Abstract
The invention relates to a core biopsy needle (1) for obtaining a tissue sample comprising a hollow outer needle (10) extending along a longitudinal axis (L), and an inner needle (20), which is at least partially arranged or arrangeable within said outer needle along said longitudinal axis (L), wherein said inner needle (20) comprises at least one tissue-holding surface (21), wherein said tissue-holding surface (21) is adapted such that a tissue (3) adheres to the at least one tissue-holding surface (21), when the core biopsy needle (1) is inserted into the tissue (3).
Claims
1. A core biopsy needle (1) for obtaining a tissue sample comprising a hollow outer needle (10) extending along a longitudinal axis (L), an inner needle (20), which is at least partially arranged or arrangeable within said outer needle (10) along said longitudinal axis (L), characterized in that, said inner needle (20) comprises at least one tissue-holding surface (21), wherein said tissue-holding surface (21) is adapted such that a tissue (3) adheres to the at least one tissue-holding surface (21), when the core biopsy needle (1) is inserted into the tissue (3).
2. The core biopsy needle (1) according to claim 1, characterized in that said outer needle (10) comprises a maximum extension (e.sub.max) of less than 1.2 mm, particularly less than 1 mm, transversely to said longitudinal axis (L).
3. The core biopsy needle (1) according to claim 1, characterized in that said at least one tissue-holding surface (21) comprises a plurality of protrusions (40), each having a length (y) extending along said longitudinal axis (L), a width (x) extending in a circumferential direction in respect of said longitudinal axis (L), and a height (z) extending in a radial direction in respect of said longitudinal axis (L).
4. The core biopsy needle (1) according to claim 3, characterized in that the ratio between said width (x) and said length (y) of said protrusions (40) or the ratio between said length (y) and said width (x) of said protrusions (40) is at least 2 to 1.
5. The core biopsy needle (1) according to claim 3, characterized in that the ratio between said height (z) and said width (x) and/or the ratio between said height (z) and said length (y) of said protrusions (40) is at least 1 to 1.
6. The core biopsy needle (1) according to claim 3, characterized in that said height (z) is 1 m to 100 m, particularly 10 m to 80 m, more particularly 24 m to 40 m.
7. The core biopsy needle (1) according to claim 3, characterized in that said width (x) is 1 m to 100 m, particularly 10 m to 80 m, and/or said length (y) is 1 m to 100 m, particularly 10 m to 80 m.
8. The core biopsy needle (1) according to claim 3, characterized in that said protrusions (40) comprise respective peaks (41) positioned at a maximum height (z) of said respective protrusion (40).
9. The core biopsy needle (1) according to claim 3, characterized in that a surface of said protrusions (41) comprises a curvature (42), wherein particularly said surface is concave.
10. The core biopsy needle (1) according to claim 3, characterized in that said protrusions (40) are shaped as pyramids (43), particularly comprising a square-shaped base (44), or are shaped as cones, truncated cones or cylinders, particularly comprising a circular base, or comprise a triangular cross-sectional shape perpendicular to the width (x) and a rectangular or square-shaped cross-sectional shape perpendicular to the length (y), or comprise a triangular cross-sectional shape perpendicular to the length (y) and a rectangular or square-shaped cross-sectional shape perpendicular to the width (x) or comprise a cross-sectional shape perpendicular to the width (x) or the length (y), wherein said cross-sectional shape is delimited by at least three edges, wherein at least one of the edges is curved.
11. The core biopsy needle (1) according to claim 1, characterized in that said tissue-holding surface (21) comprises at least one tissue-adhesive compound which is adapted to adhere to said tissue by chemisorption and/or physisorption.
12. The core biopsy needle (1) according to claim 11, characterized in that said at least one tissue adhesive compound is a glue, particularly a silicon composite or cyanoacrylate.
13. The core biopsy needle (1) according to claim 11, characterized in that said at least one tissue-adhesive compound is bio-compatible.
14. The core biopsy needle (1) according to claim 11, characterized in that said at least one tissue-adhesive compound is a polymer or a biopolymer, particularly a peptide, polypeptide or protein, more particularly selected from the group consisting of arginine-glycine-aspartic acid tripeptides, poly-L-lysine, albumin, collagen I, fibrin, and gelatin.
