RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62/471,035, filed March 14, 2017, the entirety of which is hereby incorporated by reference for all purposes.

STATEMENT OF GOVERNMENT SUPPORT

[0002] This invention was made with government support under FA8650-15-C-7548 awarded by the Defense Advanced Research Projects Agency (DARPA). The government has certain rights in the invention.

FIELD

[0003] The present disclosure relates to systems and methods for retracting tissue during medical procedures, including endoscopic procedures.

BACKGROUND

[0004] Current trends in surgical procedures have focused on minimally invasive surgery (MIS) with the end goal of shortening recovery time and improving patient outcomes. Since their development in the 1960s, flexible and steerable endoscopes have become the standard approach for diagnostic and therapeutic procedures in the gastrointestinal (GI) tract. Although endoscopic diagnostic procedures performed are well-established and routine, many challenges exist when using endoscopes for therapeutic procedures, such as excising or ablating cancerous sites or other lesions. These challenges include distal tip instability, a lack of control for fine distal positioning, and the low amount of force that can be exerted by the endoscope tip without causing deflection of the endoscope itself. Techniques such as endoscopic submucosal dissection (ESD) have been developed to help address these shortcomings, but they require extensive training to successfully perform. Endoscopic mucosal resection (EMR) is another procedure aimed at removing small lesions (< 25 mm) in the GI tract, but is challenged by the lack of endoscope distal tip dexterity. Additional research has included the development of endoscopic add-ons to supplement the existing capabilities of conventional endoscopes, but these are similarly hampered by the inherent flexibility of the endoscope. Although this flexibility is crucial for navigating the curving GI tract to reach the surgical site, the flexibility of the distal tip of the endoscope limits the capabilities of endoscopic therapeutic procedures. Proposed solutions of anchoring the endoscope are numerous in the literature, with examples including inflatable balloons, pop-up structures, and adhesives. Work has also been done to enhance distal tip dexterity with a highly-controllable means of steering the endoscope tools, minimizing the need to move the endoscope itself.

SUMMARY

[0005] Systems and methods for pop-up tissue retraction are disclosed. A tissue retraction device is provided, and includes a tissue retraction mechanism configured to anchor and retract a tissue to be manipulated, and at least one actuator associated with the tissue retraction mechanism. The at least one actuator is configured to move between an unexpanded state such that the tissue retraction mechanism can adhere to the tissue, and an expanded state such that the tissue retraction mechanism applies a force to the tissue to anchor the tissue and cause retraction thereof.

[0006] In some embodiments, the tissue retraction mechanism is in the form of a vacuum gripper. In some embodiments, the at least one actuator comprises a first actuator and a second actuator. The first actuator and the second actuator can be in the form of bellows. The tissue retraction mechanism is positioned between the first actuator and the second actuator. In some embodiments, the at least one actuator is in the form of at least one multistage actuator having a rigid portion between each stage of the multi-stage actuator.

[0007] In some embodiments, the tissue retraction mechanism includes at least a rigid portion configured to provide structural support to the at least one actuator in the expanded state. The rigid portion can be in the form of a folding structure that is configured to unfold upon deployment of the at least one actuator into the expanded state. In some embodiments, the tissue is manipulated by a medical device that extends from a distal end of an endoscopic device.

[0008] An endoscopic device can also be provided, and can include an elongate body having a lumen extending therethrough such that at least one tissue manipulation instrument can be passed therethrough for manipulating tissue at a distal end of the elongate body, and a tissue retraction device coupled to an outer surface of the elongate body configured to anchor and retract tissue such that tissue grasping is decoupled from movement of the endoscopic device during manipulation of the tissue. The tissue retraction device comprises a tissue retraction mechanism configured to anchor and retract a tissue to be manipulated during a procedure using the endoscopic device, and at least one actuator configured to move between an unexpanded state such that the tissue retraction mechanism can adhere to the tissue, and an expanded state such that the tissue retraction mechanism applies a force to the tissue and cause retraction thereof.

[0009] In some embodiment, the endoscopic device can further comprise a hollow overtube. The endoscopic device can be positioned within the hollow overtube such that the tissue retraction device can be deployed when the hollow overtube is retracted from the endoscope to expose the tissue retraction device.

[0010] In some embodiments, the tissue retraction mechanism is in the form of a vacuum gripper. In some embodiments, the at least one actuator comprises a first actuator and a second actuator. The tissue retraction mechanism can be positioned between a first actuator and a second actuator. In some embodiments, the tissue retraction device includes at least a rigid portion configured to provide structural support to the at least one actuator in the expanded state.

[0011] A method of performing tissue retraction is also provided, comprising deploying a tissue retraction device from an outer surface of an elongate body of an endoscopic device such that the tissue retraction device is positioned adjacent to a target tissue to be retraction and manipulated by the endoscopic device, and anchoring the tissue retraction mechanism to the target tissue using a tissue retraction mechanism. At least one actuator coupled to the tissue retraction mechanism is deployed from an unexpanded state during which the tissue retraction mechanism anchors the target tissue into an expanded state such that the tissue retraction mechanism applies a force to the target tissue to cause retraction of the target tissue.

