Catheter maneuvering device and uses thereof

Abstract

Devices and accompanying methods and systems for performing a stabilized endoluminal procedure are disclosed. A device includes a catheter defining a working channel and configured to carry multiple fluidic lines. The device includes a stabilization mechanism configured to expand in a deployed state to stabilize the catheter against tissue. A soft manipulator disposed at a distal end of the device includes multiple actuators configured to expand, to collapse, or to bend. The multiple actuators define a guided channel in communication with the working channel. A hub at a proximal end of the catheter is in coupled configuration with a stabilization actuator mechanically coupled to the stabilization mechanism. The hub defines a port in communication with the working channel and enables the passage of the fluidic lines. The device enables interventional therapies in motile environments, for example a beating-heart procedure.

Description

6200.2002002 (BU-2023-001) Catheter Maneuvering Device and Uses Thereof RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Application No.63 / 612,831, filed on December 20, 2023. The entire teachings of the above application are incorporated herein by reference. GOVERNMENT SUPPORT

[0002] This invention was made with government support under Contract Nos. EB028363 and EB035574 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND

[0003] Surgical robots for performing minimally invasive procedures may be helpful in enabling otherwise difficult or unfeasible surgical procedures and in enhancing an operator’s capabilities. The benefits of surgical robotic platforms span a variety of applications, including cardiovascular interventions and orthopedic surgeries, among others. However, the utility of current surgical robotics platforms may be limited for performing procedures in certain anatomical locations or environments due to, for example, limited dexterity and high aspect ratios. These limitations may complicate navigating a tool to an anatomical target and providing sufficient stability, dexterity, and force output to perform interventional therapies.

[0004] As a specific example, surgical robotics for beating heart procedures may need to accommodate the size discrepancy between the vasculature and the heart chambers, moving workspace generated by cardiac muscle contractions, and distant percutaneous access site. The heart may provide a large workspace and require stable force application at large bending angles. Current devices may struggle to reconcile a small size requirement for percutaneous access with preservation of distal dexterity, stability, and force transmission. SUMMARY

[0005] Devices, systems, and associated methods for endoluminal procedures are disclosed. Advantageously, such devices can dexterously maneuver within motile environments and guide existing instruments toward a variety of anatomical targets while maintaining stability and distal force transmission. - 1 - 4088749.v26200.2002002 (BU-2023-001)

[0006] A device for performing a stabilized cardiovascular procedure includes a catheter, a stabilization mechanism couple to the catheter, and a soft manipulator. The catheter includes a proximal end and a distal end and defines a working channel configured to carry multiple fluidic lines. The stabilization mechanism is configured to change between an undeployed state and a deployed state. The stabilization mechanism is configured to expand radially in the deployed state to stabilize the catheter in a lumen of a biological body (e.g., in a blood vessel). The soft manipulator is disposed distal to the stabilization mechanism and includes multiple actuators that define respective inflatable chambers fluidically coupled to the corresponding multiple fluidic lines. The multiple actuators are configured to inflate and to deflate, and the soft manipulator is configured to expand, to collapse, or to bend based on inflating and deflating of the multiple actuators. The soft manipulator is further configured to define a guided working channel in communication with the working channel of the catheter. The device includes a hub disposed at the proximal end of the catheter. The hub is in coupled arrangement with a stabilization actuator configured to deploy the stabilization mechanism to stabilize the catheter in the lumen. The hub is configured for passage of the multiple fluidic lines to couple fluidically to a fluidic actuator system. The hub defines a port continuous with the working channel, and the port is configured to enable passage of an interventional device through the catheter to perform the endoluminal procedure.

[0007] The stabilization mechanism can include a fixed end coupled statically to the catheter, a moveable end configured to move relative to the fixed end, and multiple beams extending between the fixed end and the moveable end. The moveable end can be configured to slide towards the fixed end in the deployed state causing the multiple beams to bend at least in a radial direction away from the catheter.

[0008] The stabilization mechanism can be mechanically coupled to the stabilization actuator using at least one cable. The catheter can be configured to carry the at least one cable. The stabilization actuator can be configured to deploy the stabilization mechanism by applying a tension to the cable.

[0009] The stabilization mechanism can include a rigid backbone having a length at least as long as a length of the stabilization mechanism in the undeployed state.

[0010] The stabilization mechanism can include a first stabilization element and at least one second stabilization element. For example, the first stabilization element and the at least one second stabilization element can be configured to deploy individually or to deploy collectively. - 2 - 4088749.v26200.2002002 (BU-2023-001)

[0011] A beam of the multiple beams of the stabilization mechanism can include a single panel or a plurality of panels.

[0012] The multiple beams of the stabilization mechanism can be constructed using nitinol or another alloy or polymer.

[0013] The device can include a tool guide disposed at a face of the soft manipulator, the tool guide configured to guide delivery of the interventional device by promoting orthogonality of the interventional device passing through the guided working channel with respect to the face of the soft manipulator. For example, the tool guide can increase a stiffness of the face of the soft manipulator.

[0014] In the device, an actuator of the multiple balloon actuators can be a balloon actuator. For example, each balloon actuator may be a stacked balloon actuator and can define a continuous series of inflatable chambers, a chamber of the continuous series of inflatable chambers having a concave or a bean cross-sectional shape.

[0015] The guided working channel of the soft manipulator can be of size 1 French or greater and preferably of size 7.5 French or greater. The soft manipulator can be configured to bend more than 90 degrees and preferably more than 180 degrees with respect to a base of the soft manipulator while maintaining the size of the guided working channel.

[0016] The soft manipulator can include a collapsible tubing in coupled arrangement with the multiple actuators and configured to define the guided working channel.

[0017] The device can include the fluidic lines. For example, the device can include three fluidic lines fluidically coupled to three respective inflatable chambers of three corresponding actuators.

[0018] The device can include a sensor or a marker. The sensor can be configured to detect a property of the device or an environment therein. The marker can be configured to enable the sensing of an attribute of the device.

[0019] For example, the device can include a sensor, the sensor being a force sensor disposed at a tip of the soft manipulator, the force sensor configured to detect forces applied to the tip of the soft manipulator. The device can include one or more conductive traces disposed on the outer surface of or embedded in the multiple actuators. The conductive trace(s) can be configured to couple communicatively the force sensor to a processor.

[0020] For example, the device can include a marker, the marker being a magnetic marker disposed on the soft manipulator and configured to enable sensing of a position of the soft manipulator. - 3 - 4088749.v26200.2002002 (BU-2023-001)

[0021] The device can include the interventional device. The interventional device can include, for example, an annuloplasty device or a conductive lead.

[0022] The stabilization mechanism in the undeployed state and the soft manipulator in a collapsed state can be configured to pass through an introducer sheath of diameter 1 centimeter or smaller. The stabilization mechanism can be configured to undergo at least a two-fold expansion in a fully deployed state. For example, the stabilization mechanism can be configured to expand to a diameter of 2 centimeters or greater. In general, the stabilization mechanism can be configured to expand up to a diameter that conforms with a size of a vascular lumen.

[0023] The endoluminal procedure can be a beating heart procedure, as further described herein.

[0024] The hub can define a flush port. For example, the flush port can be in communication with the working channel and configured to enable delivery of a lubricant, for example, a saline fluid, to lubricate the working channel.

[0025] A system for performing a stabilized endoluminal procedure includes the device as described above, including the catheter, the stabilization mechanism, the soft manipulator, and the hub. The system further includes an actuation system including multiple fluidic devices. The multiple fluidic devices are coupled fluidically with the respective multiple fluidic lines and are configured to inflate or deflate the multiple respective inflatable chambers of the soft manipulator by injecting or extracting a fluid.

[0026] In the system, a fluidic device of the multiple fluidic devices can be or can include a syringe. In an example, all fluidic devices are syringes.

[0027] The system can include a processor. The processor can be communicatively coupled with multiple stepper motors. The multiple stepper motors can be in coupled arrangement with the respective multiple fluidic devices of the actuation system. The multiple stepper motors can be configured to control injecting or extracting of the fluid by the respective multiple fluidic devices. The processor can be communicatively coupled with a controller, which can be configured to receive inputs from an operator. The processor can be configured to operate the multiple stepper motors based on the inputs received from the operator on the controller.

[0028] The system can include a sensor disposed on the device. The processor can be communicatively coupled to the sensor and to sense a property of the device or an environment therein using the sensor.

[0029] The system can include a magnetic marker disposed on the soft manipulator and can further include a magnetic sensor. The magnetic sensor can be configured to sense a position of - 4 - 4088749.v26200.2002002 (BU-2023-001) the magnetic marker. The processor can be communicatively coupled with the magnetic sensor and configured to detect a position of the magnetic marker on the soft manipulator.

[0030] A method for performing a stabilized endoluminal procedure includes navigating a catheter through a lumen of a biological body (e.g., a blood vessel) and stabilizing the catheter in the lumen by changing a stabilization mechanism coupled to the catheter into a deployed state. The stabilization mechanism can be configured to expand in at least a radial direction in a deployed state. The method includes actuating a soft manipulator disposed distal to the stabilizing mechanism by selectively inflating or deflating multiple actuators of the soft manipulator. The actuating includes extending, collapsing, or bending the soft manipulator, the soft manipulator configured to guide an interventional device to an anatomical location to perform the endoluminal procedure.

[0031] The method can include sensing a property of the soft manipulator, the stabilization mechanism, the catheter, or a combination thereof.

[0032] The method can include detecting a position of the soft manipulator.

[0033] The method can include changing the stabilization mechanism into an undeployed state from the deployed state to enable the removal of the catheter from the lumen.

[0034] The endoluminal procedure can be a cardiovascular procedure and stabilizing in a body lumen can include stabilizing in a blood vessel.