15. The core biopsy needle (1) according to claim 11, characterized in that said at least one tissue-adhesive compound is a chemical cross-linker, wherein particularly said chemical cross-linker is an aldehyde, more particularly formaldehyde or glutaraldehyde.
16. The core biopsy needle (1) according to claim 3, characterized in that said tissue-holding surface (21) comprises at least one tissue-adhesive compound which is adapted to adhere to said tissue by chemisorption and/or physisorption.
17. The core biopsy needle (1) according to claim 16, characterized in that said at least one tissue adhesive compound is a glue, particularly a silicon composite or cyanoacrylate.
18. The core biopsy needle (1) according to claim 16, characterized in that said at least one tissue-adhesive compound is bio-compatible.
19. The core biopsy needle (1) according to claim 16, characterized in that said at least one tissue-adhesive compound is a polymer or a biopolymer, particularly a peptide, polypeptide or protein, more particularly selected from the group consisting of arginine-glycine-aspartic acid tripeptides, poly-L-lysine, albumin, collagen I, fibrin, and gelatin.
20. The core biopsy needle (1) according to claim 16, characterized in that said at least one tissue-adhesive compound is a chemical cross-linker, wherein particularly said chemical cross-linker is an aldehyde, more particularly formaldehyde or glutaraldehyde.
Description
[0099] Further embodiments and advantages may be derived from the figures and the example described hereafter, wherein the figures and the example are meant to illustrate the invention, but not to limit its scope.
[0100] FIG. 1 shows a schematic of a core biopsy needle according to the invention;
[0101] FIG. 2 shows a schematic of a core biopsy needle according to the invention in a first configuration inserted into a tissue of interest,
[0102] FIG. 3 shows a schematic of a core biopsy needle according to the invention in a second configuration inserted into a tissue of interest,
[0103] FIG. 4 shows a schematic of a core biopsy needle comprising a tissue sample;
[0104] FIG. 5 shows schematics of a tissue-holding surface of a core biopsy needle according to the invention, comprising pyramid shaped protrusions;
[0105] FIG. 6 shows schematics of a tissue-holding surface of a core biopsy needle according to the invention, comprising saw tooth shaped protrusions in a first arrangement;
[0106] FIG. 7 shows schematics of a tissue-holding surface of a core biopsy needle according to the invention, comprising saw tooth shaped protrusions in a second arrangement;
[0107] FIG. 8 shows schematics of a tissue-holding surface of a core biopsy needle according to the invention, comprising shark fin shaped protrusions;
[0108] FIG. 9 shows schematics of a tissue-holding surface of a core biopsy needle according to the invention, comprising brush shaped protrusions;
[0109] FIG. 10 shows micro biopsy needle grading based on the quality of the extracted tissue for histopathology.
[0110] FIG. 1 shows a core biopsy needle 1 extending along a longitudinal axis L, wherein the core biopsy needle 1 comprises a hollow outer needle 10 having a maximum cross-sectional extension e.sub.max transversely to the longitudinal axis L, and an inner needle 20, which is partially arranged within the outer needle 10. At the proximal end of the core biopsy needle 1 (left end in FIG. 1), the outer needle 10 comprises a cutting edge 11, and the inner needle 20 comprises a facet cut 23 ending in a stitching edge 22. The inner needle 20 further comprises a notch 24 and a tissue-holding surface 21 positioned at the bottom of the notch 24. The tissue-holding surface 21 is adapted to adhere by chemisorption, physisorption, and/or friction to a tissue 3 provided at the tissue-holding surface 21, for example by means of protrusions 40 on the tissue-holding surface 21 (thereby enhancing the friction between the tissue-holding surface 21 and the tissue 3), or by means of a tissue-adhesive compound comprised in the tissue-holding surface 21. For example, the tissue-holding surface 21 may consist of the tissue-adhesive compound or may be coated with the tissue-adhesive compound.
