Tissue sampling instrument

Abstract

A tissue sampling device may include a handle comprising a deployment mechanism, a cannula, and a stylet. The cannula is insertable into an endoscopic lumen of an endoscope. The cannula defines a first lumen extending from the proximal end to the distal end of the cannula. The stylet is disposed within the first lumen. The stylet includes a proximal end coupled to a second portion of the deployment mechanism and a distal end spaced apart from the handle along the longitudinal axis. The stylet comprises a cutting edge on the distal end and defines a specimen notch spaced from the cutting edge. Each of the stylet and the cannula are independently movable in a longitudinal direction with respect to each other and are deployable in the longitudinal direction by the deployment mechanism. Each of the stylet and the cannula is flexible along its length.

Description

TISSUE SAMPLING INSTRUMENTCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 602,780, filed November 27, 2023, and U.S. Provisional Patent Application No. 63 / 650,053, filed May 21, 2024, the entire contents of which are incorporated herein by reference.BACKGROUND

[0002] The present disclosure relates generally to tissue sampling (e.g., biopsy devices and processes). The TNM (tumor, node, metastasis) cancer staging system, derived from tumor corebiopsy (T stage) and cross-sectional imaging (N and M stages), helps to inform optimal cancer treatment and prognosis. However, existing biopsy instruments for sampling tumors / masses arising from the hollow viscera or luminal organs (e.g. tumors of the ureter, gastrointestinal tract including small bowel, colon and rectum, and pancreas, lungs and bronchi, trachea, genital tract, etc.) utilize surface biopsy techniques which lead to unreliable T staging. Therefore, a need exists for a more precise and efficient device and method for tissue sampling and biopsies.SUMMARY

[0003] Described herein are systems, methods, and devices (e.g., a biopsy instrument) that help patients with malignancies of luminal organs by improving clinical staging and molecular riskstratification, and guiding precision treatment. The systems, methods, and devices described herein are capable of obtaining a “full-thickness” biopsy of a target organ through a flexible, core biopsy mechanism (e.g., a tru-cut core biopsy). Referring generally to the figures, a tissue sampling device and system are shown, according to various implementations. In one example, a biopsy instrument for optimal sampling of upper tract urothelial carcinoma (UTUC) is disclosed.

[0004] The TNM (tumor, node, metastasis) staging, derived from tumor core-biopsy (T stage) and cross-sectional imaging (N and M stages), is pivotal in guiding optimal cancer treatment and prognosis. However, for patients with upper tract urothelial carcinoma (UTUC), a standardized core biopsy technique is lacking. Upper tract urothelial carcinoma (UTUC) afflicts approximately 4,000 new patients in the United States each year. Additionally, approximately 30,000 survivors are living with it, who are being managed via organ-sparing treatments.

[0005] For example, FIG. 1 shows an anatomical diagram of a bladder, kidneys, and ureters therebetween. FIG. 1 shows a ureteral tumor in the ureter and a renal pelvic tumor in the kidney.In the diagram of FIG. 1 showing a cross-sectional view of the ureteral tumor, the various tumor stages are visible. For example, stages CIS and Ta tumors are shown on the surface of the urothelium. Stage T1 and T2 tumors are shown to extend deeper into the submucosa and muscle, respectively. Finally, stage T3 and T4 tumors are shown extending beyond the muscle layer into the surrounding adipose tissue and into other organs. Notably, the depth of the tumor may vary greatly while the surface-level size of the tumor remains substantially the same. Thus, a surfacelevel biopsy may not adequately detect a difference between T1 and T4 stages, for example.

[0006] The existing biopsy systems for UTUC only allow for surface biopsies of the tumor, which do not reveal the tumor depth (T stage). Some existing systems rely on baskets or grasping forceps to retain a portion of the tumor, which can be unreliable and still only retain a surface portion of the tumor. Additionally, using such instruments leads to loss of histological architecture, precluding accurate prognostication / staging of the tumor. Consequently, nearly 50% of patients are inaccurately staged, leading them to receive inappropriate treatment. Suboptimal treatments are associated with the loss of organs or life. This issue is amplified when examining the broader scope of luminal malignancies in general, impacting organ systems such as the GI tract, pancreas, and respiratory system. Existing devices and systems for biopsy, specifically relating to UTUC and hollow Gl / pulmonary viscus, provide only surface-biopsy instruments (e.g., wire baskets, forceps) for diagnosing luminal cancers. As a result, the existing devices and systems do not offer accurate T staging information.

[0007] In contrast, the systems, methods, and devices described herein are capable of obtaining a “full-thickness” biopsy of a target organ through a flexible, tru-cut core biopsy mechanism. Thus, the systems, methods, and devices of this disclosure provide a technical advantage over the existing systems.

[0008] According to one implementation, a tissue sampling device is disclosed. The tissue sampling device includes a handle, a cannula, and a stylet. The handle includes a deployment mechanism. The cannula is insertable into an endoscopic lumen of an endoscope. The cannula has a proximal end coupled to a first portion of the deployment mechanism and a distal end spaced apart from the handle along a longitudinal axis. The cannula defines a first lumen extending from the proximal end to the distal end of the cannula. The stylet is disposed within the first lumen. The stylet has a proximal end coupled to a second portion of the deployment mechanism and a distal end spaced apart from the handle along the longitudinal axis. The stylet includes a cutting edge on the distal end and defines a specimen notch spaced from the cutting edge on the distal end of thestylet. Each of the stylet and the cannula are independently movable in a longitudinal direction with respect to each other and are deployable in the longitudinal direction by the deployment mechanism. Each of the stylet and the cannula is flexible along its length.

[0009] In some implementations, the tissue sampling device further includes a protective sheath having a proximal end coupled to a third portion of the handle and a distal end spaced apart from the handle along the longitudinal axis. The protective sheath defines a second lumen extending from the proximal end to the distal end of the protective sheath. The stylet and the cannula are both disposed within the second lumen and independently movable in the longitudinal direction with respect to the protective sheath.

[0010] In some implementations, the protective sheath is flexible along its length, and the distal end of the protective sheath includes a flexible portion being more flexible than the remainder of the protective sheath.

[0011] In some implementations, the deployment mechanism includes a sheath retractor on a distal end of the handle, the sheath retractor being rotatable and movable in the longitudinal direction with respect to the handle. The sheath retractor includes a locking member coupled to and extending transverse from the protective sheath. The sheath retractor defines one or more locking slots configured to engage the locking member and retain the protective sheath in one of a deployed position or a retracted position.

[0012] In some implementations, a first portion of the deployment mechanism is configured to move the stylet longitudinally with respect to each of the cannula, and a second portion of the deployment mechanism is configured to move the cannula longitudinally with respect to each of the stylet.

[0013] In some implementations, the first portion of the deployment mechanism includes a first button coupled to a first gear and the second portion of the deployment mechanism includes a second button coupled to a second gear.

[0014] In some implementations, the deployment mechanism is a spring-loaded deployment mechanism including a priming lever and a trigger. The first portion of the deployment mechanism is a first hub coupled to the proximal end of the stylet and the second portion of the deployment mechanism is a second hub coupled to the proximal end of the cannula. Each of the first hub andthe second hub is biased in an axially forward direction towards the distal end of the stylet and the cannula.