[0012] In some embodiments, deploying the at least one actuator allows for the at least one actuator to expand from an initial height in the unexpanded state to an expanded height in the expanded state such that the target tissue is retracted to substantially the expanded height of the least one actuator. For example, the expanded height allows for one or more tools extending through the elongate body of the endoscopic device to access the target tissue. In some embodiments, the at least one actuator is in the form of first and second actuators such that the first and second actuators provide balanced support for the tissue retraction mechanism to anchor to the target tissue and retract the target tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The present disclosure is further described in the detailed description which follows, in reference to the noted plurality of drawings by way of non-limiting examples of exemplary embodiments, in which like reference numerals represent similar parts throughout the several views of the drawings, and wherein:

[0014] FIG. 1A, FIG. IB, FIG. 1C, and FIG. ID illustrate an embodiment of a tissue retraction device in use with an endoscope;

[0015] FIG. 2A, FIG. 2B, FIG. 2C, and FIG. 2D illustrate an exemplary fabrication workflow for an embodiment of a bellows actuator;

[0016] FIG. 3A is an embodiment of a bellows actuator;

[0017] FIG. 3B is an embodiment of a vacuum gripper;

[0018] FIG. 3C is an embodiment of a MEMS structure;

[0019] FIG. 3D is an embodiment of a tissue retraction device in an undeployed state;

[0020] FIG. 3E is the tissue retraction device of FIG. 3D is an expanded state;

[0021] FIG. 4 is an exemplary graph of pressure versus force for an embodiment of a bellows actuator;

[0022] FIG. 5 is an exemplary graph of displacement versus pressure during inflation of an embodiment of a bellows actuator;

[0023] FIG. 6 is an exemplary graph of pressure versus force for an embodiment of a bellows actuator in retraction;

[0024] FIG. 7A illustrates an embodiment of an actuator undergoing buckling;

[0025] FIG. 7B illustrates an embodiment of an actuator with a rigid internal disk that is configured to resist buckling;

[0026] FIG. 8A, FIG. 8B, FIG. 8C, and FIG. 8D illustrate an embodiment of a tissue retraction device in use; and

[0027] FIG. 9 illustrates an embodiment of a tissue retraction device deployed on target tissue. [0028] While the above-identified drawings set forth presently disclosed embodiments, other embodiments are also contemplated, as noted in the discussion. This disclosure presents illustrative embodiments by way of representation and not limitation. Numerous other modifications and embodiments can be devised by those skilled in the art which fall within the scope and spirit of the principles of the presently disclosed embodiment.

DETAILED DESCRIPTION

[0029] The following description provides exemplary embodiments only, and is not intended to limit the scope, applicability, or configuration of the disclosure. Rather, the following description of the exemplary embodiments will provide those skilled in the art with an enabling description for implementing one or more exemplary embodiments. It will be understood that various changes may be made in the function and arrangement of elements without departing from the spirit and scope of the presently disclosed embodiments.

[0030] Specific details are given in the following description to provide a thorough understanding of the embodiments. However, it will be understood by one of ordinary skill in the art that the embodiments may be practiced without these specific details. For example, systems, processes, and other elements in the presently disclosed embodiments may be shown as components in block diagram form in order not to obscure the embodiments in unnecessary detail. In other instances, well-known processes, structures, and techniques may be shown without unnecessary detail in order to avoid obscuring the embodiments.

[0031] Also, it is noted that individual embodiments may be described as a process which is depicted as a flowchart, a flow diagram, a data flow diagram, a structure diagram, or a block diagram. Although a flowchart may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently. In addition, the order of the operations may be re-arranged. A process may be terminated when its operations are completed, but could have additional steps not discussed or included in a figure. Furthermore, not all operations in any particularly described process may occur in all embodiments. A process may correspond to a method, a function, a procedure, a subroutine, a subprogram, etc. When a process corresponds to a function, its termination corresponds to a return of the function to the calling function or the main function.

[0032] Subject matter will now be described more fully with reference to the accompanying drawings, which form a part hereof, and which show, by way of illustration, specific example aspects and embodiments of the present disclosure. Subject matter may, however, be embodied in a variety of different forms and, therefore, covered or claimed subject matter is intended to be construed as not being limited to any example embodiments set forth herein; example embodiments are provided merely to be illustrative. The following detailed description is, therefore, not intended to be taken in a limiting sense.

[0033] In general, terminology may be understood at least in part from usage in context. For example, terms, such as "and", "or", or "and/or," as used herein may include a variety of meanings that may depend at least in part upon the context in which such terms are used. Typically, "or" if used to associate a list, such as A, B, or C, is intended to mean A, B, and C, here used in the inclusive sense, as well as A, B, or C, here used in the exclusive sense. In addition, the term "one or more" as used herein, depending at least in part upon context, may be used to describe any feature, structure, or characteristic in a singular sense or may be used to describe combinations of features, structures or characteristics in a plural sense. Similarly, terms, such as "a," "an," or "the," again, may be understood to convey a singular usage or to convey a plural usage, depending at least in part upon context. In addition, the term "based on" may be understood as not necessarily intended to convey an exclusive set of factors and may, instead, allow for existence of additional factors not necessarily expressly described, again, depending at least in part on context.