[0111] FIG. 2 illustrates the functional principle of the core biopsy needle 1 in conjunction with FIGS. 3 and 4. Therein, FIG. 2 depicts the core biopsy needle 1 in a first configuration in which a section of the inner needle 20 is inserted into a tissue region 30, of a tissue 3, particularly a tumor. Compared to the configuration shown in FIG. 1, the inner needle 20 is extended forward into the tissue 3 in respect of the outer needle 10. For example, this relative movement between the inner needle 20 and the outer needle 10 may be achieved by a spring load mechanism, or comparable means known from the prior art. The inner needle 20 is adapted to penetrate the tissue 3 when moving forward, particularly due to its stitching edge 22. The notch 24 of the inner needle 20 is positioned within the tissue region 30, such that a part of the tissue 3 from the tissue region 30 is forced into the notch 24. Thus, a part of the surface of this part of tissue 3 adheres to the tissue-holding surface 21, such that the friction between the tissue 3 and the tissue-holding surface 21 is enhanced, or such that the tissue 3 binds to the tissue-holding surface 21, for example by adhesion.
[0112] FIG. 3 illustrates a second configuration of the core biopsy needle 1, wherein the core biopsy needle 1 is partially positioned in the tissue 3, and wherein the outer needle 10 has been moved forward along the longitudinal axis L into the tissue region 30, for example by means of a further spring load mechanism. During the forward movement of the outer needle 10 in respect of the inner needle 20, the cutting edge 11 of the outer needle 10 generates a cut 32 in the tissue 3 in the tissue region 30, which separates the tissue 3 in the notch 24 from the surrounding tissue 3, thus forming a tissue sample 31 enclosed by the outer needle 10. During the cutting procedure and thereafter, the tissue sample 31 is fixed and mechanically stabilized by its adhesion to the tissue-holding surface 21, such that the tissue sample 31 stays complete during the biopsy.
[0113] FIG. 4 shows the core biopsy needle 1 after it has been removed from the tissue 3. The tissue sample 31 is contained in the notch 24 fixed and stabilized by the tissue-holding surface 21 and enclosed by the outer needle 10. In a further step, the complete tissue sample 31 can be removed from the notch 24 in order to analyze the tissue sample 31, for example by histology techniques according to the prior art in order to identify whether the tissue sample 31 contains tumor cells.
[0114] FIGS. 5 to 9 show schematics of different embodiments of the tissue-holding surface 21 of the inner needle 20 of a core biopsy needle 1 according to the invention, wherein the tissue-holding surface 21 comprises protrusions 40 to enhance friction between the tissue 3 and the tissue-holding surface 21.
[0115] The schematics and diagrams depicted in FIGS. 5 to 9 are not drawn to scale, but are meant to illustrate general examples of the arrangement and shape of the protrusions 40 of the tissue-holding surface 21. In particular, the size of the protrusions 40 depicted in FIGS. 5C, 6C, 7C, 8C and 9C does not correspond to the scale of the respective schematically drawn second needle 20. As described above, favorable embodiments of the tissue-holding surface 21 comprise protrusions 40 in the micrometer range, whereas the outer diameter of the inner needle 20 is typically in the sub-millimeter to millimeter range. However, the schematic representation of the inner needle 20 is included in the drawings to illustrate the orientation of the width x and length y of the protrusions 40.
[0116] The width x extends along a circumferential direction in respect of the longitudinal axis L, the length y extends along said longitudinal axis L, and the height z extends along a radial direction in respect of the longitudinal axis L. Due to the curvature of the inner needle 20, as thus the curvature of the tissue-holding surface 21, the schematics depicted in FIGS. 5 to 9 are idealized projections illustrating the approximate positioning of the protrusions 40.
[0117] FIG. 5 shows a first embodiment of the tissue-holding surface 21 comprising protrusions 40 having the shape of pyramids 43 with a square-shaped base 44.
[0118] FIG. 5A shows a cross-section of a protrusion 40 along the plane formed by the width x and the height z, and FIG. 5B shows a cross-section of a protrusion 40 along the plane formed by the length y and the height z. The edges 46 delimiting the cross-sectional shape of the protrusions 40 and an angle between two edges 46 are also depicted in FIGS. 5A and 5B.