[0015] In some implementations, the tissue sampling device further includes a first snap-fit engageable with the first hub to retain the first hub in a primed position and a second snap-fit engageable with the second hub to retain the second hub in a primed position.

[0016] In some implementations, the trigger is movable to engage the first snap-fit and release the first hub from the primed position to a deployed position in the longitudinal direction.

[0017] In some implementations, the first hub abuts a follower that is movable to engage the second snap-fit and release the second hub from the primed position to a deployed position.

[0018] In some implementations, the priming lever is coupled to a priming member disposed along the handle adjacent to the first hub and the second hub. The priming lever and the priming member are moveable to push one or both of the first hub and the second hub longitudinally toward the primed position.

[0019] In some implementations, the deployment mechanism deploys the stylet at a speed in the range of 0.5 - 20 m / s. In some implementations, the speed is greater than 8 m / s.

[0020] In some implementations, the cutting edge of the stylet is a beveled edge. In some implementations, the distal end of the cannula includes a second cutting edge.

[0021] In some implementations, the distal end of the stylet is movable in the longitudinal direction to a first distance from the distal end of the cannula, and the distal end of the cannula is movable to a second distance. In some implementations, the first distance is equal to the second distance. In some implementations, the first distance is in the range of 2-20 mm.

[0022] In some implementations, the endoscope further includes a camera on a distal end of the endoscope.

[0023] In some implementations, the distal end of the cannula and the distal end of the stylet are both capable of curling in a variety of desired angles and orientations to facilitate navigation .

[0024] In some implementations, either one of the cannula, the stylet, or the protective sheath has a length from the proximal end to the distal end thereof in the range of 60cm-250cm.

[0025] In some implementations, the length is greater than 115cm.

[0026] In some implementations, either one of the cannula, the stylet, or the protective sheath has a diameter in the range of 2 - 12 Fr (0.67 - 4 mm). In some implementations, the diameter is less than 3.5 Fr.

[0027] According to another implementation, a method of collecting a tissue sample is disclosed. The method includes providing a tissue sampling device. The tissue sampling device includes a handle with a deployment mechanism, a cannula, and a stylet. The cannula has a proximal end coupled to a first portion of the deployment mechanism and a distal end spaced apart from the handle along a longitudinal axis. The cannula defines a first lumen extending from the proximal end to the distal end of the cannula. The stylet is disposed within the first lumen, the stylet having a proximal end coupled to a second portion of the deployment mechanism and a distal end spaced apart from the handle along the longitudinal axis. The stylet includes a cutting edge on the distal end and defines a specimen notch spaced from the cutting edge on the distal end of the stylet. The method further includes inserting the cannula of the tissue sampling device into an endoscopic lumen of an endoscope that extends into a living subject. The method further includes advancing the cannula until the distal ends of each of the cannula and the stylet are adjacent to a target tissue. The method further includes activating the first portion of the deployment mechanism to longitudinally extend the distal end of the stylet into the target tissue beyond the distal end of the cannula to expose the specimen notch. The method further includes activating the second portion of the deployment mechanism to longitudinally extend the distal end of the cannula into the target tissue to contain the specimen notch. The method further includes retracting the stylet and the cannula out of the living subject.

[0028] In some implementations, the step of activating the first portion of the deployment mechanism to longitudinally extend the distal end of the stylet includes cutting a portion of the target tissue with the cutting edge such that a specimen of the target tissue is disposed within the specimen notch.

[0029] In some implementations, the step of activating the second portion of the deployment mechanism to longitudinally extend the distal end of the cannula includes cutting a portion of the target tissue such that the specimen is removed from the target tissue to be fully retained by the specimen notch and the cannula.

[0030] In some implementations, the target tissue is a tumor or a mass in a hollow viscera or luminal organ.

[0031] In some implementations, the target tissue is a malignancy of a luminal organ.

[0032] In some implementations, the method further includes analyzing the target tissue and grading a cancer type of the target tissue.

[0033] In some implementations, the tissue sampling device further includes a protective sheath having a proximal end coupled to a third portion of the handle and a distal end spaced apart from the handle along the longitudinal axis. The protective sheath defines a second lumen extending from the proximal end to the distal end of the protective sheath. The stylet and the cannula are both disposed within the second lumen and independently movable in a longitudinal direction with respect to the protective sheath.

[0034] This summary is illustrative only and is not intended to be in any way limiting. Other aspects, features, and advantages of the devices or processes described herein will become apparent in the detailed description set forth herein, taken in conjunction with the accompanying figures, wherein like reference numerals refer to like elements.BRIEF DESCRIPTION OF DRAWINGS

[0035] The systems, methods, and devices are explained in even greater detail in the following drawings. The drawings are merely exemplary and certain features may be used singularly or in combination with other features. The drawings are not necessarily drawn to scale.

[0036] FIG. 1 shows an anatomical diagram of the bladder, kidneys, and ureters along with a cross-sectional diagram of different stages of tumor growth, according to one implementation.

[0037] FIG. 2 shows a diagram (not to scale) of a user holding a tissue sampling device coupled to an endoscope, according to one implementation.

[0038] FIG. 3 shows a diagram of a tissue sampling device disposed within a ureter, wherein the inset diagrams show the deployment of the stylet and cannula, according to one implementation.

[0039] FIG. 4 shows a diagram of the handle of the tissue sampling device being inserted into a port on the endoscope handle, wherein the inset diagram shows stages of the stylet and cannula deployment, according to one implementation.

[0040] FIG. 5 shows a diagram of the handle and deployment mechanism of the tissue sampling device, according to one implementation.

[0041] FIG. 6 shows a tissue sampling device, according to another implementation.

[0042] FIG. 7 shows a close view of the handle of the tissue sampling device of FIG. 6.

[0043] FIG. 8 shows a first side view of the handle of the tissue sampling device of FIG. 6.

[0044] FIG. 9 shows a second side view of the handle of the tissue sampling device of FIG. 6.

[0045] FIG. 10 shows an isometric view of the handle of the tissue sampling device of FIG. 6 with one side of the housing removed to reveal the inner components, according to one implementation.

[0046] FIG. 11 shows a side view of the handle of FIG. 10 with one side of the housing removed.

[0047] FIG. 12 shows a cross-sectional view of the distal end of the tissue sampling device of FIG. 6, including the stylet, cannula, and protective sheath, according to one implementation.

[0048] FIG. 13 shows a cross-sectional view of the distal end of the tissue sampling device of FIG. 6 along a plane perpendicular to the cross-sectional view of FIG. 12.

[0049] FIG. 14 shows a side view of the distal end of the tissue sampling device of FIG. 6 without the protective sheath, according to one implementation.

[0050] FIG. 15 shows a side view of the stylet of the tissue sampling device of FIG. 6, according to one implementation.