[0034] Numerous therapeutic transendoscopic procedures exist to treat lesions in the GI tract. However, these procedures are limited by their difficulty and the amount of training required to successfully perform them. The surgeon is tasked with simultaneously steering the distal tip of the endoscope, applying tension to tissue to retract it, and manipulating electro-cautery tools with limited dexterity. In some embodiments, a device can be used to assist with anchoring and tissue retraction during endoscopic surgical procedures, which can decouple the tissue grasping function from the movement of the endoscope tip, leaving the surgeon free to use the endoscope tip solely for positioning of electro-cautery or biopsy tools deployed through the endoscope working channel. The anchoring and retraction device uses pop-up book MEMS techniques, allowing for a flat structure to expand into a 3 -dimensional structure many times its initial height. In some embodiments, the device has three main integrated components: a rigid expandable geometric structure, one or more inflatable pneumatic actuators, and a tissue retraction mechanism, such as a vacuum gripper. These inflatable actuators include internal rigid discs, allowing for resistance to buckling while maintaining the benefits of the established lightweight, low profile actuator design scheme. Proof-of concept ex vivo testing demonstrates that the integrated device can be used to retract tissue to a height of 13.5 mm, providing access for endoscopy tools to contact a sample of porcine stomach tissue.

[0035] In some embodiments, a tissue retraction device is a deployable device that can be fully detached and independent from movement of an endoscope. Using a tissue retraction device, the tissue-grasping function is decoupled from the movement of the endoscope tip, leaving the surgeon free to use the endoscope tip solely for positioning of electro-cautery or biopsy tools deployed through the endoscope working channel. In an embodiment, the anchoring and retraction device uses "pop-up book MEMS" techniques, allowing for a "flat" structure to expand into a 3-dimensional structure many times its initial height.

[0036] FIG. 1A, FIG. IB, FIG. 1C, and FIG. ID illustrate an embodiment of a device and the workflow for deployment and tissue retraction using a tissue retraction device. FIG. 1A illustrates an embodiment of a collapsed tissue retraction device 10 affixed to an endoscope 12 within a hollow overtube 14. FIG. IB illustrates the deployment of the tissue retraction device 10 by retracting the overtube 14 to expose the device 10. FIG. 1C illustrates the device 10 being positioned over the targeted tissue 18, such as a lesion. In the illustrated embodiment, the device 10 is positioned over the targeted tissue 18 with the use of a tool, such as forceps 20, extending from a distal end of the endoscope 12. FIG. ID illustrates a mechanism for retracting tissue, allowing conventional tools, such as an electro-cautery tool 22, to be used to excise the lesion with electro-cautery. As shown in FIG. ID, the device 10 is used to retract the targeted tissue 18 (the lesion).

[0037] There are many limitations of current resection or ablation-based surgical procedures targeting early colorectal cancer (ECC) lesions in the lower GI tract performed with conventional flexible endoscopes. In order to fit within the current work-flow of therapeutic endoscopic procedures, in some embodiments, a tissue retraction device can be introduced into the body along the outside of the distal end of an endoscope 12 and encased in a retractable overtube 14 (as shown in FIG. 1A, FIG. IB, FIG. 1C, and FIG. ID). By automating the act of placing tissue under tension and decoupling this action from the motion of the endoscope tip, the integrated device has the potential to expand surgeons' capabilities and increase the number of surgeons capable of performing these types of procedures.

[0038] In some embodiments, a tissue retraction device can be affixed to the outside surface of the distal end of an endoscope and constrained within an overtube to shield the device from contacting tissue until at the surgical site in the GI tract, as shown in FIG. 1A. The overtube is then retracted to expose the device (FIG. IB). Forceps deployed through the endoscope working channel are used by the surgeon to position the device atop a lesion, with visual guidance and confirmation from the illuminated distal camera (FIG. 1C). Although shown placing the device on a horizontal section of tissue, because it is grasped by forceps during positioning, the distal endoscope position and orientation can be adjusted by the surgeon to place the device in the GI tract regardless of orientation to horizontal. Once properly positioned, negative pressure is applied to the vacuum gripper at the center of the device, adhering the device to the lesion site while negative pressure is sustained. The dual bellows actuators are then inflated, expanding the pop-up structure and retracting the grasped tissue. The surgeon can now use conventional endoscopy tools such as electro-cautery probes inserted through the endoscope working channel to cut through the mucosa and muscularis layers beneath the lesion site, as shown in FIG. ID. The dissected tissue can still be held by the device's vacuum gripper and can be grasped with forceps for removal from the body for pathology analysis. The device is rapidly collapsed by venting pressure from the bellows actuators. To excise larger lesions, the tissue retraction device can be repeatedly expanded, collapsed, and repositioned with forceps delivered through the endoscope working channel to adjust vacuum gripper location between rounds of electro-cautery. To remove the device from the body upon completion of a procedure, negative pressure is applied to the bellows actuators to keep them in a deflated state, the overtube is advanced, and forceps are used to maneuver the device back into the overtube while the endoscope is retracted. The thickness of the device before inflation should add less than 10 mm to the endoscope diameter to maintain overtube compatibility, and the device requires an expanded height of 13 mm or greater to retract tissue to a height of 10 mm, which offers sufficient access to the retracted tissue by endoscope end effectors. However, the fabrication workflow presented here could be customized for different actuator use cases. It will be understood that the tissue retraction device can be delivered to the target tissue in a variety of ways, including but not limited to delivering the tissue retraction device through the working channel of the endoscope, as long as the tissue retraction tissue is sized and shaped to fit therein.

[0039] The soft actuator of the tissue retraction device can have many configurations. In some embodiment, the soft actuators are in the form of bellows. First and second bellows actuators 62, 64, which can include internal rigid PTFE disks, and a vacuum gripper 66 are incorporated into the pop-up structure to complete the tissue retraction device 60, as shown in FIG. 3D and FIG. 3E. The vacuum gripper 66 is mechanically constrained between two layers of fiberglass-epoxy laminate sheets. The bellows actuators 62, 64 are affixed on the top and bottom TPE layers with the same adhesive sheet. Input tubing lines for the bellows actuators are linked together by a tee-fitting to operate from a single input pressure line.