[0035] Embodiments of devices, systems, and methods as described herein may provide several advantages. For example, the devices, systems, and methods may include introduction of controllable bracing and stabilization using a stabilization mechanism at the entrance of a motile anatomical location, for example, a beating heart. Active guidance of interventional tools using a soft manipulator as described herein inside a beating heart may provide more precise anatomical localization and force transmission. The present approach improves over prior stabilization mechanisms inside vessels, which showed limited success previously due to challenges in manufacturing and risks associated to blocking or disrupting blood flow.

[0036] The devices, systems, and methods as described are expected to substantially improve current workflow for endoluminal procedures, for example, beating heart procedures, and lead to a new surgical procedure in interventional cardiology. Generally, interventional cardiologists focus on diagnostic procedures and small repairs using catheters. More serious procedures, like valve repair and reconstruction, often require cardiopulmonary bypasses, making them significantly riskier for a patient. The devices, systems, and methods as described can make - 5 - 4088749.v26200.2002002 (BU-2023-001) valve repair accessible to interventional cardiologists, thereby also making it much more accessible and safer for the general population. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee.

[0038] The foregoing will be apparent from the following more particular description of example embodiments, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments.

[0039] FIG.1 illustrates an example embodiment of a system for performing a stabilized endoluminal procedure. The system can operate in a six-step workflow including: (i) a user inputting controls into the system’s controller, (ii) the inputs are interpreted by control hardware, which may include a processor or microcontroller, (iii), the control hardware sends signals to an actuation system, which may actuate fluidic devices, (iv) the user deploys a stabilization mechanism using a stabilization actuator, e.g., a syringe actuation system with cable actuators, (v) the stabilization mechanism deploys against a blood vessel, e.g., a superior vena cava, and (vi) a soft manipulator (e.g., a soft robot) is controlled as a result of steps (i) to (iii).

[0040] FIG.2 illustrates an example embodiment of a device for performing a stabilized endoluminal procedure in a radially collapsed state enabling passage through vasculature.

[0041] FIG.3A illustrates an example embodiment of a device for performing a stabilized endoluminal procedure with a port for endoluminal devices and a flush port, along with an inset of FIG.3A showing a detailed view of the port for the interventional device.

[0042] FIG.3B illustrates the device of FIG.3A inserted through a blood vessel using an introducer sheath.

[0043] FIG.4 illustrates an example approach for performing an endoluminal beating-heart procedure with an inset showing a magnified view of a heart.

[0044] FIG.5A illustrates an example procedure in a beating heart using a conventional endoluminal device.

[0045] FIG.5B illustrates an example procedure in a beating heart using a system for performing a stabilized endoluminal procedure.

[0046] FIG.5C illustrates another example procedure in a beating heart using a system for performing a stabilized endoluminal procedure. - 6 - 4088749.v26200.2002002 (BU-2023-001)

[0047] FIG.6A illustrates an example embodiment of a device navigating through a body lumen (e.g., blood vessel) to the right atrium of a heart, in which the system includes multiple undeployed stabilization mechanisms.

[0048] FIG.6B illustrates the system of FIG.6A with the stabilization mechanism deployed and a soft manipulator in a deployed state.

[0049] FIG.6C illustrates the system of FIG.6B performing a therapeutic procedure.

[0050] FIG.7A illustrates an example embodiment of a stabilization mechanism including a rigid backbone.

[0051] FIG.7B illustrates another example embodiment of a stabilization mechanism including two stabilization elements.

[0052] FIG.8 illustrates an example embodiment of a device for performing a stabilized cardiovascular procedure navigating through a body lumen to the right atrium of a heart, in which the system includes multiple deployed stabilization mechanisms.

[0053] FIG.9A illustrates an example experiment to evaluate the effect of a stabilization mechanism on a flow of liquid through a lumen.

[0054] FIG.9B illustrates flow measurements from the experiment of FIG.9A.

[0055] FIG.10A illustrates an example experiment and results thereof for measuring reaction forces on a deployed stabilization mechanism from an axial direction.

[0056] FIG.10B illustrates an example experiment and results thereof measuring reaction forces on a deployed stabilization mechanism from a radial direction.

[0057] FIG.11A illustrates an example experiment and results thereof measuring forces generated on a sensor by a stabilization mechanism versus tension in a stabilization actuator mechanically coupled to the stabilization mechanism.

[0058] FIG.11B illustrates an example model of stress concentration areas for maximum experimental force generated by a stabilization mechanism.

[0059] FIG.12 illustrates an example embodiment of a rigid backbone of a stabilization mechanism, with an inset showing a magnified view of the rigid backbone.

[0060] FIG.13A illustrates an example fabrication process for a stabilization mechanism including multiple sheets of material.

[0061] FIG.13B illustrates an additional example fabrication process for a stabilization mechanism including a single sheet of material.

[0062] FIG.14A illustrates an example embodiment of a soft manipulator in a collapsed state. - 7 - 4088749.v26200.2002002 (BU-2023-001)

[0063] FIG.14B illustrates the soft manipulator of FIG.14A in a bent actuation state.

[0064] FIG.14C illustrates the soft manipulator of FIG.14A in an extended actuation state.

[0065] FIG.15A illustrates an example embodiment of a soft manipulator with a bean- shaped stacked balloon actuator in a bent actuation state.

[0066] FIG.15B illustrates an example embodiment of a soft manipulator with a circular stacked balloon actuator in a bent actuation state.

[0067] FIG.16 illustrates an example diagram of a soft manipulator similar to the soft manipulator of FIG.15A in a cross-sectional view.

[0068] FIG.17A illustrates an example experiment for measuring force transmission by a soft manipulator of a stabilized device.

[0069] FIG.17B illustrates measurements of force transmission over time for the soft manipulator of FIG.17A at two extended actuation states.

[0070] FIG.17C illustrates measurements of force transmission over time for the soft manipulator of FIG.17A at two bent actuation states.

[0071] FIG.18A illustrates a bend angle of an example embodiment of a soft manipulator actuated using one inflatable chamber.

[0072] FIG.18B illustrates a bend angle of an example embodiment of a soft manipulator actuated using two inflatable chambers.

[0073] FIG.19 illustrates an example experiment and results thereof for evaluating a combined stiffness of a soft manipulator and an endoluminal device deployed through the soft manipulator.

[0074] FIG.20A illustrates a deployment angle of an example embodiment of an endoluminal device using an example soft manipulator with a tool guide.

[0075] FIG.20B illustrates a deployment angle of an example embodiment of an endoluminal device using an example soft manipulator without a tool guide.

[0076] FIG.21A illustrates an example computer-simulated model of a soft manipulator in the right atrium of a heart.

[0077] FIGS.21B and 21C illustrate task spaces of the soft manipulator in the computer- simulated model of FIG.21A in the right atrium of the heart.

[0078] FIG.22 illustrates an example experiment for navigating a device for performing a stabilized endoluminal procedure to several predetermined locations. - 8 - 4088749.v26200.2002002 (BU-2023-001)

[0079] FIG.23 illustrates an example embodiment of a system for performing a stabilized endoluminal procedure navigating a bend in a model of a body lumen, with an inset showing a top-down view of the device navigating the bend.

[0080] FIG.24A illustrates an example embodiment of a soft manipulator with a collapsible tubing configured to define a guided working channel.

[0081] FIG.24B illustrates the collapsible tubing of FIG.24A in collapsed and extended states.

[0082] FIG.24C illustrates an example model of kinematics of a segment of the collapsible tubing of FIGS.24A and 24B.

[0083] FIG.25 illustrates an example fabrication process for the collapsible tubing of FIGS. 24A and 24B.

[0084] FIG.26 illustrates an example embodiment of a soft manipulator with a force sensor, a ring magnet, and conductive traces.

[0085] FIG.27 illustrates an example embodiment of a soft manipulator with conductive traces.

[0086] FIG.28A illustrates an example embodiment of a sensor encapsulated in silicone and associated with a stabilization mechanism.

[0087] FIG.28B illustrates an example stabilization mechanism with conductive traces.

[0088] FIG.29A illustrates an example embodiment of a soft manipulator with a magnet positioned within a chamber of a heart and a magnetometer positioned external to a human body configured to measure a position of the disk magnet.

[0089] FIG.29B illustrates example experimental results evaluating errors between localization of a soft manipulator at different actuation states using an electromagnetic tracker versus using the disk magnet and the magnetometer of FIG.29A.

[0090] FIG.30 illustrates a controller, control hardware, and an actuation system for an example system for performing a stabilized endoluminal procedure, with an inset showing a magnified view of actuation components for a fluidic device.

[0091] FIG.31 illustrates an example application of a system for performing a stabilized endoluminal procedure, wherein (i) actuation components of the system are placed on a table near a patient, enabling an operator to control (ii) a device of the system inserted into the patient through an incision site.

[0092] FIG.32 illustrates an example experiment for performing a tricuspid valve annular puncture task using a system for performing a stabilized endoluminal procedure. - 9 - 4088749.v26200.2002002 (BU-2023-001)

[0093] FIGS.33A-D illustrate example experiments using a device for performing a stabilized endoluminal procedure with a soft manipulator in collapsed states (FIGS.33A, 33C) and after successful puncture (FIGS.33B, 33D) for the experimental setup, schematically illustrated in a horizontal configuration, of FIG.32.

[0094] FIG.34 illustrates example findings of time to complete successful puncture using the experimental setup of FIG.32 in static and beating tricuspid valve annular tissue.

[0095] FIGS.35A-D illustrates an example soft manipulator in vertical (FIGS.35A, 35B) and angled deployment (FIGS.35C, 35D) configurations bending due to beating motions.

[0096] FIG.36 illustrates example measurements of contact force transmission over time in a beating environment using the experimental setup of FIG.32.

[0097] FIGS.37A-C illustrate an example coronary sinus lead placement procedure using a device for performing a stabilized endoluminal procedure.

[0098] FIG.38A illustrates an example experiment for a coronary sinus lead placement procedure in an explanted porcine heart.