[0051] FIG. 16 shows a partial isometric view of the stylet of the tissue sampling device of FIG. 6, according to one implementation.DETAILED DESCRIPTION

[0052] Following below are more detailed descriptions of concepts related to, and implementations of, methods, apparatuses, and systems for a tissue sampling instrument. The figures illustrate exemplary implementations in detail and the present disclosure is not limited tothe details or methodology set forth in the description or illustrated in the figures. The terminology used herein is for the purpose of description only and should not be regarded as limiting.

[0053] The systems, methods, and devices described herein are capable of obtaining a “fullthickness” biopsy of a target organ through a flexible, tru-cut core biopsy mechanism. In one example, a biopsy instrument for optimal sampling of upper tract urothelial carcinoma (UTUC) is disclosed.

[0054] The TNM (tumor, node, metastasis) staging, derived from tumor core-biopsy (T stage) and cross-sectional imaging (N and M stages), is pivotal in guiding optimal cancer treatment and prognosis. However, for patients with upper tract urothelial carcinoma (UTUC), a standardized core biopsy technique is lacking.

[0055] For example, FIG. 1 shows an anatomical diagram of a bladder, kidneys, and ureters therebetween. FIG. 1 shows a ureteral tumor (e.g., UTUC) with a cross-sectional view of the showing the various tumor stages. For example, stages CIS and Ta tumors are shown on the surface of the urothelium. Stage T1 and T2 tumors are shown to extend deeper into the submucosa and muscle, respectively. Finally, stage T3 and T4 tumors are shown extending beyond the muscle layer into the surrounding adipose tissue and into other organs. Notably, the depth of the tumor may vary greatly while the surface-level size of the tumor remains substantially the same. Thus, a surface-level biopsy may not adequately detect a difference between T1 and T4 stages, for example.

[0056] The existing biopsy systems for UTUC only allow for surface biopsies of the tumor, which do not reveal the tumor depth (T stage). Some existing systems rely on baskets or grasping forceps to retain a portion of the tumor, which can be unreliable and still only retain a surface portion of the tumor. Additionally, using such instruments leads to loss of histological architecture, precluding accurate prognostication / staging of the tumor. Consequently, nearly 50% of patients are inaccurately staged, leading them to receive inappropriate treatment. Suboptimal treatments are associated with the loss of organs or life. This issue is amplified when examining the broader scope of luminal malignancies in general, impacting organ systems such as the GI tract, pancreas, and respiratory system. Existing devices and systems for biopsy, specifically relating to UTUC and hollow Gl / pulmonary viscus, provide only surface-biopsy instruments (e.g., wire baskets, forceps) for diagnosing luminal cancers. As a result, the existing devices and systems do not offeraccurate T staging information. Additionally, existing systems lack the flexibility to both navigate intraluminal anatomy and penetrate a target tissue to a desired depth.

[0057] In contrast, the systems, methods, and devices described herein are capable of obtaining a “full-thickness” biopsy of a target organ through a flexible, tru-cut core biopsy mechanism. This disclosure allows for core sampling of a desired tissue target within an intraluminal space (e.g., UTUC). The example device provides a fast deployment mechanism (e.g., spring-loaded or geared drive system) that moves the cutting body with enough speed and force to collect a core sample from the target tissue. Thus, the systems, methods, and devices of this disclosure provide a technical advantage over the existing systems.

[0058] Described herein is an example method and system for collecting a core-biopsy sample of an upper tract urothelial carcinoma (UTUC). However, this disclosure contemplates variations in structure and use beyond that of biopsy collection for UTUC. In some implementations, the devices contemplated may be used for tissue collection in a different anatomical location (e.g., the GI tract, respiratory system, or the vascular system). In some implementations, the devices contemplated may be used in any tubular or intraluminal space. In general, a luminal space may be defined as the cavity or channel within a tube or tubular organ. In some implementations, the tissue sample collected is used for a purpose other than a biopsy.Example System, Method, and Device #1

[0059] FIGS. 2-6 show a tissue sampling device 100, according to one implementation. The tissue sampling device 100 includes a handle 110, a cannula 120, and a stylet 130. The tissue sampling device 100 is insertable into an endoscope 10 that includes a handle 12 and an introducer sheath 14. Specifically, the cannula 120 and the stylet 130 of the device 100 are configured to be inserted into the introducer sheath 14 of the endoscope 10 as further described below.

[0060] FIG. 2 shows the endoscope 10 (not to scale) with the tissue sampling device 100 configured for a ureteroscopy procedure. FIG. 3 shows a diagram of the flexible cannula 120 and the stylet 130 on the distal end 104 of the device 100 disposed within the ureter. Specifically, the flexible cannula 120 and the stylet 130 enter through the urethra, through the bladder, and into the ureter below the kidney. The distal end 104 of the device 100 may be moved into position in the ureter adjacent to an upper tract urothelial carcinoma. The biopsy device 100 of this example isconfigured to extend into a tumor to cut and collect a core biopsy at a desired depth, as further described below.

[0061] The flexible shaft of the device 100 with the cannula 120 and the stylet 130 has a length significantly longer than existing biopsy devices. In some examples, the flexible shaft has a length greater than 115cm (e.g., 200cm) to effectively reach the relevant sites within a luminal organ of a patient’s body. In some implementations, the length of the flexible shaft is in a range of 60cm - 250cm (e.g., 80cm, 100cm, 120cm, 140cm, 160cm, 180cm, 200cm, 220cm, or 240cm).

[0062] Additionally, the diameter of the flexible shaft (e.g., the diameter of the cannula 120) is smaller than existing devices. In some examples, the flexible shaft has a diameter of less than 3.5 Fr (<1.17mm) to effectively reach tumors at the relevant sites. In some implementations, the flexible shaft has a diameter in the range of 2 - 12 Fr (e.g., 2 Fr, 2.5 Fr, 3 Fr, 3.5 Fr, 4 Fr, 5 Fr, 6 Fr, 7 Fr, 8 Fr, 9 Fr, 10 Fr, 11 Fr, or 12 Fr). The small size further facilitates the passage of the flexible shaft and other elements of the device through the small luminal organs (e.g., the ureter). The above-described sizes apply to the device 100 and other exemplary devices herein described.

[0063] FIG. 4 shows the tissue sampling device 100 wherein the cannula 120 and the stylet 130 are inserted into the introducer sheath 14 of the endoscope 10. The handle 110 of the device 100 extends from a port on a side of the handle 12 of the endoscope 10. FIG. 4 also shows a progression of the deployment of the cannula 120 and the stylet 130, according to one implementation.

[0064] The cannula 120 of the device 100 defines a lumen 122. The cannula 120 includes a proximal end coupled to a portion of the handle 110 and a distal end opposite and spaced apart from the proximal end along a longitudinal axis. The cannula 120 is a flexible outer shell or tube of the tissue sampling device 100 that provides an outer surface that contacts the tissue of the living subject. However, in other implementations, an additional containment sheath is disposed around the cannula to contact the tissue of the living subject.

[0065] The cannula 120 is flexible and bendable to controllably conform to the anatomy of the living subject (e.g., the pathway of the ureter of a living subject). In the implementation shown, at least a major part of the cannula 120 and the stylet 130 are flexible along their length as well. The distal end of the cannula 120 includes a cutting edge 124. For example, the cannula 120 may include a beveled cutting edge 124. The cutting edge 124 may extend circumferentially around the distal opening of the lumen 122.