[0040] A variety of fabrication techniques can be used to form a tissue stabilization device. In some embodiments, a fabrication scheme for embedding rigid disks in TPE bellows actuators can be used, with planar manufacturing techniques. Fabrication of an integrated device consisting of an expandable structure, inflatable bellows actuators, and a vacuum gripper to enable tissue retraction is also introduced. The expandable structure is based upon a pop-up book MEMS fabrication methodology. Pop-up book MEMS has been used successfully for the development of medical devices in the literature. The concept of integrating soft, inflatable devices with expandable rigid structures to constrain the inflation of the actuator has also been previously proposed. The integrated device and its components are tested with protocols presented, as discussed below, and the results of these experiments are presented.

[0041] Various methods can be used to form the soft actuators, for example, the bellows actuators. In some embodiments, heat- and pressure-bonded Thermoplastic Elastomer, TPE (Fiber Glast, USA) bellows actuators with Polytetrafluoroethylene (PTFE) mask layers can be used that demonstrate a linear relationship between blocked force and input pressure at low displacement heights, but exert limited retractive forces due to the tendency of bellows chambers to buckle inwards when vacuum is applied, rather than move axially.

In some embodiments, rigid PTFE disks can be introduced within the enclosed chambers of the soft bellows actuators at the same scale. The planar fabrication method of combining subunits to form complete bellows chambers enables the inclusion of additional bellows chambers and thus customizable inflation height. The diameter of the bellows actuators and the number of bellows chambers can vary. In some embodiments, bellows actuators can have with a diameter of 9 mm and four bellows chambers. These dimensions were selected for suitability for integration into the tissue retraction device and limits on overtube size. It will be understood that the size and number of chambers can vary depending on the application and size of the endoscope and overtube. In some embodiments, each chamber of the bellows is approximately 9 mm. The technology can be easily scalable up (larger sizes) or down. For example, it can be scaled down to a few millimeters using the process described herein. In some embodiments, endoscopes can be in the range of 12-18 mm, and the actuators can be designed accordingly.

[0042] In some embodiments, soft actuators can be fabricated with 50 μηι thick Thermoplastic Elastomer - TPE following a 2D layer-by-layer manufacturing process. Different layers of TPE are laser cut with a C02 laser and alternated with laser cut 50 μηι thick Teflon layers o be selectively bonded. Layers of TPE and Teflon are aligned using precision dowel pins. Bonding is achieved by heating the laminate, for example, at 190 °C for one hour under 0.7MPa pressure. This manufacturing technique can be used to fabricate an integrated device consisting of an expandable rigid structure, inflatable bellows actuators, and a vacuum gripper to enable tissue retraction.

[0043] In some embodiments, the first sub-unit of a soft bellows actuator is fabricated with two adjacent layers of 38 μιτι thick TPE following the process shown in FIG. 2A, FIG. 2B, FIG. 2C, and FIG. 2D. This double layer of TPE enhances robustness of the material when undergoing deformation during heating, as this deformation is required to accommodate internal disks of sufficient thickness to resist buckling under applied negative pressure. Different layers of TPE are cut with a C02 laser cutter and alternated with laser-cut 254 μιτι and 76.2 μιτι PTFE layers to act as masks and forms. Layers of TPE and PTFE are aligned using precision dowel pins and stacked manually. The layers of TPE in the first two steps of the process are bonded at 180°C for one hour under 0.07 MPa pressure, as shown in FIG. 2A and FIG. 2B. The 76.2 μπι PTFE layers serve in the first step to mask the TPE and allow only desired areas to bond (FIG. 2A). This first step produces the layer that interfaces between two bellows chambers. The 254 μιτι PTFE also serves as a mask to the TPE but also as a form to create sufficient vertical space while the TPE is heated to encase rigid PTFE disks within the bellows chambers.

[0044] FIG. 2A, FIG. 2B, FIG. 2C, and FIG. 2D illustrate an embodiment of a fabrication workflow for bellows actuators 30 with internal rigid disks. FIG. 2A illustrates an interface layer 32 between adjacent bellows chambers 30, 34. FIG. 2B illustrates additional mold layers with the result of the previous step, creating a pocket for an enclosed disk. FIG. 2C illustrates a final bonding of a top TPE layer 38 and an input tubing 40. FIG. 2D illustrates an example of the dimensions of the enclosed disk. For example, a and b can be 2mm and 8mm, respectively. In some embodiment, b can range from 5mm to 15mm. It will be understood that the dimensions of the disk, and other features of the actuators, can vary depending on a variety of factors, including but not limited to the size of the endoscope and the location of size of the target tissue.

[0045] During the second step of the process (FIG. 2B), multiple subunits resulting from the first step can be added, serving to customize expanded height of the finished actuator. It will be understood that any number of units can be added to the soft actuators depending on the desired height of the actuator in the expanded state. For example, additional 254 μιτι PTFE mold layers are added to transmit the vertically applied force of 0.07 MPa to the areas of TPE being bonded. In this step, the bonds around the outer diameter of all bellows chambers except that with the inlet tubing are formed. Following heat- and pressure-bonding, the top layers of this laminate are manually removed, and additional 254 μιτι PTFE layers are added as forms to create bonds that will enclose the last bellows chamber with its inlet tubing. A tube with internal diameter of 0.64 mm (for example, Micro Renathane Cather Tubing, Braintree Scientific, USA) is inserted and a drop of Loctite Vinyl, Fabric & Plastic Flexible Adhesive is added before the top sheet of TPE and an upper PTFE mold layer are added. The resulting laminate is heated at 145°C for one hour under 0.06 MPa pressure, as shown in FIG. 2C. The external PTFE layers are manually cut away before the laminate has cooled, and the inlet tubing is trimmed, producing a bellows actuator 50 shown in FIG. 3A.

