein the at least one tissue manipulator is formed by forming an arcuate incision across the wall, and wherein the width of the incision is between 0.005 mm and 0.05 mm.

8. The apparatus of claim 1, wherein the at least one tissue manipulator includes a distal end and a proximal end, the distal end being coupled to or integrally located with the wall near the distal end of the sampling portion, the proximal end being configured to be positioned within the lumen, and wherein the distal end of the at least one tissue manipulator is located at a distance between 0.1 mm and 20 mm from the distal end of the sampling portion, or at a distance of up to four times the internal width of the sampling portion from the distal end of the sampling portion.

9. The apparatus of claim 8, wherein the distal end of the at least one tissue manipulator is located at the level of and / or aligned with the wall of the hollow sampling portion.

10. The apparatus of claim 8, wherein the radius of curvature of the at least one tissue manipulator between the distal end and the proximal end is the radius of curvature of the wall of the hollow sampling portion.

11. The apparatus of claim 8, wherein the radius of curvature of the at least one tissue manipulator between the distal end and the proximal end is at most 30% smaller or larger than the radius of curvature of the wall of the hollow sampling portion.

12. The apparatus of claim 8, wherein the at least one tissue manipulator is straight between the distal end and the proximal end.

13. The apparatus of claim 1, wherein the tilt angle between the at least one tissue manipulator and the plane perpendicular to the long axis of the sampling portion is between 5 degrees and 30 degrees.

14. The device of claim 1, wherein the at least one tissue manipulator is formed of a superelastic and / or shape memory alloy.

15. The apparatus of claim 1, wherein the at least one tissue manipulator is configured to form a tissue separation region in the tissue by moving back toward the cavity and applying force to the tissue in the cavity, wherein the tissue separation region is a region that is easier to separate than other regions of the body tissue portion.

16. The apparatus of claim 1, wherein the at least one tissue manipulator is configured to form a tissue separation region in the tissue by moving back toward and penetrating into the lumen, wherein the tissue separation region is a region that is easier to separate than other regions of the body tissue portion.

17. The apparatus of claim 15, wherein when the hollow sampling portion is rotated and / or retracted, the hollow sampling portion applies a force to the tissue in the cavity, the force being sufficient to separate the tissue sample from the tissue at the tissue separation region.

18. The apparatus of claim 15, wherein the hollow sampling portion is axially advanced into the body tissue while rotating in a first direction, and wherein the at least one movable tissue manipulator is configured to form the tissue separation region when the axial advancement stops and when the hollow sampling portion rotates in the opposite second direction.

19. The apparatus of claim 15, wherein the at least one tissue manipulator includes a tissue-penetrating edge configured to contact tissue in the lumen and to form the separation region by forming at least a partially circumferential groove or at least a partially circumferential slit in the tissue as the hollow sampling portion rotates.

20. The apparatus of claim 1, wherein the at least one tissue manipulator comprises at least two tissue manipulators, each of the tissue manipulators having a tissue contact end configured to contact the tissue in the lumen, wherein when each of the at least two tissue manipulators is fully extended into the lumen, the tissue contact ends of the at least two tissue manipulators are located on a single plane substantially perpendicular to the long axis.

21. The apparatus of claim 1, comprising at least one actuator and a shaft having a distal end and a proximal end, wherein the at least one actuator is coupled to the proximal end of the shaft and the hollow sampling portion is coupled to the distal end of the shaft, and wherein the shaft is configured to rotate and / or axially advance the hollow sampling portion within the body tissue.

22. The apparatus of claim 21, wherein when the sampling portion is axially advanced into the body tissue, the shaft rotates the sampling portion in a first direction, and wherein rotating the sampling portion in the opposite second direction by the shaft forms a tissue separation region and / or separates the tissue sample from the tissue in the lumen.

23. The apparatus of claim 21, wherein the at least one actuator is configured to rotate the sampling portion at a tangential speed between 2.5 and 1000 mm / sec.

24. The apparatus of claim 21, wherein the at least one actuator is configured to axially advance the sampling portion at an axial velocity between 1 and 100 mm / sec.

25. The apparatus of claim 21, wherein the ratio between the axial velocity and the tangential velocity of the sampling portion is between 1 and 10.

26. The apparatus of claim 21, wherein the ratio between the axial velocity and the tangential velocity of the sampling portion is between 2 and 5.