[0119] FIG. 5C shows a top view of the arrangement of protrusions 40 on the tissue-holding surface 21 (the area enclosed by the dashed box). The edges of the pyramid-shaped protrusions 40 are depicted as dashed lines, wherein the respective peaks 41 of the pyramids 43 are positioned at the respective intersection of the edges (dashed lines). The position of the peaks 41 is also displayed in FIGS. 5A and 5B.
[0120] FIG. 6 shows a further embodiment of the tissue-holding surface 21 comprising protrusions 40 having a saw tooth shape.
[0121] FIG. 6A shows the triangular cross-section of a saw tooth shaped protrusion 40 along the plane formed by the width x and the height z, and FIG. 6B shows a rectangular cross-section of the protrusion 40 along the plane formed by the length y and the height z. Two edges 46 of the triangular cross-sectional shape arranged at an angle are also depicted in FIG. 6A. Therein, the angle may be an acute, obtuse, or right angle. In particular, the angle is between 0 and 90. The two edges 46 adjacent to the angle are particularly of equal length, in other words the respective triangular shape is an isosceles triangle.
[0122] FIG. 6C shows a top view of an arrangement of saw tooth shaped protrusions 40 on the tissue-holding surface 21 (enclosed by dashed box). The shapes of the respective bases 44 of the protrusions 40 are depicted as solid lines, and ridges 45 (lines of maximum height z) are displayed as dashed lines. The position of the ridge 45 in the respective cross-section is also depicted in FIGS. 6A and 6B.
[0123] In the embodiment shown in FIG. 6C, the protrusions 40 comprise rectangular bases, wherein the longer edges of the respective rectangles and the central ridges 45 extend along the length y.
[0124] FIG. 7 shows a further embodiment of the tissue-holding surface 21 comprising protrusions 40 having a saw tooth shape.
[0125] FIG. 7A shows the rectangular cross-section of a saw tooth shaped protrusion 40 along the plane formed by the width x and the height z, and FIG. 7B shows a triangular cross-section of the protrusion 40 along the plane formed by the length y and the height z. Two edges 46 of the triangular cross-sectional shape arranged at an angle are also depicted in FIG. 7B. Therein, the angle may be an acute, obtuse, or right angle. In particular, the angle is between 0 and 90. The two edges 46 adjacent to the angle are particularly of equal length, in other words the respective triangular shape is an isosceles triangle.
[0126] FIG. 7C shows a top view of an arrangement of saw tooth shaped protrusions 40 on the tissue-holding surface 21 (enclosed by dashed box). The shapes of the respective bases 44 of the protrusions 40 are depicted as solid lines, and ridges 45 (lines of maximum height z) are displayed as dashed lines. The position of the ridge 45 in the respective cross-section is also depicted in FIGS. 7A and 7B.
[0127] In the embodiment shown in FIG. 7C, the protrusions 40 comprise rectangular bases, wherein the longer edges of the respective rectangles and the central ridges 45 extend along the width x.
[0128] FIG. 8 shows a further embodiment of the tissue-holding surface 21 comprising protrusions 40 having a shark fin shape.
[0129] FIG. 8A shows the rectangular cross-section of a shark fin shaped protrusion 40 along the plane formed by the width x and the height z, and FIG. 7B shows the cross-section of the shark fin shaped protrusion 40 along the plane formed by the length y and the height z, wherein a curvature 42 of the surface between a ridge 45 (line of maximum height z) and the lowest point of the protrusion 40 is displayed in FIG. 8B.
[0130] FIG. 8C shows a top view of an arrangement of shark fin shaped protrusions 40 on the tissue-holding surface 21 (enclosed by dashed box). The shapes of the respective rectangular bases 44 of the protrusions 40 are depicted as solid lines. The ridges 45 coincide with the respective left long edge of the respective rectangular base 44. The position of the ridge 45 is also depicted in FIGS. 8A and 8B.
[0131] FIG. 9 shows a further embodiment of the tissue-holding surface 21 comprising protrusions 40 having a brush like shape.