[0066] The stylet 130 extends through the lumen 122 defined by the cannula 120. The stylet 130 includes a proximal end coupled to a portion of the handle 110 and a distal end opposite and spaced apart from the proximal end along a longitudinal axis. The distal end of the stylet 130 includes a cutting edge 132 (e.g., a beveled cutting edge or an annular-bladed tip) configured to extend into a target tissue of a living subject.

[0067] The stylet 130 includes a specimen notch 134 defined by the body of the stylet 130 and extending in a longitudinal direction. For example, the specimen notch 134 may be defined a distance away from the cutting edge 132. The specimen notch 134 may have a depth in the radial direction that is half of the diameter of the stylet 130. The stylet 130 is configured to extend into a target tissue to collect a specimen or sample within the specimen notch 134.

[0068] The stylet 130 is also flexible and bendable to controllably conform to the anatomy of the living subject, similar to the cannula 120. In other implementations, the stylet may include a portion smaller than the entire length of the introducer sheath of the endoscope or the cannula. For example, the specimen notch may be disposed on a portion of an end effector having a length contained to the tip of the device (e.g., several millimeters or centimeters at the distal end of the stylet). In other implementations, the stylet and the cannula have the same truncated length at the distal end of the device. In other implementations, the stylet is coupled to a flexible actuation wire extending back to the handle of the device. In other implementations, a portion of the stylet (e.g., a distal end including the specimen notch) is relatively rigid compared to the remainder of the cutting body and the cannula to facilitate entry into the anatomy / specimen site.

[0069] As shown in FIG. 4, each of the stylet 130 and the cannula 120 are independently movable in a longitudinal direction with respect to each other and with respect to the introducer sheath 14 of the endoscope 10. The movement of each of the stylet 130 and the cannula 120 is controlled by the operation of a deployment mechanism within the handle 110 to collect a tissue sample, as will be further described below. However, a variety of specific actuation mechanisms and deployment devices are contemplated by the present disclosure (e.g., buttons, triggers, handles, and knobs that may be spring-loaded, spring-actuated, motor-actuated, level-actuated, or otherwise configured to deploy one of the stylet or the cannula). In other implementations, the deployment mechanism is any mechanical or electromechanical system configured to extend the stylet longitudinally into the target tissue to a desired distance with enough speed and force to collect a core sample of the tissue.

[0070] In the retracted state (A) of FIG. 4, the distal ends of the stylet 130 and the cannula 120 are disposed within the introducer sheath 14 of the endoscope 10. The device 100 may initially be in the retracted state to begin a biopsy procedure and as the distal end of the device 100 is navigated through the anatomy to the target site. The device 100 may be controlled to bend and angle to orient itself in the desired direction. Optionally, a camera and light on the tip of the device 100, or the endoscope 10, can help guide the device 100 to the target tissue.

[0071] Once at the target site, the stylet 130 is actuated to extend axially from a distal opening of the introducer sheath 14, as shown in the first deployment state (B) in FIG. 4. For example, the deployment mechanism provides enough force / speed to deploy the stylet 130 and the specimen notch 134 thereon and penetrate the desired distance into the luminal organ tumor tissue, which may be resistant to penetration or relatively firm compared to other organ structures. For example, the walls of luminal organs are quite elastic and muscular and can vary vastly (e.g., ureter and gastrointestinal systems are quite similar to each other but quite different from tracheal tissue, which is more rigid due to higher cartilaginous content). Hence, for adequate penetration, the device 100 provides a quick penetrative ability to utilize the inertia of the organ against itself. The device 100 not only allows full-thickness penetration but also better preservation of tissue architecture. In some implementations, the deployment mechanism deploys the stylet at a speed of 3m / s or greater (e.g., 8m / s). In some implementations, the deployment mechanism deploys the stylet at a speed in the range of 0.5 - 20 m / s (e.g., 0.5 m / s, 1 m / s, 2 m / s, 4 m / s, 6 m / s, 8 m / s, 10 m / s, 12 m / s, 15 m / s, or 20 m / s).

[0072] Once deployed, the specimen notch 134 received a portion of the target tissue (e.g., the sample tissue). Then, to protect and retain the sample tissue, the cannula 120 is actuated to extend axially out of the introducer sheath 14, as shown in the second deployment state (C) in FIG. 4. For example, the cannula 120 extends over the specimen notch 134 and the sample tissue therein to seal and retain the sample tissue. The device 100 may then be retracted out of the patient and the sample collected from the specimen notch 134.

[0073] The handle 110 of the tissue sampling device 100 includes a deployment mechanism (e.g., a gear system, a spring-loaded system, an electronic system, a motorized system, a pneumatic system, or any other fast-acting actuation system). As shown, tissue sampling device 100 is insertable into a port on the side of the handle 12 of the endoscope 10. Once inserted, the handle

[0074] FIG. 5 shows the handle 110 of the device 100 along with the actuation mechanism. Specifically, the actuation mechanism of FIG. 5 is a two-stage actuation mechanism. A proximal portion of the handle 110 includes two buttons - a first button 140 and a second button 150. The first button 140 is mechanically coupled to and configured to actuate the stylet 130. The second button 150 is mechanically coupled to and configured to actuate the cannula 120.

[0075] The first button 140 includes a toothed arm 142 extending into the inner cavity of the handle 110. A stepped gear 144 is disposed adjacent to the first button 140. A small diameter gear of the stepped gear 144 engages with the toothed arm 142. A large diameter gear of the stepped gear 144 engages with a toothed actuation member 146 that is coupled to the proximal end of the stylet 130. In use, pressing down the first button 140 causes the toothed arm 142 to rotate the small gear of the stepped gear 144. Then, the large gear rotates correspondingly to engage the toothed actuation member 146. Then, the toothed actuation member 146 urges the stylet 130 longitudinally with respect to the cannula 120. This action is shown in panel (A) of FIG. 5, wherein the specimen notch 134 is partially exposed as the stylet 130 is deployed.

[0076] The second button 150 includes a toothed arm 152 extending into the inner cavity of the handle 110. A stepped gear 154 is disposed adjacent to the second button 150. A small diameter gear of the stepped gear 154 engages with the toothed arm 152. A large diameter gear of the stepped gear 154 engages with a toothed actuation member 156 that is coupled to the proximal end of the cannula 120. In use, pressing down the second button 150 causes the toothed arm 152 to rotate the small gear of the stepped gear 154. Then, the large gear rotates correspondingly to engage the toothed actuation member 156. Then, the toothed actuation member 156 urges the cannula 120 longitudinally with respect to the stylet 130. This action is shown in panel (B) of FIG. 5, wherein the specimen notch 134 is enclosed as the cannula 120 is deployed.

[0077] In operation, a method of collecting a tissue sample (e.g., a sample of a tumor for biopsy) is disclosed using the example device 100. The distal end of the device 100 - including the distal ends of the stylet 130 and the cannula 120 - is advanced into a living subject and towards a target tissue (e.g., into the urethra and towards a UTUC; or into another intraluminal anatomy). The device 100 may be controlled to bend and angle to orient itself in the desired direction. Optionally, a camera and light on the tip of the device 100, or on a separately inserted endoscope, can help guide the device 100 to the target tissue.