[0099] FIG.38B illustrates example results of procedure times for performing a coronary sinus lead placement procedure as shown in FIGS.37A-C.

[0100] FIG.38C illustrates example results of an experiment measuring intraluminal pressures in a hybrid biorobotic beating heart with and without a device for performing stabilized endoluminal procedures.

[0101] FIGS.39A-C illustrate an example in vivo coronary sinus lead placement procedure viewed under x-ray fluoroscopy.

[0102] FIG.40 illustrates example measurements of heart rate before and after application of a pacing lead while performing the procedure of FIGS.37A-C.

[0103] FIG.41 illustrates an example embodiment of a device for performing stabilized endoluminal procedures with modifications for performing annuloplasty procedures.

[0104] FIGS.42A-F illustrate example metrics for an experiment comparing coronary artery lead placement using a device for performing a stabilized endoluminal procedure and a conventional catheter. DETAILED DESCRIPTION

[0105] A description of example embodiments follows.

[0106] Minimally invasive surgical procedures, which may include the use of transcatheter systems and devices, may offer a number of advantages over conventional surgery, including a reduction in operation times, perioperative complications, recovery periods, and costs. However, - 10 - 4088749.v26200.2002002 (BU-2023-001) current robotic systems for minimally invasive procedures may be limited by a number of factors, such as low dexterity, high aspect ratios, and limited force transmission. Environment- specific conditions may impose additional challenges towards successful minimally invasive therapies.

[0107] As a specific example, the beating-heart may present a number of unique challenges specific to the intracardiac environment that hinder the use of percutaneous beating-heart approaches. These may include (i) a size discrepancy between the vasculature and heart chambers, (ii) a moving workspace generated by cardiac muscle contraction, and (iii) remote tool operation via a distant percutaneous access site. The discrepancy in scale between the vasculature and heart chambers forces the interventional tools used in the heart to remain small. Interventional catheters must traverse up to a meter or more through peripheral blood vessels, which can accommodate devices up to 8 mm in diameter (i.e., 24 Fr) However, the right atrium (RA), the smallest of the four chambers, has an apicobasal diameter ranging from 34.9 to 58.6 mm. Limiting the size of the tools to the vascular scale often comes at the detriment of distal force transmission or dexterity once inside the larger intracardiac workspace. In addition, the motile workspace poses a challenge in procedures such as cardiac mapping or radiofrequency ablation, in which interventional tools must maintain stable millinewton-level forces. Conversely, procedures such as valve repair require newton-level distal forces despite remote operation making force transmission over the length of the device difficult. The beating heart is one of the few anatomical workspaces that present clinicians with a combination of all three listed challenges, making minimally invasive intracardiac intervention especially difficult.

[0108] To address these challenges, robot-assisted technologies have been established, especially in the field of electrophysiology (EP) where low contact forces between the catheter and the tissue are required. For example, the Sensei and Magellan (Auris Health Inc.), the Amigo (Catheter Precision Inc.), and the Niobe (Stereotaxis Inc.) are commercially available robotic guide catheters for radiofrequency ablation and cardiac mapping. These robotic platforms make use of cable-driven and magnetically actuated catheter sheaths with three degrees of freedom (DoFs), increasing the interventional tool’s achievable task space while remaining small enough to conform with the vascular scale. However, these robots do not account for intracardiac motion. While magnetic actuation results in improved distal force generation, it requires complex and expensive actuation systems to generate external magnetic fields. Cable-driven actuation reduces the need for expensive equipment, but cable friction prompts losses in distal force transmission. Reduced force output is suitable for use in the field of EP, but it is unsuitable - 11 - 4088749.v26200.2002002 (BU-2023-001) for structural heart repairs and other tissue manipulation tasks. Combining the maneuverability of these EP robots with greater stability and force transmission would improve the chances of procedural success in structural repair, yet there are currently no commercial robots designed for this.

[0109] Research prototypes have been developed to further address the aforementioned challenges. Several groups have addressed the vascular size constraint with small and dexterous catheters that can navigate tortuous paths and perform interventional procedures. While the actuation methods vary across these devices, they maintain an overall flexibility that allows for easy vascular navigation. Another set of devices addresses the motile environment with a variety of methods. One group designed a robot to operate on the outer surface of the heart. The robot uses mechanical bracing against the local anatomy to mitigate the effects of cardiac motion and was able to perform myocardial injections. Cardiac motion has also been addressed by shape- locking against blood vessels and anchoring through or onto intracardiac surfaces. Such systems have been shown to improve stability while guiding catheters through the vasculature or atrial septum. Alternatively, tool stability inside the beating heart has been addressed via motion compensation algorithms. For example, force feedback combined with motion compensation via three-dimensional (3D) ultrasound has allowed users to compensate for rhythmic heart motions and maintain tissue contact forces. Last, the challenge with force transmission during remote operation has been addressed by focusing on distal stiffness using concentric tubes or rigid structural backbones to generate forces compatible with the requirements for reconstructive procedures such as valve repair.

[0110] Despite these advances, current devices struggle to reconcile a small size requirement for percutaneous access with preservation of distal dexterity, stability, and force transmission. This encumbers standard procedures in EP and interventional cardiology and may preclude the advancement of minimally invasive approaches to complex reconstructive procedures such as valve repair. There is a need for devices that can dexterously maneuver within the heart and guide existing instruments toward a variety of anatomical targets while maintaining stability and distal force transmission.

[0111] The delicate nature of biological soft tissue has motivated further research into soft and compliant robots. Soft surgical robots aim to provide the same benefits as their rigid counterparts while increasing safety and accessibility and reducing costs. Key features include minimization of stress concentrations by conforming to delicate structures and the ability to fit into apertures smaller than their nominal size. Exploiting these benefits, soft robots have been successfully - 12 - 4088749.v26200.2002002 (BU-2023-001) introduced for endovascular navigation, cardiac operation, neurosurgery, lung surgery, and endoscopy.

[0112] Developing a soft robotic platform that provides enough dexterity to reach a range of anatomical targets, enough stability to maintain constant contact on motile targets, and enough mechanical leverage to generate newton-level forces may enable catheter-based interventions and minimally invasive therapies for complex or motile anatomical environments.

[0113] As used herein, an endoluminal procedure includes cardiac procedures, endovascular procedures, endoscopic procedures, or other types of procedures in a body lumen, i.e., a lumen in a human or animal body. Although specific embodiments of devices, systems, and methods are described herein with respect to cardiovascular procedures, it should be understood that the embodiments of the invention can be used in other endoluminal procedures.

[0114] A soft robotic platform is described herein for minimally invasive endoluminal procedures, for example, intracardiac beating-heart procedures and interventions. The soft robotic platform may comprise a deployable stabilization mechanism and a collapsible soft manipulator. The combination of stabilization and robotic tool guidance enables versatility in performing clinical procedures such as coronary sinus lead placement and less standardized procedures such as tricuspid valve repair. The platform is further capable of guiding existing interventional instruments toward a variety of anatomical locations or anatomical targets, e.g., the right atrium of a heart, via a working channel that runs through an entire length of the robotic platform. In this way, it provides a direct connection between a user and the anatomical location in the heart.

[0115] In some embodiments, the soft robotic platform features a shape-locking, expandable stabilization mechanism manufactured with a 2D paradigm used in fabrication of millimeter- scale mechanisms. The stabilization mechanism is capable of shape-locking against a vessel of the human body, e.g., a proximal superior vena cava (SVC), without puncturing it, preventing undue harm to the delicate SVC vasculature and the sinoatrial node. In addition, stabilization at a location local to the heart shifts a fulcrum of a catheter of the soft robotic platform from a peripheral access point closer to the anatomical target. Moving the fulcrum toward the target site provides more mechanical leverage to the surgical tool, improving distal force transmission compared to non-stabilized instrumentation (see, e.g., FIGS.5A-C). The improved force transmission and stability at a distal end of the robot is independent of how far entry access for the catheter is from the anatomical target. However, moving the fulcrum towards the tip of a - 13 - 4088749.v26200.2002002 (BU-2023-001) catheter decreases mobility of the tip. Without an addition of an active steering component, distal stabilization would notably reduce the catheter’s reachable intracardiac task space.

[0116] A multi DoF soft robot is included to expand the soft robotic platform’s task space. The soft robot was designed to collapse to a diameter of 24 Fr, allowing it to fit in peripheral blood vessels, and then expand once inside the anatomical target, e.g., the heart, to increase surface area and force output of the soft robot. The soft robot further addresses challenges of instability in a motile environment through inherent material damping. It is capable of conforming to the heart wall’s motions, thereby maintaining contact with a moving target during simulated procedures.

[0117] Example devices, systems, and methods including a soft robot for cardiac interventions have been described in the article by Jacob Rogatinsky et al. “A multifunctional soft robot for cardiac interventions.” Sci. Adv.9, eadi5559 (2023), DOI:10.1126 / sciadv.adi5559, pp.1-16, published 25 October 2023. The article includes Supplemental Materials available online at: www.science.org / doi / suppl / 10.1126 / sciadv.adi5559 / suppl_file / sciadv.adi5559_sm.pdf. The entire teachings of the article and Supplemental Materials are incorporated herein by reference.

[0118] FIG.1 illustrates an example embodiment of a system for performing a stabilized endoluminal procedure, which includes six components: (i) a user inputting controls into the system’s controller, (ii) the inputs are interpreted by a control hardware, which may include a processor or microcontroller, (iii), the control hardware sends signals to an actuation system, which may actuate fluidic devices, (iv) the user deploys a stabilization mechanism using a stabilization actuator, e.g., a syringe actuation system with cable actuators, (v) the stabilization mechanism deploys against a blood vessel, e.g., a superior vena cava, and (vi) a soft manipulator (e.g., a soft robot) is controlled as a result of steps (i) to (iii).