[0132] FIG. 9A shows the triangular cross-section of a brush like protrusion 40 along the plane formed by the width x and the height z, and FIG. 9B shows the triangular cross-section of the brush like protrusion 40 along the plane formed by the length y and the height z. Two edges 46 of the triangular cross-sectional shape arranged at an angle are also depicted in FIGS. 9A and 9B. Therein, the angle may be an acute, obtuse, or right angle. In particular, the angle is between 0 and 90 . The two edges 46 adjacent to the angle are particularly of equal length, in other words the respective triangular shape is an isosceles triangle.
[0133] FIG. 9C shows a top view of an arrangement of brush like protrusions 40 on the tissue-holding surface 21 (enclosed by dashed box). The shapes of the respective circular bases 44 of the protrusions 40 are depicted as solid lines, and the peaks 41 (points of maximal height z) are indicated as dots. The position of the peaks 41 is also depicted in FIGS. 9A and 9B.
[0134] Further embodiments and advantages of the present invention may be derived from the following example.
Example
[0135] Based on the analysis of native tissue surface waviness and roughness approximately 20 different micro-patterns with varying size (e.g. but not limited to: xy dimension 20-100 m and z dimension 10-80 m) and shape (e.g. but not limited to: pyramids, brushes, saw tooth, shark fin) were designed. These microstructures were laser ablated into stainless steel plates, which were used as templates for polymer molding (for example into PDMS) of the structures.
[0136] Dynamic and static friction behavior between stainless steel templates or PDMS molds and cow udder tissue specimens were measured to identify the most adhesive microstructures (structure selection shown in Table 1, most potent structures in bold .sub.stat,Unstr refers to the static friction coefficient of the unstructured surface, and .sub.dyn,Str dyn Str refers to the dynamic friction coefficient of the structured surface.
[0137] As an example but not limited to, polymer molds that include PDMS and a cyanoacrylate bases glue were tested. Adhesion experiments have also been performed on chemically modified polymer microstructures. As an example but not limited to; PDMS surfaces have been functionalized with Arginine-Glycine-Aspartic acid (RGD), Poly-L-lysine (PLL), Collagen I and/or a cyanoacrylate based glue.
[0138] Successful extraction of cow udder core biopsy by micro structuring (selected from Table 1) commercially available 20 gauge core biopsy needles was achieved. The patterning was performed either by direct laser ablation into or by micro structuring polymer coatings onto the inner needle notch.
[0139] Extracted tissue specimens were examined by standard histopathology (Haematoxilin & Eosin staining) to determine tissue integrity and cell preservation (FIG. 10). The main criterion was to obtain a compact and non-fragmented biopsy that is acceptable for histopathology. In contrast to micro structured needles according to the present invention, biopsies from non-modified standard 20 gauge core biopsy needles were fragmented and could not be used for histopathology.
TABLE-US-00001 TABLE 1 List of tested micro patterned adhesive surfaces Structure [00001] Static Rank [00002] Dynamic Rank Spring Constant [Nmm.sup.1] Pyramids 5.2 2 7.8 1 0.155 Pyramids 2.7 6 2.8 7 0.021 inv. Saw 10.9 1 5.3 4 0.112 tooth 1 Saw 3.3 4 4.7 5 0.073 tooth 2 Shark 3.1 5 5.8 2 0.055 Fin 1 Shark 5.1 3 5.6 3 0.072 Fin 2 Brush 1 1.9 8 4.2 6 0.065 Brush 2 2.5 7 7.8 1 0.153
LIST OF REFERENCE SIGNS
[0140]
TABLE-US-00002 1 Core biopsy needle 10 Outer needle 11 Cutting edge 20 Inner needle 21 Tissue-holding surface 22 Stitching edge 23 Facet cut 24 Notch 3 Tissue 30 Tissue region, particularly tumour 31 Tissue sample 32 Cut 40 Protrusion 41 Peak 42 Curvature 43 Pyramid 44 Base 45 Ridge 46 Edge L Longitudinal axis e.sub.max Maximum extension x Width y Length z Height angle