[0078] The device and associated method disclosed herein are configured for quick deployment of the cutting body into the target tissue to collect a core sample of the tissue. Recall that for many cancer types, including upper tract urothelial carcinoma (UTUC), a standardized core biopsy technique is lacking. The existing biopsy systems for UTUC only allow for surface biopsies of the tumor, which do not reveal the depth. Without depth data, these systems fail to adequately evaluate the T stage of the TNM (tumor, node, metastasis) cancer staging, leading to issues in treatment plans and prognosis. Additionally, existing systems lack the flexibility to both navigate intraluminal anatomy and penetrate a target tissue to a desired depth. By contrast, this novel system allows for core sampling of a desired tissue target within an intraluminal space (e.g., UTUC). The example device 100 provides a fast deployment mechanism (e.g., spring-loaded or geared drive system) that moves the cutting body with enough speed and force to collect a core sample from the target tissue.Example System, Method, and Device #2

[0079] As another example implementation of the systems, methods, and devices disclosed herein, FIGS. 6-16 show a tissue sampling device 200. The tissue sampling device 200 extends from a proximal end 202 to a distal end 204 opposite and spaced apart from the proximal end 202 along a longitudinal axis 201. The tissue sampling device 200 includes a handle 210, a cannula 220, a stylet 230, and a protective sheath 240. The tissue sampling device 200 is configured to be inserted into a lumen of an endoscope and into a living subject, similar to the device 100 of FIGS. 2-5. The tissue sampling device 200 is configured to capture a core biopsy sample of a tumor of a luminal organ (e.g., UTUC), similar to the device 100 of FIGS. 2-5. All of the sizes, diameters, lengths, forces, speeds, and other numerical values associated with the device 100 are applicable to the device 200 of FIGS. 6-16.

[0080] FIGS. 7-11 show various views of the handle 210. The handle 210 includes a proximal end 212 and a distal end 214 opposite and spaced apart from the proximal end 212 along the longitudinal axis 201. The handle 210 includes a housing 250 defining an inner cavity 252, as shown in FIGS. 10-11. The housing 250 shown is a two-part shell housing wherein both halves of the housing 250 are couplable together (e.g., via screws or other fasteners). Furthermore, an end plate 254 is disposed on the distal end 214 of the handle 210 to enclose the distal end 214 of the inner cavity 252. FIGS. 10-11 are shown without one-half of the housing 250 so that the inner components are visible.

[0081] The deployment mechanism of the handle 210 of the tissue sampling device 200 is a spring-loaded deployment mechanism that is movable between a primed position and a deployed position. Specifically, the handle 210 includes a first hub 260 coupled to a proximal end of the stylet 230 and a second hub 270 coupled to a proximal end of the cannula 220 (e.g., friction fit, fixed via adhesive, molded together, or integrally formed). The first hub 260 is disposed further towards the proximal end 212 of the inner cavity 252 of the handle 210 relative to the second hub 270. Each of the first hub 260 and the second hub 270 are moveable in a longitudinal direction between the primed position and the deployed position.

[0082] The first hub 260 is spring loaded via a biasing member 262 abutting a proximal end of the first hub 260. The biasing member 262 biases the first hub 260 in a deployment direction or a firing direction (e.g., an axially forward direction) towards the distal end 214 of the handle 210. A first side of the first hub 260 includes a priming protrusion 264, and an opposite second side of the first hub 260 includes a locking protrusion 266.

[0083] A first pivoting snap-fit 268 is disposed adjacent to the second side of the first hub 260. The first pivoting snap-fit 268 is movable to engage with the locking protrusion 266 of the first hub 260 to retain the first hub 260 in the primed position. The first pivoting snap-fit 268 is also moveable (e.g., rotatable) to allow movement of the first hub 260 towards the distal end 214 of the handle 210, as further described below.

[0084] The second hub 270 is spring loaded via a biasing member 272 abutting a proximal end of the second hub 270. The biasing member 272 biases the second hub 270 in the deployment direction or the firing direction towards the distal end 214 of the handle 210. A first side of the second hub 270 includes a priming protrusion 274, and an opposite side of the second hub 270 includes a locking protrusion 276.

[0085] A second pivoting snap-fit 278 is disposed adjacent to the second side of the second hub 270. The second pivoting snap-fit 278 is movable to engage with the locking protrusion 276 of the second hub 270 to retain the second hub 270 in the primed position. The second pivoting snap-fit 278 is also moveable (e.g., rotatable) to allow movement of second hub 270 towards the distal end 214 of the handle 210, as further described below.

[0086] A follower 256 is disposed in between the first hub 260 and the second hub 270. The follower 256 includes a proximal surface configured to abut a portion of the first hub 260. Thefollower 256 includes a distal surface configured to abut a portion of the second pivoting snap-fit 278. The follower 256 is biased (e.g., via a spring) towards the proximal end 212 of the handle 210.

[0087] The handle 210 further includes a priming lever 216 coupled to a first side of the handle 210. The handle 210 also includes a trigger 218 coupled to a second side of the handle 210 opposite from the priming lever 216 (e.g., diametrically opposed). The priming lever 216 extends through the housing 250 on the first side of the handle 210, and the trigger 218 extends through the housing 250 on the second side of the handle 210.

[0088] The priming lever 216 on the first side of the handle 210 is coupled to a priming bar 280 that extends longitudinally along the inner cavity 252. The priming bar 280 defines openings engageable with each of the first hub 260 and the second hub 270. Specifically, the priming bar 280 defines an opening engageable with the priming protrusion 264 of the first hub 260 and another opening engageable with the priming protrusion 274 of the second hub 270.

[0089] The priming lever 216 is pivotable about a pivot point 282 on a proximal end of the priming lever 216. The priming lever 216 is biased towards a radially outward position via the biasing member 284. Thus, the priming lever 216 in FIGS. 6-11 is shown in a “squeezed” position (e.g., wherein a user forces the priming lever 216 radially inward against the force of the biasing member 284). In the squeezed position, the priming lever 216 moves the priming bar 280 “backward” towards the proximal end 212 of the handle 210.

[0090] Movement of the priming lever 216 radially inwards, and corresponding movement of the priming bar 280 towards the proximal end 212 of the handle 210, moves the deployment mechanism into the “primed” position. Specifically, an opening in the priming bar 280 engages with the locking protrusion 266 to move the first hub 260 backward. The first pivoting snap-fit 268 is biased (e.g., via a torsion spring) so that a distal locking end thereof is biased radially inward. The distal end of the first pivoting snap-fit 268 snaps onto the priming protrusion 264, locking the first hub 260 in the primed position. In a similar manner, an opening in the priming bar 280 engages with the locking protrusion 276 to move the second hub 270 backward. The second pivoting snap-fit 278 is biased (e.g., via torsion spring) so that a distal locking end thereof is biased radially inward. The distal end of the second pivoting snap-fit 278 snaps onto the priming protrusion 274, locking the second hub 270 in the primed position.