[0046] The output force of an actuator produced from this process can be modeled by the simple F = P x A relationship, where F is the force produced, P is the input pressure, and A is the area of the circular bellows chamber when flat, as determined by the 254 μιτι PTFE layers that transmit the applied force during heating in FIG. 2B and FIG. 2C. This relationship holds true when expanding from flat, with decreased force output as the overall height increases and the TPE begins to strain. However, as this outputted force magnitude diminishes, AF = ΔΡ x A is a better description. The rate at which force output increases with an increase in pressure will be relatively constant and dependent upon the area of a bellows chamber, and is detailed below.

[0047] The presently disclosed embodiments make it possible to fabricate a soft actuator that is less susceptible to bending and/or buckling when under pressure. Previous iterations of soft bellows actuators fabricated with a 76.2 μιτι PTFE film disk encased in each bellows chamber (solely to mask the TPE layers from bonding in the chamber) were susceptible to bending and buckling when under applied negative pressure, limiting the pulling force output to 0.50N. Bellows actuators under retraction also undergo a time dependent decay in applied force as they approach a steady-state constant output, for example, when the TPE and 76.2 μηι PTFE have buckled to their minimum internal volume. Actuators can also be fabricated to prevent time dependent decay.

[0048] As such, in some embodiments, the incorporation of a thicker, more rigid PTFE disk can minimize these effects and improve the retraction performance of the actuator. Modeling the system as a disk under uniform radial compression, which the TPE would apply to the disk under applied negative pressure, as discussed in Eqn. 1 , supports this.

[0049] In some embodiments, the enclosed disk can be in the form of a circular plate with a concentric hole under uniform radial compression on its outer edge, with a being outside diameter of the disk, b being the inner diameter of the disk as shown in FIG. 2D, t being thickness of the disk, E being Young's modulus, υ being Poisson's ratio, and σ' being critical unit compressive stress. Because the ratio of diameter to thickness - is greater than 10, this model holds and it is true that:

where K is a tabulated value dependent upon ^ and equal to a linearly interpolated value of 0.285, thus σ' oc t ² .

[0050] Therefore, increasing the thickness of the internal PTFE disks, for example from 76.2 μηι (solely to mask the TPE) to a thicker sheet (to provide rigidity as well as to act as a mask) increases the bending stiffness of a chamber of the bellows actuator by (t _t hick/tthin) ² ■ For example, when increasing disk thickness from 76.2 μηι to 254 μιτι, this results in increased resistance to buckling by a factor of 3.32, or 10.89.

[0051] This assumes both versions are subjected to the same radial compression, as both are tested under equal vacuum line pressure applied to actuators that are identical other than thickness of their enclosed disks. A thicker internal disk, then, will allow individual bellows actuator chambers to resist subsequent buckling under vacuum and therefore allows higher retractive forces to be achieved.

[0052] In order to integrate the vacuum gripper into the laminar fabrication methodology of the popup structure, the mold is designed to yield a flat sheet of cast elastomer at the top of the vacuum gripper which could be mechanically constrained between two structural sheets with a pass-through for the tubing through which negative pressure is applied. For example, molds are 3D-printed on an SLA Formlabs 2 (Formlabs, Somerville, MA, USA). A silicone elastomer, DragonSkin 20 (Smooth-On, Macungie, PA, USA), is cast into the molds and placed into a vacuum chamber until all trapped air escapes after about ten minutes, before being cured at 60°C for 60 minutes. Individual vacuum grippers are cut apart from the larger array in which they are cast, and a small hole is poked through the top of the cured vacuum gripper. Tubing with internal diameter of 0.64 mm (for example, Micro Renathane Cather Tubing, Braintree Scientific, USA) is inserted and the connection is sealed with additional uncured DragonSkin 20 applied on the interior side of the seal with the vacuum gripper, as shown in FIG. 3B.

[0053] Pop-up book MEMS is a design and fabrication methodology in which thin layers of material are machined individually and selectively laminated together with adhesive and flexible layers, allowing a flat structure to expand into a 3-dimensional device based on flexure joints. In an embodiment, a pop-up structure can be designed to accommodate the incorporation of a vacuum gripper and strain-relieving expandable housing for two bellows actuators, without substantial deformation during use. Materials for the fabrication of the pop-up structure can include but is not limited to 381 mm thick fiberglassepoxy laminate sheets as structural material (Garolite G-10/FR4), 25 μιτι thick polyimide film as flexure layers, and pressure-sensitive 3M sheet adhesive (9877). Each layer is individually machined using a diodepumped solid state (DPSS) laser, and aligned using precision dowel pins. The resulting laminate is laser machined to release the final device structure, shown in FIG. 3C from the bulk substrate before integration of the vacuum gripper. The design of the pop-up structure depends upon the deployment method of the device, in which it is affixed to the outer diameter of the endoscope within a flexible overtube. As such, the pop-up structure is designed to minimize the marginal increase in endoscope diameter before the device is deployed.