[0119] The system 100 comprises a device 102 for performing a stabilized endoluminal procedure, an actuation system 128, control hardware 130, and a controller 132. The control hardware 130 may include a processor, for example, the processor 3031 as shown in FIG.30. The device 102 includes a catheter 104, e.g., a flexible catheter, which includes a proximal end 106 and a distal end 108, and the catheter 104 defines a working channel 110 and is configured to carry multiple fluidic lines 112. The device 102 further comprises a stabilization mechanism 114 coupled to the catheter 104. The stabilization mechanism 114 is configured to change from an undeployed state and a deployed state, wherein the stabilization mechanism is configured to expand, for example, expand radially, in the deployed state to stabilize the catheter 104 in a body - 14 - 4088749.v26200.2002002 (BU-2023-001) lumen, as illustrated in FIG.2. The device 102 further comprises a soft manipulator 116, disposed distal to the stabilization mechanism 114, that includes multiple actuators 118. The multiple actuators 118 may be multiple balloon actuators that define respective inflatable chambers 120 fluidically coupled to the corresponding multiple fluidic lines 112. The multiple actuators 118 are configured to inflate and to deflate, and the soft manipulator 116 is configured to expand, to collapse, or to bend based on inflating and deflating of the multiple actuators 118. The soft manipulator is further configured to define a guided working channel 122 in communication with the working channel 110. The device 102 further comprises a hub 124 disposed at the proximal end of the catheter 104. The hub 124 is in coupled arrangement with a stabilization actuator 126, e.g., a modified syringe, configured to deploy the stabilization mechanism 114 to stabilize the catheter 104 in a body lumen. The hub 124 is further configured for passage of the multiple fluidic lines 112 to the actuation system 128, for example, a fluidic actuation system. The hub can also define a port, as shown in FIG.2 (port 242), continuous with the working channel 110, wherein the port is configured to enable passage of an interventional device through the catheter 104 to perform an endoluminal, for example, a cardiovascular, procedure. The stabilization mechanism 114 may include a rigid backbone 115 having a length at least as long as a length of the stabilization mechanism in the undeployed state.

[0120] FIG.2 illustrates an example embodiment of a device 202 for performing a stabilized endoluminal procedure in a radially collapsed state enabling passage through vasculature. The device 202 comprises a catheter 204 with a proximal end 206 and a distal end 208. The device further comprises a stabilization mechanism 214 coupled to the catheter. The stabilization mechanism may be in an undeployed state 214-1 or a deployed state 214-2, the deployed state 214-2 of the stabilizing the catheter 204 in a body lumen, for example, a model body lumen 234. The device further comprises a soft manipulator 216 disposed distal to the stabilization mechanism. The soft manipulator 216 may be deployed in a collapsed state 216a or in an actuated state 216b. The soft manipulator 216 includes a tool guide 236 to provide guidance for an endoluminal or an interventional device, e.g., a guidewire 238. The device 202 further comprises a hub 224 disposed at the proximal end of the catheter 204. The hub is in coupled arrangement with a stabilization actuator 226 configured to deploy the stabilization mechanism 214. The stabilization actuator 226 may be in an undeployed state 226a or a deployed state 226b, corresponding to the undeployed state of the stabilization mechanism 214a and the deployed state of the stabilization mechanism 214b. The stabilization actuator 226 is affixed into the undeployed state 226a or the deployed state 226b by a cable lock 240. The hub defines a port - 15 - 4088749.v26200.2002002 (BU-2023-001) 242 continuous with a working channel (not shown but similar with respect to working channel 110 of FIG.1), wherein the port is configured to enable passage of an interventional device through the catheter 204.

[0121] FIG.2 further illustrates the stabilization actuator 226 as a modified syringe. The stabilization actuator may be mechanically coupled to the stabilization mechanism 214 using at least one cable, for example, a Bowden cable. The termination of the Bowden cable for the stabilization mechanism 214 routes through the cable lock 240, for example, a Luer lock valve, and into the stabilization actuator 226. The stabilization actuator 226 may apply a tension to the cable by pushing or pulling a plunger of a syringe, the syringe providing haptic feedback for a user, and the stabilization mechanism 214 may be locked into a configuration by the cable lock 240.

[0122] FIG.3A illustrates an example embodiment of a device 302 for performing a stabilized endoluminal procedure with a port for endoluminal devices and a flush port, an inset of FIG.3A showing a detailed view of the port for the interventional device. The device 302 may be similar to the device 102, 202 and includes a catheter 304, which includes a proximal end 306 and a distal end 308. In FIG.3A, the catheter 304 is shown having a shortened length for illustrative purposes. In general, the length of the catheter 304 may be adapted for a particular application. The catheter 304 defines a working channel (not shown but similar with respect to the working channel 110 of FIG.1) and is configured to carry multiple fluidic lines 312. The device 302 further comprises a stabilization mechanism 314 coupled to the catheter 304. The stabilization mechanism 314 is configured to change from an undeployed state and a deployed state, wherein the stabilization mechanism is configured to expand radially in the deployed state to stabilize the catheter 304 in a body lumen, for example, as illustrated in FIG.2. Continuing with respect to FIG.3, the device 302 further comprises a soft manipulator 316, disposed distal to the stabilization mechanism 314, that includes multiple actuators 318. The multiple actuators 318 define respective inflatable chambers (not visible but similar with respect to inflatable chambers 120) fluidically coupled to the corresponding multiple fluidic lines 312. The multiple actuators 318 are configured to inflate and to deflate, and the soft manipulator 316 is configured to expand, to collapse, or to bend based on inflating and deflating of the multiple actuators 318. The soft manipulator is further configured to define a guided working channel (not visible but similar with respect to inflatable chambers 122) in communication with the working channel. The device 302 further comprises a hub 324 disposed at the proximal end of the catheter 304. The hub 324 is in coupled arrangement with a stabilization actuator 326 configured to deploy the - 16 - 4088749.v26200.2002002 (BU-2023-001) stabilization mechanism 314 to stabilize the catheter 304 in a body lumen. The hub 324 is further configured for passage of the multiple fluidic lines 312 to an actuation system, for example, the fluidic actuation system 128 of FIG.1. The hub also defines a port 342, continuous with the working channel 310, wherein the port 342 is configured to enable passage of an endoluminal device 338 through the catheter 304 to perform an endoluminal procedure. The hub 324 may further include a flush port 344. The flush port 344 may be in communication with the working channel and configured to enable delivery of a lubricant, for example, a saline fluid, to lubricate the working channel.

[0123] The device 102, 202, 302 may be assembled by connecting the soft manipulator 116, 216, 316 to a multi-lumen tube, for example, the rigid backbone 115, of the stabilization mechanism 114, 214, 314. A single layer of material, for example stainless steel, may be used to more robustly couple a base of the soft manipulator 116, 216, 316 and the multi-lumen tube. The steel base may be adhered to the soft manipulator 116, 216, 316 and the stabilization mechanism 114, 214, 314 using a bioadhesive. The multiple fluidic lines 112, 312 may be routed through channels in the multi-lumen tube of the stabilization mechanism 114, 214, 314, allowing them to remain hidden underneath the material of the stabilization mechanism. An assembly of the soft manipulator 116, 216, 316 and the stabilization mechanism 114, 214, 314 may then be attached to a catheter 104, 204, 304. The catheter 104, 204, 304 may include a section of catheter tubing, the catheter tubing defining the working channel 110, cables, for examples the Bowden cables, of the stabilization actuator 126, 226, 316, and the multiple fluidic lines 112, 312. The cables, the catheter tubing, and the multiple fluidic lines 112, 312 may be enclosed with a section of single lumen extrusion or braid-reinforced tubing. The working channel may be used to deploy conventional interventional devices such as guidewires and catheters.

[0124] The proximal end 106, 206, 306 of the catheter 104, 204, 304 may include a custom- developed hub 124, 224, 324. The hub may split the cables and the multiple fluidic lines 112, 312 from the catheter 104, 204, 304, the multiple fluidic lines 112, 312 configured to interface with an actuation system, for example, the actuation system 128 of FIG.1, which may include custom syringe pumps as illustrated in FIG.30. The cables may be routed to the stabilization actuator 126, 226,326, the stabilization actuator including a syringe with a cable lock, for example, the cable lock 240 which may include a Luer lock valve connector. By pulling the syringe and locking the valve, the cables are clamped, thereby locking the stabilization mechanism 114, 214, 314 in its deployed position, as illustrated in FIG.2. - 17 - 4088749.v26200.2002002 (BU-2023-001)

[0125] FIG.3B illustrates the device of FIG.3A inserted through a blood vessel 334 using an introducer sheath 305. As illustrated, the catheter of the device 302 can be inserted through the introducer sheath 305 for transvenous access to an anatomical location, for example, the right atrium 335 of a heart. The introducer sheath 305 may be a 24 Fr, or 8 mm, introducer sheath, which may be commonly placed in peripheral vasculature to guide instruments toward more central vascular or intracardiac targets. The introducer sheath 305 may be inserted in upper thoracic vasculature, for example, a jugular or subclavian vein, or through other anatomical access locations, for example, femoral access locations. The introducer sheath 305 provides a continuous channel from an incision site, for example, on an upper thorax of a patient to a termination point of the introducer sheath 305 in the vessel 334, for example, a superior vena cava (SVC), just before the right atrium 335. The device 302 may be introduced through the introducer sheath 305. Once in position, the device 302 extends beyond the introducer sheath 305 and deploys stabilization using the stabilization mechanism 314 to increase operational stability of the soft manipulator 316 within the right atrium 335. The soft manipulator 316 may guide an interventional device to a location within the right atrium 335 to perform the endoluminal procedure.