[0091] The priming lever 216 may be moved in a two-stage process so that squeezing the priming lever 216 once primes the first hub 260, and squeezing the priming lever 216 a second time primes the second hub 270. Such an arrangement is enabled by the structure and movement of the priming bar 280, which may move radially inward and outward in addition to moving longitudinally forward and backward. For example, squeezing the priming lever 216 radially inward may move the priming bar 280 radially inward so that the priming protrusion 264 of the first hub 260 and the priming protrusion 274 of the second hub 270 extend through corresponding openings in the priming bar 280. A proximal end of the priming bar 280 is disposed further radially away from the longitudinal axis 201 compared to a distal end of the priming bar 280, enabling one of the openings in the priming bar to “miss” one of the priming protrusions as the priming bar 280 moves towards the proximal end 212 of the handle 210 during a first or second priming operation. However, in other implementations, the priming lever may engage with and prime both of the hubs in a single action.

[0092] The trigger 218 on the second side of the handle 210 is coupled to a trigger bar 286 that extends longitudinally along the inner cavity 252. The trigger 218 and the trigger bar 286 are biased towards the proximal end 212 of the handle 210 and are slidable towards the distal end 214 of the handle 210.

[0093] Once the first hub 260 and the second hub 270 are in the primed position, movement of the trigger 218 in the deployment or firing direction initiates deployment of the stylet 230 and the cannula 220. Specifically, a sloped protrusion 288 on the proximal end of the trigger bar 286 extends radially inward from the trigger bar 286. The sloped protrusion 288 engages with a proximal end of the first pivoting snap-fit 268 to rotate the first pivoting snap-fit 268 against its biased direction. Once rotated far enough, the first pivoting snap-fit 268 releases the first hub 260, starting the deployment process.

[0094] When deployed, the biasing member 262 urges the released first hub 260 in the deployment or firing direction, which correspondingly deploys the stylet 230 in the distal direction. The first hub 260 then abuts the follower 256. The distal surface of the follower 256 engages with the second pivoting snap-fit 278 in a similar manner to the sloped protrusion 288 of the trigger bar 286. The second pivoting snap-fit 278 is rotated to release the second hub 270, which is urged in the deployment or firing direction by the biasing member 272. The cannula 220 is correspondingly deployed in the distal direction. Thus, the chain reaction of the stylet 230 and cannula 220 deployment is initiated by the movement of the trigger 218.

[0095] The handle 210 further includes a sheath retractor 290 on the distal end 214 of the handle 210. The sheath retractor 290 is coupled to the protective sheath 240 to move the protective sheath 240 in a longitudinal direction. The sheath retractor 290 includes a locking member 292 coupled to and extending from the protective sheath 240 in a transverse direction (e.g., perpendicular to the longitudinal axis 201 in a radially outward direction).

[0096] The sheath retractor 290 further defines one or more locking slots 294 extending radially through the sheath retractor 290. The one or more locking slots 294 are configured to engage the locking member 292 and retain the protective sheath 240 in one of a deployed position or a retracted position. For example, a distally located slot of the one or more locking slots 294 may be used for the retracted position, and a proximally located slot of the one or more locking slots 294 may be used for the deployed position of the protective sheath 240.

[0097] FIGS. 12-16 show various views of the distal end 204 of the tissue sampling device 200, including the cannula 220, the stylet 230, and the protective sheath 240. In general, the cannula 220, the stylet 230, and the protective sheath 240 are each flexible along their lengths to navigate a luminal organ (e.g., a ureter). Each of the cannula 220, the stylet 230, and the protective sheath 240 are insertable into a lumen of an endoscope to facilitate navigation to a target tissue (e.g., a tumor). Each of the cannula 220, the stylet 230, and the protective sheath 240 are capable of curling in a variety of desired angles and orientations to facilitate navigation (e.g., as an end effector).

[0098] The cannula 220 of the tissue sampling device 200 defines a lumen 222. The cannula 220 includes a proximal end coupled to the second hub 270 and a distal end opposite and spaced apart from the proximal end along the longitudinal axis 201. The cannula 220 is a flexible outer shell or tube that is bendable to controllably conform to the anatomy of the living subject (e.g., the pathway of the ureter of a living subject). The distal end of the cannula 220 includes a cutting edge 224. For example, the cannula 220 may include a beveled cutting edge 224. The cutting edge 224 extends circumferentially around the distal opening of the lumen 222.

[0099] The stylet 230 extends through the lumen 222 defined by the cannula 220. The stylet 230 includes a proximal end coupled to the first hub 260 and a distal end opposite and spaced apart from the proximal end along the longitudinal axis 201. The distal end of the stylet 230 includes a cutting edge 232 (e.g., a beveled cutting edge or an annular-bladed tip) configured to extend into a target tissue of a living subject.

[0100] A specimen notch 234 is defined by the body of the stylet 230. The specimen notch 234 extends in the longitudinal direction and is spaced apart a distance away from the cutting edge 232. The specimen notch 234 may have a radial depth that is half the diameter of the stylet 230. The stylet 230 is configured to extend into a target tissue to collect a specimen or a sample within the specimen notch 234.

[0101] The protective sheath 240 is coupled to the sheath retractor 290 on a proximal end and extends to a distal end along the longitudinal axis 201. The protective sheath 240 of the tissue sampling device 200 defines a second lumen 242. The stylet 230 and the cannula 220 are each disposed within the second lumen 242 and longitudinally movable relative to the protective sheath 240.

[0102] The protective sheath 240 generally provides a protective, flexible layer for the tissue sampling device 200 during insertion and navigation along a luminal organ. The protective sheath 240 may include a flexible plastic material (e.g., PTFE, thermoplastic elastomers, or other flexible, biocompatible plastic material). The protective sheath 240 further includes a tip portion 244 having a relatively more flexible material compared to the rest of the protective sheath 240 such that the tip portion 244 is easily bendable to facilitate insertion and navigation of a luminal organ. In other implementations, the protective sheath is uniformly flexible along its length.

[0103] In use, the distal end 204 of the tissue sampling device 200 is inserted into a living subject (e.g., via a lumen of an endoscope). The protective sheath 240 covers and retains each of the stylet 230 and the cannula 220 as the tissue sampling device 200 is navigated along the luminal organ toward the target tissue. The ends of the protective sheath 240 and / or the cannula 220 are controllable to navigate the narrow anatomy and flexible to prevent unwanted damage to the organ.

[0104] Once the distal end 204 is adjacent to the target tissue, a user (e.g., a healthcare professional) operates the sheath retractor 290 to retract the protective sheath 240. Specifically, the user may rotate the sheath retractor 290 relative to the locking member 292 and then move the handle 210 relative to the sheath retractor 290 in order to move the locking member 292 into a different one or more locking slots 294. The sheath retractor 290 is then rotated to lock the locking member 292 into a different one of the one or more locking slots 294, locking the protective sheath 240 in the retracted position. In the retracted position, the distal end of the protective sheath 240 is either even with, or proximal to, the cutting edge 232 of the stylet 230 such that at least a portion of the stylet 230 is exposed.