[0054] EXPERIMENTS

[0055] All subsystems of the integrated device were tested and characterized individually before incorporation into the integrated device. The soft bellows actuators with rigid internal disks were characterized both in expansion and retraction, a working range of output forces by vacuum suckers was experimentally determined, and the pop-up structure was measured to ensure suitable geometry. Ex vivo tests using porcine stomach were performed to simulate the use of the integrated device in the GI tract. The device was also affixed to an endoscope and a proof-of-concept deployment method was demonstrated. The burst pressure of the actuators was measured by pressuring actuators to failure and was found to be 299 kPa.

[0056] Bellows Actuator Force Characterization

[0057] A four-stage bellows actuator was tested on a materials testing machine (Instron®) by placing it between two flat rigid plates displaced from one another at various discrete heights. Dual syringe pumps provide controllable input pressure measured by a pressure gauge (BSP B010-EV002-A00A0B-S4, Balluff, USA), and force readings from the load cells (Instron® + 10N Static Load Cell, Cat. No: 2530-428) were taken at regular pressure intervals. These values were compared to the theoretical model. The top and bottom layers of TPE were adhered to 254 μηι fiberglass-epoxy laminate sheets with sheets of 3M® 9877 adhesive. This was done to cause a constant area of the TPE pressing against the fiberglass-epoxy laminate, and therefore also the Instron® plate and load cell, regardless of expansion. Without this flat sheet, the contact area decreases as total expansion height increases, as the top bellows chamber does not deform sufficiently to press fully flat against the top plate.

[0058] Bellows actuators were also tested under applied negative pressure to determine the efficacy of the rigid PTFE disks contained within each chamber in resisting buckling and exerting forces under applied negative pressure. The top and bottom layers of TPE were adhered to 254 μιτι fiberglass-epoxy laminate sheets with sheets of 3M® 9877 adhesive, with attached acrylic fixtures to hold these plates in the Instron® jaws. The top and bottom plates were spaced 10 mm apart before negative pressure was applied. Negative pressure was measured using a pressure sensor manifold (MPX4115V, Motorola Freescale Seminconductor, Inc., USA) and the retractive force was measured by the load cell of the Instron®. This test was performed for bellows actuators with internal PTFE disks of 254 μιτι thickness and otherwise identical actuators with 76.2 μιτι internal PTFE disks.

[0059] Vacuum Gripper Testing

[0060] Vacuum grippers cast from silicone elastomers in 3D-printed molds were fixtured in a fiberglass-epoxy and acrylic jig to firmly retain the gripper and affix it to the movable vertical axis of the Instron®. A vacuum was applied (92 kPa) once the base of the vacuum gripper was in contact with a sample of porcine stomach tissue. Once the gripper had retracted a portion of the porcine stomach tissue, the movable plate of the Instron® was raised vertically at a rate of 20 mm/min. Incrementally larger masses of tissue were lifted until the vacuum gripper could no longer fully raise the tissue from its enclosing container.

[0061] Pop-up Structure Testing

[0062] Pop-up structures and their component material selections described above and shown in FIG. 3D and FIG. 3E were evaluated by comparing performance relative to desired expanded height, and desired stiffness of the overall structure. The flexure joints of the mechanism were also evaluated and manually flexed through their full range of motion to ensure sufficient gap distance to prevent the fiberglass-epoxy laminate layers from pinching the joint or contacting one another.

[0063] The pop-up structures were manually opened with precision tweezers and the deployed height of the structure was measured using calipers.

[0064] Integrated Device Testing

[0065] The integrated device was deployed from an Olympus CF-100L endoscope onto porcine stomach tissue samples using an FEP (Fluorinated Ethylene Propylene) tube to serve as an overtube to contain the integrated device, as described in FIG. 1A and FIG. IB. This added diameter is comparable to commercially available endoscopes in common use, which have outside diameters ranging from about 12.2 - 21 mm. Placing the device with thickness of 4.70 mm and width of 10 mm tangential to the outer surface of the endoscope increases the effective endoscope diameter to 20 mm, but geometric design changes could decrease this diameter to operate with a smaller overtube. Negative pressure (92 kPa) was applied through the vacuum gripper to anchor the device to the tissue before the two bellows actuators were concurrently inflated.

[0066] The structure of porcine stomach is comprised of mucosa and muscularis layers which together measure 2500 μιτι thick. This is thicker than reported thicknesses of human GI tract mucosa and muscularis layers of the intestinal wall, which vary from 495-1090 μιτι, thus making porcine stomach an acceptable substitute for benchtop ex vivo testing. Using conventional endoscopy tools, the retracted porcine stomach tissue was successfully contacted by tools inserted through the endoscope working channel.

[0067] RESULTS

[0068] Exemplary bellows actuators with internal rigid PTFE disks are shown in FIG.

3A. While the heights of the actuators can vary, in some embodiments the deflated height of the four-stage bellows without rigid internal disks is 0.85 mm with an expanded height of 18 mm; the deflated height of the comparable actuator with internal disks is 1.8 mm with a comparable expanded height.