[0126] FIG.4 illustrates an example approach for performing an endoluminal beating-heart procedure with an inset showing a magnified view of a heart. A device 402, for example, the devices 102, 202, 302, may be inserted through a peripheral access site, which may include a right internal jugular vein 433a or a left subclavian vein 433b. The device 402 may have a stabilization mechanism 414 in an undeployed state and a soft manipulator 416. The device 402 could be navigated from the subclavian access point through a body lumen 434, the device accessing the right atrium 435 of a heart through a superior vena cava.

[0127] The device 402 is small enough to access the heart via vasculature and has an ability to expand and exploit the larger cardiac workspace allows for stability, dexterity, and force output despite a motile environment and distant operation. The device 402 is also capable of stabilizing against the vasculature proximal to the heart and actively steering instruments within the heart. The device 402 further comprises millimeter-scale deployable mechanisms that address the scale discrepancy, moving workspace, and distant tool operation challenges. Specifically, device 402 features the stabilization component 414 that combines semirigid and flexible materials into a structure that expands and braces at a venous entrance to the heart. The device 402 was designed to provide leverage to an active steering component, for example the soft - 18 - 4088749.v26200.2002002 (BU-2023-001) manipulator 416, while minimizing physiological stresses such as blood pressure gradient in access vessels and vascular damage.

[0128] FIGS.5A-C generally illustrate example procedures in the right atrium of a beating heart using endoluminal devices. FIG.5A illustrates an example conventional endoluminal device 502a in the right atrium 535a of a heart without stabilization within a body lumen 534a. The device 502a may be limited in applying forces and accurately controlling position due to an intrinsic flexibility of the device 502a.

[0129] FIG.5B illustrates a device 502b similar to the devices 102, 202, 302. The device 502b comprises a stabilization mechanism 514b and a soft manipulator 516b. The stabilization mechanism 514b may stabilize a catheter (not shown) of the device 502b in a body lumen 534b. The soft manipulator 516b may be actuated to guide an endoluminal procedure, for example, an annular repair for a tricuspid valve.

[0130] FIG.5C illustrates a device 502c similar to the devices 102, 202, 302. The device 502c comprises a with a stabilization mechanism 514c and a soft manipulator 516c. The stabilization mechanism 514c may stabilize a catheter (not shown) of the device 502c in a body lumen 534c. The soft manipulator 516c may be actuated to guide an endoluminal procedure, for example, a coronary sinus lead placement.

[0131] FIGS.6A-C generally illustrate an example beating heart procedure using a device for performing a stabilized endoluminal procedure. FIG.6A illustrates an example embodiment of a device 602a navigating through a body lumen to the right atrium of a heart. The device 602a may be similar to devices 102, 202, 302 but having a stabilization mechanism 614a with multiple stabilization elements. The stabilization mechanism 614a is coupled to a catheter 604a. The device 602a further includes a soft manipulator 616a in a collapsed state, the soft manipulator 616a disposed at a distal end 608a of the catheter 604a. The device 602a is navigated through a body lumen 634a to the right atrium 635a of a heart.

[0132] FIG.6B illustrates a device 602b similar to the device 602a of FIG.6A. The device 602b includes a stabilized mechanism 614b in a deployed state coupled to a catheter 604b. The stabilization mechanism 614b is in a deployed state, stabilizing the catheter 604b against a body lumen 634b. The device 602b further includes a soft manipulator 616b in an actuated state, the soft manipulator 616b disposed at a distal end 608b of the catheter 604b. The soft manipulator 616b is positioned in the right atrium 635b of a heart

[0133] FIG.6C illustrates a device 602c similar to the device 602a of FIG.6A. The device 602c includes a stabilization mechanism 614c coupled to a catheter (not shown but similar with - 19 - 4088749.v26200.2002002 (BU-2023-001) respect to the catheter 604b). The stabilization mechanism 614c is in a deployed state, stabilizing the catheter in a body lumen 634c. The device 602c further includes a soft manipulator 616c in an actuated state, the soft manipulator 616c disposed at a distal end of the catheter. The soft manipulator 616c is configured to guide an endoluminal device 638, e.g., an annuloplasty coil, to perform an endoluminal procedure.

[0134] FIG.7A illustrates an example embodiment of a stabilization mechanism 714a of a device 702 similar to the devices 102, 202, 302. The stabilization mechanism 714a may be similar to the stabilization mechanism 114, 214, 314 and is coupled to a catheter 704a and may be configured to change between an undeployed state 714a-1 or a deployed stated 714a-2. The stabilization mechanism 714a may further include a rigid backbone 715a, and the rigid backbone 715a may define a working channel 717a and may be configured to carry multiple fluidic lines 719a. The working channel 717a and multiple fluidic lines 719a of the rigid backbone 715a may be in communication with a working channel and multiple fluidic lines, respectively, of a catheter, for example, the working channel 110 and the multiple fluidic lines 112 of the catheter 104 illustrated in FIG.1.

[0135] The stabilization mechanism 714a may further include of a fixed end 746a statically coupled to the catheter 704a and a moveable end 747a configured to move relative to the fixed end. The stabilization mechanism 714a may still further include multiple beams 748a extending between the fixed end 746a and the moveable end 747a. The moveable end 747a is further configured to slide towards the fixed end 746a in the deployed state 714a-2 causing the multiple beams 748a to bend at least in a radial direction.

[0136] FIG.7B illustrates another example embodiment of a stabilization mechanism 714b similar to the stabilization mechanism 614a. The stabilization mechanism 714b may include a first stabilization element 713-1 and at least a second stabilization element 713-2. The stabilization mechanism 714b may be configured to change between an undeployed state 714b-1 or a deployed stated 714b-2. The stabilization mechanism 714b may further include a rigid backbone 715b.

[0137] FIG.8 illustrates an example embodiment of a device for performing a stabilized endoluminal procedure navigating through a body lumen 834 to the right atrium 835 of a heart, in which the system includes multiple deployed stabilization elements. The device 802 may be similar to the device 102, 202, 302 and comprises a catheter 804 with a proximal end (not shown but similar with respect to the proximal end 106, 206, 306) and a distal end 808. The device 802 may be coupled with a stabilization mechanism 814 with multiple stabilization elements - 20 - 4088749.v26200.2002002 (BU-2023-001) configured to stabilize the catheter 804 in the body lumen 834. The device 802 may enable access to an anatomical region of the body, for example, the right atrium 835 of a heart.

[0138] FIGS.9A and 9B generally illustrate an experiment and findings thereof to evaluate the effect of a stabilization mechanism similar to the stabilization mechanism 114, 214, 314 on a flow of liquid through a lumen, for example the body lumen 434. The experiment is indicative of the stabilization mechanism’s physiological compatibility with respect to flow pressure and stress concentrations resulting from deployment of the stabilization mechanism. The pressures in the right atrium of a heart are in a range of approximately 5-8 mmHg, and extended pressure buildup can lead to hemorrhage in smaller cranial blood vessels. In addition, a saphenous vein, which is similar in mechanics to a superior vena cava, experiences circumferential failure at a stress of 1.8 MPa. Pressure drops caused by the stabilization mechanism is experimentally determined using the experiment shown in FIGS.9A and 9B by activating the stabilization mechanism in a section of silicone tubing with a pressure sensor on an upstream end and a downstream end.

[0139] FIG.9A illustrates an example experiment to evaluate the effect of a stabilization mechanism on a flow of liquid through a lumen. The experiment includes a tube 934, an upstream sensor 950-1, and a downstream sensor 950-2. The tube 934 is configured to enable a direction flow of a fluid and a stabilization mechanism is deployed in a test section 949 of the tube. Pressure measurements are acquired at the upstream sensor 950-1 and the downstream sensor 950-2.

[0140] FIG.9B illustrates findings of the experiment of FIG.9A. Specifically, FIG.9B illustrates pressure readings at the upstream sensor and the downstream sensor for the tube when no stabilization mechanism is present or when a deflated balloon, an inflated balloon, an undeployed stabilization mechanism, or a deployed stabilization mechanism is present. The left bar for each pair of bars in the plot of FIG.9B indicates pressure measurements at the upstream sensor 950-1 and the right bar indicates pressure measurements at the downstream sensor 950-2.

[0141] The baseline pressure, that is, when no stabilization mechanism is present, values at the upstream and downstream sensors were 6.13 ± 0.28 mmHg and 5.78 ± 0.28 mmHg, respectively. A generic balloon catheter was then tested as a control in its deflated and inflated states. The deflated balloon catheter’s pressure values were 7.05 ± 0.29 mmHg upstream and 7.27 ± 0.30 mmHg downstream, while the values when inflated ere 7.26 ± 0.27 mmHg upstream and 0 downstream. This drastic gradient arose because the inflated balloon completely cut off flow from the downstream pressure sensor. The undeployed stabilization mechanism’s pressure - 21 - 4088749.v26200.2002002 (BU-2023-001) values were 6.33 ± 0.27 mmHg upstream and 6.25 ± 0.24 mmHg downstream, while the values of the deployed stabilization mechanism were 6.60 ± 0.26 mmHg upstream and 6.30 ± 0.34 mmHg downstream. For both the deployed stabilization mechanism and the undeployed stabilization mechanism, the absolute pressure values range from 3.3 to 9.0% higher than the respective baseline values, and the pressure drops do not exceed the baseline pressure drop.

[0142] Further experiments were conducted to assess the effect of a device similar to the device 102, 202, 302 on the fluidic resistance, demonstrating negligible obstruction to blood flow caused by the device.

[0143] FIGS.10A and 10B generally illustrate experiments and results thereof evaluating a stabilization mechanism’s ability to generate mechanical leverage for the soft robot. To do this, a stabilization mechanism similar to the stabilization mechanism 114, 214314 is deployed in an explanted section of porcine superior vena cava.