[0105] The user may then prime the deployment mechanism by squeezing the priming lever 216 radially inward towards the housing 250. The priming bar 280 is moved backward towards the proximal end 212 of the handle 210 to engage with each of the priming protrusion 264 of the first hub 260 and the priming protrusion 274 of the second hub 270. The first pivoting snap-fit 268 locks onto the priming protrusion 264 of the first hub 260, and the second pivoting snap-fit 278 locks onto the priming protrusion 274 of the second hub 270, locking each of the first hub 260 and the second hub 270 in the primed position. In some implementations, the priming operation is performed before the tissue sampling device 200 is inserted into the subject. In some implementations, two priming operations may be performed to prime the hubs one at a time. In some implementations, one priming operation is performed to prime both hubs at once.

[0106] When the cutting edge 232 of the stylet 230 is in position adjacent to the target tissue, and when the deployment mechanism of the handle 210 is in the primed position, the user may actuate the trigger 218. By moving the trigger 218 and the trigger bar 286 coupled thereto in the deployment direction (i.e., towards the distal end 214 of the handle 210), the sloped protrusion 288 engages with the first pivoting snap-fit 268. The first pivoting snap-fit 268 rotates to release the first hub 260, which is fired “forward” in the deployment direction by the force of the biasing member 262. The stylet 230 is forced by the first hub 260 into the target tissue such that a portion of the target tissue is disposed within the specimen notch 234. The distance that the stylet 230 is fired corresponds to the distance that the first hub 260 moves within the inner cavity 252. Thus, the handle 210 may further define one or more mechanical stops within the inner cavity 252 to limit the travel distance for the first hub 260. In some examples, the desired core biopsy depth and the corresponding movement distance of the first hub 260 is in a range of 0.3 cm to 3 cm (e.g., 0.5 cm, 1 cm, or 2 cm).

[0107] Directly after the first hub 260 is deployed, the follower 256 is forced forward into the second pivoting snap-fit 278. The second pivoting snap-fit 278 then rotates to release the second hub 270, which is also fired forward in the deployment direction by the force of the biasing member 272. The cannula 220 is forced by the second hub 270 into the target tissue around the specimen notch 234 and the stylet 230. Thus, the cutting edge 224 of the cannula 220 removes and retains the core biopsy sample within the specimen notch 234. The distance that the cannula 220 is fired corresponds to the distance that the second hub 270 moves within the inner cavity 252. Thus, the handle 210 may further define one or more mechanical stops within the inner cavity 252 to limit the travel distance for the second hub 270.

[0108] The user then rotates and moves the sheath retractor 290 such that the protective sheath 240 is moved longitudinally back to the deployed position. The protective sheath 240 further protects and isolates the collected core biopsy sample. The tissue sampling device 200 is then removed from the luminal organ and the living subject for collection and analysis.

[0109] Although specific structures for deployment are shown in FIGS. 6-16, they are exemplary only and do not limit the scope of the disclosure. In other implementations, the housing of the handle may include a different shape and / or may include ergonomically placed gripping surfaces. In other implementations, the priming lever may have a different shape or orientation.

[0110] In other implementations, a different actuation mechanism may be used for priming the hubs (e.g., a button, knob, dial, toggle switch, slide lock, or other common mechanical activation structures). In other implementations, the trigger may include alternative actuation mechanisms (e.g., a button, lever, knob, dial, toggle switch, slide lock, or other common mechanical activation structures). In other implementations, additional safety features or two-step operations may be included to prevent premature deployment (e.g., a two-button trigger mechanism).Conclusion[OHl] For purposes of this description, certain advantages and novel features of the aspects and configurations of this disclosure are described herein. The described methods, systems, and apparatus should not be construed as limiting in any way. Instead, the present disclosure is directed toward all novel and nonobvious features and aspects of the various disclosed aspects, alone and in various combinations and sub-combinations with one another. The disclosed methods, systems, and apparatus are not limited to any specific aspect, feature, or combination thereof, nor do the disclosed methods, systems, and apparatus require that any one or more specific advantages be present or problems be solved.

[0112] Although the figures and description may illustrate a specific order of method steps, the order of such steps may differ from what is depicted and described, unless specified differently above. Also, two or more steps may be performed concurrently or with partial concurrence, unless specified differently above. Such variation may depend, for example, on the software and hardware systems chosen and on designer choice. All such variations are within the scope of the disclosure. Likewise, software implementations of the described methods could be accomplishedwith standard programming techniques with rule-based logic and other logic to accomplish the various connection steps, processing steps, comparison steps, and decision steps.

[0113] Features disclosed in this specification (including any accompanying claims, abstract, and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. The claimed features extend to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract, and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0114] As used in the specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another aspect includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about”, it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. The terms “about” and “approximately” are defined as being “close to” as understood by one of ordinary skill in the art. In one non-limiting aspect the terms are defined to be within 10%. In another non-limiting aspect, the terms are defined to be within 5%. In still another non-limiting aspect, the terms are defined to be within 1%.

[0115] The terms “coupled”, “connected”, and the like as used herein mean the joining of two members directly or indirectly to one another. Such joining may be stationary (e.g., permanent) or moveable (e.g., removable or releasable). Such joining may be achieved with the two members or the two members and any additional intermediate members being integrally formed as a single unitary body with one another or with the two members or the two members and any additional intermediate members being attached to one another. If “coupled” or variations thereof are modified by an additional term (e.g., directly coupled), the generic definition of “coupled” provided above is modified by the plain language meaning of the additional term (e.g., “directly coupled” means the joining of two members without any separate intervening member), resulting in a narrower definition than the generic definition of “coupled” provided above. Such coupling may be mechanical, electrical, or fluidic.

[0116] Certain terminology is used in the following description for convenience only and is not limiting. The words “right”, “left”, “lower”, and “upper” designate direction in the drawings to which reference is made. The words “inner” and “outer” refer to directions toward and away from, respectively, the geometric center of the described feature or device. The words “distal” and “proximal” refer to directions taken in context of the item described and, with regard to the instruments herein described, are typically based on the perspective of the practitioner using such instrument, with “proximal” indicating a position closer to the practitioner and “distal” indicating a position further from the practitioner. The terminology includes the above-listed words, derivatives thereof, and words of similar import.

[0117] Throughout the description and claims of this specification, the word “comprise” and variations of the word, such as “comprising” and “comprises”, means “including but not limited to”, and is not intended to exclude, for example, other additives, components, integers or steps. “Exemplary” means “an example of’ and is not intended to convey an indication of a preferred or ideal aspect. “Such as” is not used in a restrictive sense, but for explanatory purposes.

[0118] The corresponding structures, materials, acts, and equivalents of all means or step plus function elements in the claims below are intended to include any structure, material, or act for performing the function in combination with other claimed elements as specifically claimed. The description of the present disclosure has been presented for purposes of illustration and description but is not intended to be exhaustive or limited to the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the present disclosure.