27. The apparatus of claim 21, wherein the shaft is a flexible shaft.

28. The apparatus of claim 1, wherein the shape and size of the sampling portion are designed to advance toward the body tissue within the working channel of the endoscope.

29. The apparatus of claim 1, wherein the hollow sampling portion comprises a sampling needle.

30. The apparatus of claim 1, wherein the distal end of the sampling portion is substantially perpendicular to the long axis of the sampling portion.

31. The apparatus of claim 1, wherein the distal end of the sampling portion includes an inner sharpened edge and / or an outer sharpened edge, the edges surrounding the distal opening and configured to form a circular incision through the body tissue during axial advancement and / or rotation of the sampling portion into the body tissue.

32. A method for tissue sampling, comprising: The sampling portion of the biopsy device is axially advanced into the body tissue, wherein during the axial advancement, a portion of the body tissue enters the cavity of the sampling portion, and at least one tissue manipulator extending from the wall of the sampling portion into the cavity is pushed outward toward the wall; When the at least one tissue manipulator moves back into the cavity, force is applied to the body tissue portion by the at least one tissue manipulator; A tissue separation region is formed in the body tissue portion, wherein the tissue separation region is a region that is easier to separate than other regions of the body tissue portion in the cavity in response to the application of a separation force to the body tissue portion; By applying the separation force to the body tissue portion, the tissue sample is separated from the body tissue portion at the tissue separation region.

33. The method of claim 32, wherein the at least one tissue manipulator comprises two or more tissue manipulators, and wherein the application comprises grasping the body tissue portion in the cavity by the two or more tissue manipulators as the two or more tissue manipulators retract into the cavity.

34. The method of claim 32, wherein forming the tissue separation region by the at least one tissue manipulator comprises rotating the at least one tissue manipulator while applying the force to form at least a partially circumferential groove or slit in the body tissue portion.

35. The method of claim 34, further comprising rotating the sampling portion and the at least one tissue manipulator during the formation to form the at least partially circumferential groove or slit in the body tissue portion while the at least one tissue manipulator applies the force to the body tissue portion.

36. The method of claim 34, wherein the axial advancement comprises axial advancement while rotating the sampling portion relative to the body tissue in a first direction, and wherein the forming comprises forming the tissue separation region by rotating the sampling portion and the at least one tissue manipulator in the opposite second direction while applying the force to the body tissue portion via the at least one tissue manipulator.

37. The method of claim 32, further comprising stopping the axial advance before forming the tissue separation region.

38. The method of claim 32, wherein the separation comprises applying a shear force to the body tissue portion by rotating the sampling portion relative to the body tissue located outside the sampling portion to separate the tissue sample.

39. The method of claim 32, wherein the separation comprises separating the tissue sample by retracting the sampling portion from the body tissue and applying a tearing force to the body tissue portion.

40. The method of claim 32, further comprising repeating the axial advance, the application, the formation, and the separation to obtain at least one additional tissue sample from the body tissue.

41. The method of claim 32, wherein the axial advance comprises axially advancing the sampling portion into the body tissue at an axial velocity between 1 and 100 mm / sec.

42. The method of claim 41, wherein the axial advance comprises rotating the sampling portion at a tangential velocity between 2.5 and 1000 mm / sec during the axial advance.

43. The method of claim 42, wherein the ratio between the axial velocity and the tangential velocity is in the range of 3 to 5.

44. A soft tissue biopsy device, comprising: A slender handle, including gripping components; A slender, flexible shaft mechanically includes a hollow distal sampling portion having an inner cavity and a distal opening facing soft tissue; At least one drive unit is configured to rotate the sampling portion as it is axially advanced into the soft tissue, wherein the ratio between the tangential rotational speed and the axial advancement speed of the sampling portion is between 1 and 10.

45. The apparatus of claim 44, wherein the at least one drive unit rotates the elongated flexible shaft at a tangential speed in the range of 2.5 to 1000 mm / sec.

46. ​​The apparatus of claim 44, wherein the at least one drive unit axially advances the sampling portion at an axial velocity in the range of 1 to 100 mm / sec.

47. The apparatus of claim 44, wherein the distal opening is located at the distal end of the sampling portion, and wherein the distal end of the sampling portion is a flat, straight end or substantially perpendicular to the long axis of the sampling portion.

48. The apparatus of claim 44, wherein the ratio is between 2 and 5.

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