[0144] FIG.10A illustrates an example experiment and results thereof for measuring reaction forces of a stabilization mechanism 1014a deployed in a body lumen 1034a, for example, an ex vivo porcine superior vena cava. A device 1051a is configured to apply a force on the stabilization mechanism 1014a from an axial direction and a force-torque sensor 1050a mechanically coupled to the device 1051a is configured to measure the force applied. The force applied versus a displacement distance is illustrated in plot 1052a. The stabilization mechanism withstood 3.63 ± 0.11 N of axial force at 2 mm of displacement

[0145] FIG.10B illustrates an experiment and results thereof for measuring reaction forces of a stabilization mechanism 1014b deployed in a body lumen 1034b, for example, an ex vivo porcine superior vena cava. A device 1051b is configured to apply a force on the stabilization mechanism 1014b from a radial direction and a force-torque sensor 1050b mechanically coupled to the device 1051b is configured to measure the force applied. The force applied versus a displacement distance is illustrated in plot 1052b. The stabilization mechanism withstood 0.98 ± 0.02 N of radial force at 5 mm of displacement.

[0146] FIG.11A and 11B generally illustrate experiments and results thereof evaluating forces applied on a body lumen by a stabilization mechanism similar to the stabilization mechanism 114, 214, 314. The experiments further indicate safety the stabilization mechanism when stabilizing against a blood vessel, for example, a superior vena cava, when actuating the stabilization actuator by pulling a cable in the stabilization actuator, e.g., a Bowden cable, by a pre-determined length, for example, 15 mm. The experiment was performed twice: once with a central axis of the stabilization mechanism fixed and once with a device similar to the device - 22 - 4088749.v26200.2002002 (BU-2023-001) 102, 202, 303 with the stabilization mechanism deployed in a silicone tube to allow for radial translation. ABAQUS simulations were performed using experimentally determined forces as inputs to simulate theoretical stress concentrations on the blood vessel, for example, the superior vena cava.

[0147] FIG.11A illustrates an example experiment and results thereof measuring forces generated on a sensor 1150a by a stabilization mechanism 1114a versus tension in a stabilization actuator (not shown but may be similar with respect to the stabilization actuator 126, 226) mechanically coupled to the stabilization mechanism 1114a. The stabilization actuator 1114a is configured in an affixed position and the stabilization actuator 1114a is deployed over a period of time by the stabilization actuator. The forces measured by the sensor 1150a and shown in FIG. 11A reflected the tension on a cable 1152a-1 and the forces 1152a-2 generated on the sensor 1150a are illustrated in a plot.

[0148] FIG.11B illustrates an example model of stress concentration areas for maximum experimental force generated by a stabilization mechanism. The maximum experimental force generated by the stabilization mechanism is acquired from the experiment of FIG.11A. Simulations are performed in ABAQUS to evaluate theoretical stress application of a stabilization mechanism in a deployed state on walls of a body lumen. Mechanical properties of the walls of the body lumen simulated are approximated based on properties of a porcine saphenous vein.

[0149] As illustrated in the plot 1152a, a maximum Bowden cable tension of 1.91 N, the stabilization mechanism generates 1.21 N of radial force. The radial force yields simulated maximum stress concentrations of 0.898 MPa on the body lumen. The maximum stress value represents a theoretical maximum based on idealized testing conditions with a rigid force sensor and a central axis of the stabilization mechanism affixed. In a more realistic scenario, the stabilization mechanism’s central axis would not be fixed, and elasticity of the body lumens would dissipate some of the stress resulting from mechanical strain. A similar simulation is performed to emulate this, in which the stabilization mechanism is placed in a silicone test section, allowing the central axis to translate radially upon contact with the walls and the force sensor. In this case, a maximum cable tension of 4.99 N yields only 0.43 N of radial force from the stabilization mechanism. Based on these results, the simulated maximum stress concentration of 0.212 MPa on the vein. Given that the saphenous vein fails circumferentially at 1.8 MPa, the forces applied would not induce failure. An experimental procedure was performed in which the - 23 - 4088749.v26200.2002002 (BU-2023-001) stabilization mechanism was deployed in a section of porcine superior vena cava over one 4-hour session. No visible signs of damage from the stabilization mechanism were present.

[0150] FIG.12 illustrates an example embodiment of a rigid backbone 1215 of a stabilization mechanism 1214, with an inset showing a magnified view of the rigid backbone 1215. A device 1202, similar to the device 102, 202, 302, comprises a catheter and the stabilization mechanism 1214 with the rigid backbone 1215. Beams, similar to the multiple beams 748a, of the stabilization mechanism 1214 are not illustrated. The device 1202 further comprises a soft manipulator 1216 disposed at a distal end 1208 of the catheter 1204. The rigid backbone 1215 may define a working channel (not shown but similar with respect to the working channel 717a) and may be configured to carry multiple fluidic lines 1219. The working channel and multiple fluidic lines 1219 of the rigid backbone 1215 may be in communication with a working channel and multiple fluidic lines, respectively, of a catheter, for example, the working channel 110 and the multiple fluidic lines 112 of the catheter 104 illustrated in FIG.1. The stabilization mechanism may be mechanically coupled to a stabilization actuator (not shown but similar with respect to the stabilization actuator 126, 226, 326) using at least one cable, for example, the Bowden line 1221. The stabilization actuator may be further configured to deploy the stabilization mechanism by applying a force, for example a tension, to the at least one cable. The rigid backbone 1215 and the stabilization mechanism 1214 in an undeployed state may have an outer diameter sufficiently small to enable navigation through a body lumen, for example, less than 8 mm.

[0151] FIG.13A illustrates an example fabrication process for a stabilization mechanism including multiple sheets of material. First, individual sheets of semirigid spring steel (SS) 1354- 1 and flexible polyimide 1354-2, for example, Kapton, film are laser cut. The individual sheets are layered and adhered using a biocompatible pressured activated adhesive to create a laminate 1356a-1 with two layers of the spring steel sandwiching a single layer of the polyimide. The laminate is coated with a soft thermoplastic polyurethane (TPU) layer 1354-3 before being excised, for example, being laser cut 1355, from the sacrificial material to create an excised laminate 1356a-2. The primary purpose of the TPU layer 1354-3 is to soften edges of steel joints to reduce stress concentrations imparted on a body lumen. The excised laminate 1356a-2 consists of six flexure joints oriented parallel to each other and connected at either end. The excised laminate is wrapped around a rigid backbone 1315a, for example, a stereolithography (SLA)- printed multi-lumen tube using biocompatible resin. The multi-lumen tube accommodates the three fluidic tubing lines used to actuate the soft robot and two Bowden cables used to deploy the - 24 - 4088749.v26200.2002002 (BU-2023-001) stabilization mechanism. The resulting stabilization mechanism expands to 32 mm in diameter in a deployed state and collapses to 8 mm in diameter in an undeployed state. The TPU coat 1354-3 serves a secondary purpose during deployment as a store for elastic energy. This provides a restorative force that causes the stabilization mechanism to default to the undeployed state during nondeployment. When in the deployed state, the stabilization mechanism assumes a wireframe- like structure with a cumulative cross-sectional area ≤50% that of a body lumen, for example, a superior vena cava, allowing continued blood flow through the body lumen. The stabilization mechanism changed into the undeployed state for removal of a device with the stabilization mechanism or reorientation of a soft manipulator of the device.

[0152] FIG.13B illustrates an additional example fabrication process for a stabilization mechanism including a single sheet of material. The additional example fabrication process utilizes a single sheet 1356b-1 of super-elastic Nitinol. The stabilization mechanism is laser cut from the single sheet of Nitinol. A custom-threaded mandrel 1357-1 and lock nuts 1357-2 are used to wrap and hold the stabilization mechanism to form an assembly 1358. The assembly is placed in a furnace set to 550 degrees Celsius for 10 minutes. The mandrel is pulled from the furnace and quenched in water. The stabilization mechanism 1314b is removed from the mandrel before wrapping around a rigid backbone 1315b.

[0153] The stabilization mechanism 1314a is configured to expand to stabilize a device similar to the device 102, 202, 302 within a body lumen or against a blood vessel. However, the hinged design may experience buckling due to off-center loads an excessive actuation. In a clinical environment, buckling could lead to point contacts against the vasculature walls and high stress concentrations. The stabilization mechanism 1314b may improve performance, robustness, safety, and compatibility of the stabilization mechanism 1314b. A continuous beam design allows for greater predictability in the stabilization mechanisms 1314b bending behavior as well as avoided concavities. Nitinol also increases the mechanisms robustness given the material’s high fatigue resistance and robustness against tearing. Nitinol further demonstrates excellent biocompatibility and is an established material in various endoluminal applications, such as stents. Studies have shown nitinol-based devices can be deployed within the body on the timescale of years without causing adverse reactions.

[0154] Unlike a hinged design, continuous elastic beams, such as the beams of the stabilization mechanism 1314b, eliminate possibilities of joints moving in unintended directions, which may cause point contacts with the vasculature and high stress concentrations. However, the beam’s bending curvature also presents a potential for a small area of contact due to uniform - 25 - 4088749.v26200.2002002 (BU-2023-001) curvature during bending, also raising stress concentrations. To increase venous contact area, a width at a center of each beam is increased, flattening the center section’s profile. This geometric change increases the second moment of inertia at the center portion to crease resistance to bending.

[0155] As previously described, the soft manipulator 116, 216, 316 may be part of a class of soft robot manipulators called a stacked balloon actuator (SBA). The SBA architecture provides several advantages, including a large expansion ratio and high force generation. Because these actuators are fabricated by subjecting a 2D laminate, for example, of TPE (thermoplastic elastomer) and polytetrafluoroethylene (PTFE; Teflon), to heat and pressure, they can be fully collapsed in the axial direction. However, depending on the number of layers used, the inflatable balloon geometry can expand to an arbitrarily large length. For example, a soft manipulator similar to the soft manipulator 116, 216, 316 may include three stacked balloon actuators, similar to the multiple actuators 118 comprising 20 balloons positioned radially around a 6-Fr central channel, for example the guided working channel 122. Inflatable chambers defined by the three stacked balloon actuators, similar to the inflatable chambers 122, may have respective longitudinal axes that fall on respective vertices of an equilateral triangle. The stacked balloon actuators can inflate from a deflated thickness of approximately 1 mm to an extended state, for example, 4 cm, without compromising a cross-sectional area of the central channel. Prior works have shown that the SBA can generate forces up to several newtons in bending and extension when actuated, for example, to an internal pressure of 100 kPa.