Claims

What is claimed is:

1. A tissue sampling device comprising: a handle comprising a deployment mechanism; a cannula insertable into an endoscopic lumen of an endoscope, the cannula having a proximal end coupled to a first portion of the deployment mechanism and a distal end spaced apart from the handle along a longitudinal axis, the cannula defining a first lumen extending from the proximal end to the distal end of the cannula; and a stylet disposed within the first lumen, the stylet having a proximal end coupled to a second portion of the deployment mechanism and a distal end spaced apart from the handle along the longitudinal axis, wherein the stylet comprises a cutting edge on the distal end and defines a specimen notch spaced from the cutting edge on the distal end of the stylet, wherein each of the stylet and the cannula are independently movable in a longitudinal direction with respect to each other and are deployable in the longitudinal direction by the deployment mechanism, wherein each of the stylet and the cannula is flexible along its length.

2. The tissue sampling device of claim 1, further comprising: a protective sheath having a proximal end coupled to a third portion of the handle and a distal end spaced apart from the handle along the longitudinal axis, the protective sheath defining a second lumen extending from the proximal end to the distal end of the protective sheath, wherein the stylet and the cannula are both disposed within the second lumen and independently movable in the longitudinal direction with respect to the protective sheath.

3. The tissue sampling device of claim 2, wherein the protective sheath is flexible along its length, and the distal end of the protective sheath includes a flexible portion being more flexible than the remainder of the protective sheath.

4. The tissue sampling device of claim 3, wherein the deployment mechanism comprises: a sheath retractor on a distal end of the handle, the sheath retractor being rotatable and movable in the longitudinal direction with respect to the handle, the sheath retractor comprising a locking member coupled to and extending transverse from the protective sheath,wherein the sheath retractor defines one or more locking slots configured to engage the locking member and retain the protective sheath in one of a deployed position or a retracted position.

5. The tissue sampling device of claim 1, wherein: a first portion of the deployment mechanism is configured to move the stylet longitudinally with respect to each of the cannula; and a second portion of the deployment mechanism is configured to move the cannula longitudinally with respect to each of the stylet.

6. The tissue sampling device of claim 5, wherein the first portion of the deployment mechanism comprises a first button coupled to a first gear and the second portion of the deployment mechanism comprises a second button coupled to a second gear.

7. The tissue sampling device of claim 5, wherein the deployment mechanism is a spring- loaded deployment mechanism comprising a priming lever and a trigger, wherein the first portion of the deployment mechanism is a first hub coupled to the proximal end of the stylet and the second portion of the deployment mechanism is a second hub coupled to the proximal end of the cannula, wherein each of the first hub and the second hub is biased in an axially forward direction towards the distal end of the stylet and the cannula.

8. The tissue sampling device of claim 7, further comprising: a first snap-fit engageable with the first hub to retain the first hub in a primed position; and a second snap-fit engageable with the second hub to retain the second hub in a primed position.

9. The tissue sampling device of claim 8, wherein the trigger is movable to engage the first snap-fit and release the first hub from the primed position to a deployed position in the longitudinal direction.

10. The tissue sampling device of claim 9, wherein the first hub abuts a follower that is movable to engage the second snap-fit and release the second hub from the primed position to a deployed position.

11. The tissue sampling device of claim 8, wherein the priming lever is coupled to a priming member disposed along the handle adjacent to the first hub and the second hub, wherein the priming lever and the priming member are moveable to push one or both of the first hub and the second hub longitudinally toward the primed position.

12. The tissue sampling device of claim 5, wherein the deployment mechanism deploys the stylet at a speed in the range of 0.5 - 20 m / s.

13. The tissue sampling device of claim 12, wherein the speed is greater than 8 m / s.

14. The tissue sampling device of claim 1, wherein the cutting edge of the stylet is a beveled edge.

15. The tissue sampling device of claim 1, wherein the distal end of the cannula includes a second cutting edge.

16. The tissue sampling device of claim 1, wherein the distal end of the stylet is movable in the longitudinal direction to a first distance from the distal end of the cannula, and the distal end of the cannula is movable to a second distance.

17. The tissue sampling device of claim 16, wherein the first distance is equal to the second distance.

18. The tissue sampling device of claim 16, wherein the first distance is in the range of 2-20 mm.

19. The tissue sampling device of claim 1, wherein the endoscope further comprises a camera on a distal end of the endoscope.

20. The tissue sampling device of claim 1, wherein the distal end of the cannula and the distal end of the stylet are both capable of curling in a variety of desired angles and orientations to facilitate navigation.

21. The tissue sampling device of claim 2, wherein either one of the cannula, the stylet, or the protective sheath has a length from the proximal end to the distal end thereof in the range of 60cm-250cm.

22. The tissue sampling device of claim 21, wherein the length is greater than 115cm.

23. The tissue sampling device of claim 2, wherein either one of the cannula, the stylet, or the protective sheath has a diameter in the range of 2 - 12 Fr (0.67 - 4 mm).

24. The tissue sampling device of claim 23, wherein the diameter is less than 3.5 Fr.

25. A method of collecting a tissue sample, the method comprising: providing a tissue sampling device comprising: a handle comprising a deployment mechanism; a cannula having a proximal end coupled to a first portion of the deployment mechanism and a distal end spaced apart from the handle along a longitudinal axis, the cannula defining a first lumen extending from the proximal end to the distal end of the cannula; and a stylet disposed within the first lumen, the stylet having a proximal end coupled to a second portion of the deployment mechanism and a distal end spaced apart from the handle along the longitudinal axis, wherein the stylet comprises a cutting edge on the distal end and defines a specimen notch spaced from the cutting edge on the distal end of the stylet, inserting the cannula of the tissue sampling device into an endoscopic lumen of an endoscope that extends into a living subject; advancing the cannula until the distal ends of each of the cannula and the stylet are adjacent to a target tissue;activating the first portion of the deployment mechanism to longitudinally extend the distal end of the stylet into the target tissue beyond the distal end of the cannula to expose the specimen notch; activating the second portion of the deployment mechanism to longitudinally extend the distal end of the cannula into the target tissue to contain the specimen notch; and retracting the stylet and the cannula out of the living subject.

26. The method of claim 25, wherein the step of activating the first portion of the deployment mechanism to longitudinally extend the distal end of the stylet comprises cutting a portion of the target tissue with the cutting edge such that a specimen of the target tissue is disposed within the specimen notch.

27. The method of claim 25, wherein the step of activating the second portion of the deployment mechanism to longitudinally extend the distal end of the cannula comprises cutting a portion of the target tissue such that the specimen is removed from the target tissue to be fully retained by the specimen notch and the cannula.

28. The method of claim 25, wherein the target tissue is a tumor or a mass in a hollow viscera or luminal organ.

29. The method of claim 25, wherein the target tissue is a malignancy of a luminal organ.

30. The method of claim 25, further comprising: analyzing the target tissue and grading a cancer type of the target tissue.

31. The method of claim 25, wherein the tissue sampling device further comprises: a protective sheath having a proximal end coupled to a third portion of the handle and a distal end spaced apart from the handle along the longitudinal axis, the protective sheath defining a second lumen extending from the proximal end to the distal end of the protective sheath, wherein the stylet and the cannula are both disposed within the second lumen and independently movable in a longitudinal direction with respect to the protective sheath.

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