[0069] FIG. 3A, FIG. 3B, FIG. 3C, FIG. 3D, and FIG. 3E illustrates various components that can be integrated to form an embodiment of a tissue retraction device. FIG. 3A illustrates an embodiment of a four-stage TPE bellows actuator 50 with rigid internal disks (shown in various stages of expansion) to expand the tissue retraction device. FIG. 3B illustrates an embodiment of a silicone elastomer vacuum gripper 54 that is configured to grip the tissue to be retracted. FIG. 3C illustrates an embodiment of a pop-up book MEMS structure 52 comprised of structural, flexural, and adhesive layers. These are laminated together to create the tissue retraction device 60 as shown in FIG. 3D and FIG. 3E. FIG. 3D illustrates the integrated device 60 in an undeployed state, and FIG. 3E illustrates the integrated device 60 fully expanded by inflated bellows actuators 62, 64.

[0070] Bellows Actuator Force Characterization (Extension)

[0071] In extension, four-stage bellows actuators could produce 10 N of force when expanding from fully flat. The relationship between pressure and area as F = P x A holds at low displacement heights, and can be better described as AF = ΔΡ x A, with the rate of force increasing with a marginal increase in pressure remaining constant across various displacement heights. Regardless of total height, forces on the order of Newtons were produced. Based upon the AF = ΔΡ x A relationship, given the average slope of the plot in FIG. 4, the effective area is found to be 41.7+ 8.46 mm2. This yields an experimental result for diameter of 7.29 mm, which is 8.88% less than the diameter of the rigid PTFE disk (8 mm) and 19% less than that of the bellows chamber (9 mm). FIG. 4 illustrates an example graph of pressure vs. force for four-stage bellows actuators in extension at various displacement heights.

[0072] The above slope data for calculating marginal force exerted with a change in pressure can be combined with displacement results shown in FIG. 5 to generate an expression for the observed behavior of the bellows actuator. FIG. 5 illustrates an example graph of displacement (mm) vs. pressure (kPa) during inflation of a four-stage bellows actuator with top and bottom TPE faces attached to 381 mm FR4 with 3MR 9877 sheet adhesive. To determine the force to be exerted at a particular height of an actuator with a 9 mm outer diameter and an 8 mm outer diameter embedded rigid disk, the required pressure value can be interpolated from FIG. 5, or approximated by a linear fit, with the linear change added to this fixed offset. This means that

F = (4.17 x 1(Γ ⁵ )(ΔΡ) (2) where AP = P _input — Poisp, the difference between final input pressure and the displacement pressure required for the bellows actuator to reach a particular height.

[0073] The slope here results from FIG. 4 and P _Disp is the interpolated pressure required for the bellows actuator to reach a particular height. P _D i _sp can be found with a linear model fitted to the displacement vs. pressure data, which holds with an R-square value of 0.990 at displacements greater than 6 mm. The linear model

= (4.78 x 10 ² ) (P _Disp ) + 5.41 (3) can be used in conjunction with Eqn. 2 to get an estimate of the forces these actuators can produce at large displacements, above 6 mm. Below this displacement, the simple F = P x A model described previously could be used to estimate the forces produced. The linear fit above 6 mm of displacement is sufficient for a device such as this, because we assume that the forces applied at large displacements (to sustain tissue retraction) are more important than those applied at small displacements. 2 mm of bellows actuator displacement is necessary for the base of the device to contact the tissue, due to the height of the vacuum gripper. This model is limited because the actuators deform when encountering resistance, but is presented as a useful way to estimate forces produced in a particular configuration.

[0074] Bellows Actuator Force Characterization (Retraction)

[0075] When fixtured in an extended state with top layer and bottom layer of the bellows constrained 10 mm apart, the maximum force outputted by a four-stage bellows actuator with rigid internal PTFE disks peaked at 3.096 N. The drop in force output after the peak value results from time-dependent behavior of the actuators as they continually buckle and compress inwards with sustained negative pressure. Intemal disks of 254 μιτι thickness resulted in a peak force output of 3.10 N compared to 1.68 N for an otherwise identical actuator with 76.2 μιτι internal disks, as shown in FIG. 6. FIG. 6 illustrates an example graph of pressure vs. force for four-stage bellows actuators in retraction, with and without rigid intemal disks. Top and bottom TPE faces are bonded to FR4 sheets and fixed at 10 mm displacement. This represents a 1.8-fold increase in applied force by bellows actuators in retraction, a substantial increase in force exerted compared to prior versions of these actuators with thinner TPE and PTFE layers, validating the prediction made from Eqn. 1. FIG. 7 A illustrates an embodiment of a bellows actuator with internal PTFE film undergoing buckling during retraction testing with applied vacuum. FIG. 7B illustrates one embodiment of a bellows actuator with rigid internal disks resisting buckling under applied vacuum. The buckling of actuators with 76.2 μηι internal disks is shown in FIG. 7A, and the resistance to buckling for actuators with 254 μηι internal disks is visible in FIG. 7B.

[0076] Vacuum Gripper Lifting Characterization

[0077] Vacuum grippers made from a cast silicon elastomer were successful in lifting 40 g masses of porcine stomach tissue, corresponding to exerted forces in excess of 0.40 N. This is comparable to those measured in the literature for similar grippers that produced up to 1.2 N.

[0078] Integrated Device Retracting Tissue

[0079] FIG. 8A illustrates an embodiment of an integrated device encased in 23.81 mm outer diameter overtube. FIG. 8B illustrates the integrated device during deployment and overtube retraction. FIG. 8C illustrates a view from an endoscope distal camera, showing an end-effector in the foreground. FIG. 8D illustrates the deployed device retracting tissue, the endoscope with a tool contacting tissue retracted by integrated device, as an electrocautery tool that can be used to ablate tissue.