[0156] While the SBA may be configured to naturally collapse along a main (longitudinal) axis, delivery through the vasculature necessitates an additional ability to radially collapse to pass through a body lumen, for example, to a diameter of 18 Fr or 24 Fr. To achieve this radial collapse, the SBA may be inflated equally in all chambers to fully elongate. A tip of the SBA may be manually fixed to a constant length while a vacuum is applied to the inflatable chambers. The applied vacuum may normally cause the chambers to fold axially according to their embedded geometry, but the fixed length may cause them to buckle and collapse radially. Previous works have demonstrated that a three-chamber SBA with a nominal diameter of 15 mm can radially collapse to a minimum diameter of 4.5 mm

[0157] FIGS.14A-C generally illustrate an example embodiment of a soft manipulator in various states of actuation. FIG.14A illustrates an example embodiment of a soft manipulator 1416a similar to the soft manipulator 116, 216, 316 in a collapsed state. FIG.14B illustrates an example soft manipulator 1416b similar to the soft manipulator 1416a but configured in a bent - 26 - 4088749.v26200.2002002 (BU-2023-001) actuation state. FIG.14C illustrates an example soft manipulator 1416c similar to the soft manipulator 1416a but configured in an extended actuation state.

[0158] FIG.15A illustrates another example embodiment of a soft manipulator 1516a with a bean-shaped stacked balloon actuator 1518a in a bent actuation state. The soft manipulator 1516a may be similar to the soft manipulator 116, 216, 316. The soft manipulator 1516a may include multiple soft balloon actuators 1518a configured in a concave design, for example, in a bean shape, which may provide a guided working channel 1522a with a larger diameter while preserving an outer diameter size of the soft manipulator 1516a.

[0159] FIG.15B illustrates another example embodiment of a soft manipulator 1516b with multiple circular stacked balloon actuators 1518b in a bent actuation state. The soft manipulator 1516b may be similar to the soft manipulator 116, 216, 316. The soft manipulator 1516b may include multiple soft balloon actuators 1518b configured in a circular design, which may provide a guided working channel 1522b.

[0160] Comparing the soft manipulator 1516a and the soft manipulator 1516b, the design of the soft balloon actuators 1518a provide a larger working diameter for the guided working channel 1522a than is achievable by the circular soft balloon actuators 1518b while maintaining a similar outer diameter size of the soft manipulator.

[0161] FIG.16 illustrates an example diagram of a soft manipulator 1616 similar to the soft manipulator of FIG.15A in a cross-sectional view. Dimensions of the soft manipulator 1616 were optimized based on upon constraints placed sizes of lumens, including body lumens. In an example embodiment of the soft manipulator 1616, the outer diameter may be Ø1= 15 mm and the diameter of the guided working channel 1620 may be Ø2= 4 mm. An offset distance, for example, t = 0.75, between a stacked balloon actuator 1618 and the guided working channel 1622 may ensure proper bonding of constituent thermoplastic layers of the soft balloon actuator 1616. A minor diameter that defines a size of the stacked balloon actuator 1618 may be set to Ø3= 4 mm.

[0162] FIGS.17A-C generally illustrate an example experiment and results thereof evaluating force transmission by a soft manipulator of a stabilized device on a sensor. Because puncture of an atrial septum, which is composed of tougher tissues than the tricuspid valve annulus, during a tricuspid valve annulation procedure can require forces of ≈1 N, the force transmission of the device is evaluated in multiple poses.

[0163] FIG.17A illustrates an example experiment for measuring force transmission by a soft manipulator 1716a of a stabilized device 1702. The device 1702 includes a stabilization - 27 - 4088749.v26200.2002002 (BU-2023-001) mechanism 1714a in a deployed state, the stabilization mechanism 1714 stabilizing a catheter 1704 within a body lumen 1734. The device further includes the soft manipulator 1716a, the soft manipulator 1716a actuated to apply a force on a force-torque sensor 1750. After the stabilization mechanism 1714 has been deployed, as illustrated in FIG.17A, the soft manipulator 1716a is maneuvered toward an acrylic target connected to the sensor 1750 in four configurations. The soft manipulator 1716a is configured to apply a pressure on the sensor 1750 until an internal pressure of 120 kPA causes an actuation system (not shown but similar with respect to FIG.27) of the soft manipulator to stall. Once the soft manipulator 1716a has made contact with the sensor 1750, volumes of soft balloon actuators of the soft manipulator 1716a are held constant. Forces applied to the sensor 1750 are measured over the course of this experiment.

[0164] FIG.17B illustrates measurements of force transmission over time for the soft manipulator of 17A at two extended actuation states. The two extended states of the soft manipulator include a 2-cm extension state 1716b-1, with corresponding plot of force transmission over time 1752-1, and a 4-cm extension state 1716b-2, with corresponding plot of force transmission over time 1752-2. The soft manipulator generated a maximum force of 1.84 ± 0.05 N in the 2-cm extension state 1716b-1 and 0.94 ± 0.03 N in the 4-cm extension state.

[0165] FIG.17C illustrates measurements of force transmission over time for the soft manipulator of FIG.17A at two bent actuation states. The two bent actuation states include a 30- degree bending state 1716c-1, with corresponding plot of force transmission over time 1752-3, and a 45-degree bending state 1716c-2, with corresponding plot of force transmission over time 1752-4. In both states, the sensor was placed 3 cm from a base of the soft manipulator. The soft manipulator generated a maximum force of 0.87 ± 0.05 N in the 30-degree bending state 1716c-1 and 0.74± 0.01 N in the 45-degree bending state 1716c-2.

[0166] When the volumes of the soft balloon actuators of the soft manipulator 1716a are held constant, a decrease in force transmission is observed in all cases. In the two extended actuation states, the force transmission decreased by 11.1% over 1.9 s in the 2-cm extension state 1716b-1 and 6.3% over 2.4 s in the 4-cm extension state. In the two bent actuation states, the force decreased by 11.2% over 1.8 s in the 30-degree bending state 1716c-1 and 8.1% over 1.8 s in the 45-degree bending state 1716c-2. This decrease may be indicative of viscoelastic material behavior in the porcine superior vena cava sample

[0167] FIGS.18A and 18B illustrate bend angles of an example soft manipulator 1816a, 1816b actuated using one inflatable chamber and using two inflatable chambers, respectively. The soft manipulator 1816a, 1816b may be similar to the soft manipulator 116, 216, 316. - 28 - 4088749.v26200.2002002 (BU-2023-001) Extremes of the soft manipulator’s 1816a, 1816b task space with an endoluminal device, for example a flexible 0.35-mm guidewire 1838a, 1838b inserted through a guided working channel of the soft manipulator 1816a, 1816b are illustrated. For the soft manipulator 1816a, an inflatable chamber (not shown but similar with respect to a chamber of the multiple inflatable chambers 120) is inflated while two chambers are kept deflated, enabling a bend angle of 200-degrees. For the soft manipulator 1816b, two inflatable chambers are inflated while one chamber is kept deflated, enabling a bend angle of 207-degrees. In addition, the soft manipulator 1816a, 1816b demonstrated a radius of curvature of 7.6 mm.

[0168] FIG.19 illustrates an example experiment and results thereof evaluating a combined stiffness of a soft manipulator 1916 and an endoluminal device, for example, a guidewire 1938, deployed through the soft manipulator. The soft manipulator 1916 is inflated to a 4-cm extended state and a stiff end of the guidewire 1938 is inserted through the soft manipulator 1916. Measurements are acquired by a force-torque sensor 1950 configured to apply a force on the guidewire 1938. A plot illustrates the measurements of forces applied by the sensor 1950 on the guidewire 1938 versus a displacement distance. Measurements are acquired for the soft manipulator 1916 with a tool guide (which may be similar to the tool guide 236 of FIG.2) 1952- 1 and without the tool guide 1952-2. With the tool guide, the soft manipulator 1916 and the guidewire 1938 had a stiffness of 6.3 mN / mm. Without the tool guide, the guidewire 1936 had more freedom to move in the soft manipulator’s 1916 central channel, decreasing the stiffness to 5.0 mN / mm.

[0169] FIG.20A illustrates a deployment angle of an example embodiment of an endoluminal device, for example, a guidewire 2038a, using an example soft manipulator 2016a with a tool guide 2036. The soft manipulator 2016a may be similar to the soft manipulator 116, 216, 316. The soft manipulator 2016a is actuated to 90° in bending and the tool guide 2036 maintained the guidewire 2038a at an angle of 97.8° from horizontal. FIG.20B illustrates a deployment angle of an example embodiment of an endoluminal device 2038b using an example soft manipulator 2016b without a tool guide. The soft manipulator 2016b may be similar to the soft manipulator 2016a, but without the tool guide 2036. Without the tool guide, the guidewire 2038b is free to bend 114.2° from horizontal.

[0170] A tool guide, e.g., the tool guide 2036, disposed at a tip or a face of a soft manipulator, e.g., the soft manipulator 2016a, may increase a stiffness of the tip of the soft manipulator and guides delivery of an interventional device, e.g., the guidewire 2038a, 2038b, by - 29 - 4088749.v26200.2002002 (BU-2023-001) promoting orthogonality of the interventional device passing through a guided working channel with respect to the face of the soft manipulator.