[0080] The integrated device was placed inside an FEP overtube (23.81 mm outer diameter and 22.23 mm inner diameter) with the Olympus CF-100L endoscope (FIG. 8 A). Following the scheme described in FIG. 1, the overtube was retracted from the endoscope to expose the device, as shown in FIG. 8B. This proof of concept demonstration of deployment validates the described workflow as a means of conducting the device to the site of a lesion. The vacuum gripper is then actuated with applied negative pressure, and inflation of the soft bellows actuators begins, retracting the porcine stomach tissue, as shown in FIG. 9. FIG. 9 illustrates an embodiment of an integrated device deployed on porcine stomach tissue. As shown, the tissue is retracted to height of 13.5 mm. An end-effector is deployed through the working channel of the endoscope, which is capable of interacting with the retracted tissue with visual feedback provided by the endoscope distal illuminated camera, as shown in FIG. 8C. [0081] As shown in FIG. 8D, the tip of the endoscope is decoupled from the integrated tissue retraction device (linked only by flexible tubing for the vacuum gripper and soft bellows actuators). Once the tissue retraction device is deployed and retracting tissue, the surgeon is free to manipulate the endoscope to best approach the retracted tissue for electrocautery and biopsy.

[0082] Various geometric designs of the pop-up MEMS devices can be used. In an embodiment, the MEMS has a sharp, planar structure due to the nature of the laser micro- machined layers. In an embodiment, the MEMS can have a geometric design that includes fillets to the corners or encasing the structure in a layer of soft silicone elastomer.

[0083] In some embodiments, a device fabricated with pop-up book MEMS techniques can be used to retract tissue in the GI tract while remaining decoupled from the endoscope tip. In an embodiment, a layer-by-layer manufacturing method is provided for using heat and pressure to bond TPE sheets to create pockets with sufficient depth to contain a rigid PTFE disk within each chamber of a larger bellows actuator, using PTFE forms to deform the TPE while at elevated temperatures. The manufacturing method allows for batch fabrication, as well as the inclusion of additional bellows chambers to customize the final stroke of the actuator.

[0084] The inclusion of internal rigid planar disks expands the capabilities of soft TPE bellows actuators, increasing the potential use cases for a mostly-soft bidirectional actuator. On the millimeter-to-centimeter scale, soft TPE bellows offer a relatively large stroke and the ability to exert sustained forces. Furthermore, the bellows actuator design offers the potential to exert proportionally larger forces at the centimeter-scale with similarly large flat-to- expanded ratios, if designed and fabricated with larger bellows chambers.

[0085] The retraction device can be deployed from conventionally used endoscopes to provide the necessary counteraction to ablate tissue, paving the way for applications in endoscopic removal of early stage cancers. In an embodiment, the tissue retraction devices described herein can be utilized by surgeons and endoscopists who perform complex surgical and diagnostic procedures in the gastrointestinal tract with flexible endoscopes. The integrated tissue retraction device offers surgeons an additional method to simplify endoscopic procedures, potentially solving the issues of limited distal tip dexterity and the extensive training requirements to perform these procedures. The device can be adapted to retract larger portions of tissues using a row or array of vacuum grippers to excise larger lesions, as well as inflatable bellows actuators described here for other procedures where an initially-flat device capable of substantial expansion and exertion of force as a distance is beneficial, such as collapsed lungs or airways, as well as further applications in the GI tract. The device can thus find applications in all endoscopic procedure where it is necessary to distally manipulate endoluminal tissues, for example, including but not limited to removal of early stage cancer to polyps.

[0086] In order to fit within the current work-flow of therapeutic endoscopic procedures, an embodiment of a tissue retraction device can be introduced into the body along the outside of the distal end of an endoscope and encased in a retractable overtube. By automating the act of placing tissue under tension and decoupling this action from the motion of the endoscope tip, the integrated devices herein have the potential to expand surgeons' capabilities and increase the number of surgeons capable of performing these types of procedures.

[0087] A method of performing tissue retraction is also provided, comprising deploying a tissue retraction device from an outer surface of an elongate body of an endoscopic device such that the tissue retraction device is positioned adjacent to a target tissue to be retraction and manipulated by the endoscopic device, and anchoring the tissue retraction mechanism to the target tissue using a tissue retraction mechanism. At least one actuator coupled to the tissue retraction mechanism is deployed from an unexpanded state during which the tissue retraction mechanism anchors the target tissue into an expanded state such that the tissue retraction mechanism applies a force to the target tissue to cause retraction of the target tissue.

[0088] While various embodiments have been described for purposes of this disclosure, such embodiments should not be deemed to limit the teaching of this disclosure to those embodiments. Various changes and modifications may be made to the elements and operations described above to obtain a result that remains within the scope of the systems and processes described in this disclosure. All patents, patent applications, and published references cited herein are hereby incorporated by reference in their entirety. It should be emphasized that the above-described embodiments of the present disclosure are merely possible examples of implementations, merely set forth for a clear understanding of the principles of the disclosure. Many variations and modifications may be made to the above- described embodiment(s) without departing substantially from the spirit and principles of the disclosure. It will be appreciated that several of the above-disclosed and other features and functions, or alternatives thereof, may be desirably combined into many other different systems or applications. All such modifications and variations are intended to be included herein within the scope of this disclosure, as fall within the scope of the appended claims.

[0089] The described embodiments are to be considered in all respects only as illustrative and not restrictive and the scope of the presently disclosed embodiments is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope. Skilled artisans may implement the described functionality in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the disclosed devices and/or methods.