[0171] FIG.21A illustrates an example computer-simulated model of a device 2102 in the right atrium 2135 of a heart. The device includes a soft manipulator 2116 and a stabilization mechanism 2114 in a deployed state. The model of the heart is created by segmenting a computed tomography (CT) scan of a heart in Mimics Innovation Suite (Materalise) and includes the right atrium 2135, a superior vena cava 2134, a coronary sinus 2137, and a tricuspid valve 2139. FIGS.21B and 21C illustrates task spaces of the soft manipulator 2116 in the computer- simulated model of FIG.21A in the right atrium of the heart. The task space may be experimentally determined from a soft manipulator similar to the soft manipulator 2016a, 2016b and is overlaid upon the computer-generated model of the right atrium 2135 of FIG.21A, demonstrating an ability to position the soft manipulator 2116a in clinical relevant positions. Further, FIGS.21B and 21C illustrate the task spaces achieved by the soft manipulator 2116 when the stabilization mechanism 2114 is deployed in a different position.

[0172] FIG.22 illustrates an example experiment for navigating a device 2202 for performing a stabilized endoluminal procedure to a number of predetermined locations. The device 2202 may be similar to the device 102, 202, 302. The device 2202 includes a soft manipulator 2216 and a stabilization mechanism 2214. The device is positioned in a section of tubing 2234 mimicking a body lumen and the stabilization mechanism 2214 is configured in a deployed state. For the experiment, the soft manipulator 2216 guides a 0.9-mm guidewire 2238 through five holes 2260, each hole of the five holes 1 cm in diameter, cut into a piece of acrylic 2261 placed 4 cm from the base of the soft manipulator 2216. The trial is timed and completed in just over 1 min and a half with the device operated by a single user.

[0173] FIG.23 illustrates an example device 2302 for performing a stabilized endoluminal procedure navigating a bend in a model 2334 of a body lumen, with an inset showing a top-down view of the device navigating the bend. The device 2302 may be similar to the device 102, 202, 302 and includes a catheter 2304 with a distal end 2308, a stabilization mechanism 2314 coupled to the catheter 2304, and a soft manipulator 2316 disposed at a distal end of the catheter 2308. The device 2302 is demonstrated to fit through peripheral vasculature, e.g., a subclavian vein, to access the right atrium. The device 2302 is inserted into a model 2334 comprising a section of tubing and a stereolithography-printed (Formlabs, Flexible 80A) semisoft right atrium. The device 2302 demonstrates sufficient flexibility to conform to the curved path, traversing a ≈90° turn. - 30 - 4088749.v26200.2002002 (BU-2023-001)

[0174] Interventional tool delivery through a device similar to the device 102, 202, 302 requires a continuous center channel to the hub 126, 226, 326 with a tip of the soft manipulator 116, 216, 316. Achieving this continuity necessitates a center channel, for example, the guided working channel 122 that can grow in length in parallel with the soft manipulator 116, 216, 316, maintaining dexterity inside a heart.

[0175] FIG.24A illustrates an example soft manipulator 2416 with a collapsible tubing 2462a configured to define a guided working channel 2222. The collapsible tubing 2462a may be configured to collapse and to extend with the soft manipulator 2416. The collapsible tubing’s 2462a wall thickness of approximately 0.5 mm decreases a diameter of the guided working channel 2222 of the soft manipulator 2416. For the soft manipulator 2416, the guided working channel’s 2222 diameter, for example, of 3 mm, or 9 Fr, is still sufficient to accommodate 7-8 Fr catheters used in standard practice.

[0176] FIG.24B illustrates the collapsible tubing of FIG.24A in a collapsed state 2462b-2 and an extended state 2462b-1. The collapsible tubing may include stiff collars 2463 and flexible sections 2464 in an alternating configuration. Flexible sections 2464 are configured to collapse when the collapsible tubing is in the collapsed state 2462b-2.

[0177] FIG.24C illustrates example modeled kinematics of a segment of the collapsibletubing of FIGS. 24A and 24B. A set of variables [^^, ^^] is derived for a single segment of thecollapsible tubing in two dimensions (2-D), wherein:

[0178] Based on these parameters, the modeled kinematics of the single segment in 2-D are:^^ = ^ cos (^^)^^^ ^[sin (^^)]^^ = 180 − 2^^^^ = cos(^^) sin (^^)^^^ ^^[− sin (^^)]

[0179] pseg is a position of {Sb,i} with respect to and Rseg is an orientation of {Si}with respect to {Si-1}. Rsegis parameterized by α, which is an angle between an x-axis of {Si-1} and an x-axis of {Si}. - 31 - 4088749.v26200.2002002 (BU-2023-001)

[0180] The modeled kinematics of the single segment, for example, a local segment, of the collapsible tubing can be expanded into a global model. Globally, a pose of an ithsegment atframe {St,i} is given by:^^ ^ ^^ଶ௫ଶ ^^ = 1

[0181] Riis the orientation of the ithsegment at frame {Sb,i}, and pt,i is the position of the ithsegment at frame {St,i}these are parameterized by local kinematic variables Rsegand pseg. A global tip pose of the collapsible tubing may be calculated recursively using these relationships.

[0182] FIG.25 illustrates an example fabrication process for the collapsible tubing of FIGS. 24A and 24B. To fabricate the growing tubing, stiff collars similar to the stiff collars 2463 made of 72D Pebax tubing are placed in an incremental manner along a 42D Pebax tube and glued down (i). The 42D Pebax tube may form flexible sections similar to the flexible sections 2464. The stiff collars and the Pebax tube are placed concentrically over an aluminum mandrel and a heat shrink tubing is placed concentrically over the stiff collars and the Pebax tube (ii). Heat is applied at 165-degrees Celsius to the heat shrink tubing and the heat shrink tubing applies even pressure as its diameter decreases (iii). An end of the shrink tubing is snipped with scissors to allow it to be peeled off (iv). Collapsible tubing similar to the collapsible tubing 2462a can be released from the mandrel and can expand in contract in a manner consistent with previously described kinematics (v, vi).

[0183] FIG.26 illustrates an example embodiment of a soft manipulator 2616 with a sensor 2666, a magnet 2668, and conductive traces 2670. The soft manipulator 2616 may be similar to the soft manipulator 116, 216, 316. The sensor 2666 may be configured to monitor contact forces applied to the tip of the soft manipulator 2616, to monitor interaction forces and contacts with an anatomy of a heart to ensure safety and ease a procedure by relaying force feedback, and to complement imaging, for example, x-ray imaging, to increase accuracy of positioning of the soft manipulator within an anatomical location, for example a beating heart.

[0184] An example embodiment of the sensor 2666 may include a 2 mm by 2 mm by 0.75 mm barometer encapsulated in silicone such that, when forces are applied to the silicone, the forces are transmitted to the barometer diaphragm. Electrical signals can be routed to the sensor, - 32 - 4088749.v26200.2002002 (BU-2023-001) for example, the barometer, via a printed circuit board, which can be positioned at the tip of the soft manipulator 2616. The conductive traces 2670 may be fully embedded into material of the soft manipulator 2616, for example, thermoplastic layers, without altering kinematics of the soft manipulator 2616. In other embodiments, the thermoplastic layers may be disposed along the exterior of a soft manipulator similar to the soft manipulator 2616. The conductive traces may further be integrated on the soft manipulator 2616 without changes in resistance during inflation.

[0185] The magnet 2668, for example, a ring magnet or a disk magnet, may be useful in localizing the soft manipulator 2616 within an anatomical location and is further described in FIGS.29A and 29B.

[0186] FIG.27 illustrates an example embodiment of a soft manipulator 2716 with conductive traces 2770. The soft manipulator 2716 and the conductive traces 2770 may be similar to the soft manipulator 2616 and the conductive traces 2670 illustrated schematically in FIG.26.

[0187] FIG.28A illustrates an example embodiment of a sensor 2866a associated with a stabilization mechanism 2814a. The sensor 2866a can be a force sensor that is encapsulated in silicone. The sensor 2866a may be similar to the sensor 2666 described in the context of FIG.26. The sensor 2866a may be configured to sense forces associated with deployment of the stabilization mechanism 2814a within a body lumen. FIG.28B illustrates another example of an embodiment of a stabilization mechanism 2814b including conductive traces 2870b in a deployed (e.g., expanded) state. The conductive traces 2870a, 2870b may be similar to the conductive traces 2670 of FIG.26. The conductive traces 2870a, 2870b may be integrated into the stabilization mechanism 2814a, 2814b without altering the functionality of the stabilization mechanism 2814a, 2814b.

[0188] FIG.29A illustrates an example embodiment of a soft manipulator 2916a with a magnet 2968a positioned within a chamber of a heart 2935 and a magnetometer 2969 positioned external to a human body configured to measure a position of the magnet 2968. The soft manipulator 2916a and the magnet 2968 may be similar to the soft manipulator 2616 and the magnet 2668 illustrated schematically in FIG.26. The soft manipulator 2916a may be disposed at a distal end 2908 of a catheter 2904 of a device 2902 for performing a stabilized endoluminal procedure similar to the device 102, 202, 302. The device 2902 may further comprise a stabilization mechanism 2914 coupled to the catheter 2904 and configured in a deployed state to stabilize the catheter 2904 in a body lumen 2934. - 33 - 4088749.v26200.2002002 (BU-2023-001)

[0189] Being able to track a position of a device, for example, the device 2902, may be useful towards enabling clinical use of the device 2902. Magnetic localization has been used in multiple applications including capsule endoscopy and catheter guidance for wireless tracking of positions and orientation. Absolute magnetic localization of a tip of the soft manipulator 2916 of the device 2902 may be achieved by attaching the magnet 2968a, which may be small and less than 5 mm in diameter) to the soft manipulator 2916 and placing the magnetometer 2969, which may be an array of magnetometers on a surface of a patient’s body. The array of magnetometers may include, for example, six magnetometers uniformly distributed and may be fastened to a stationary object, for example, an operating table, to mitigate motion.

[0190] Machine Learning (ML) algorithms (e.g., long short-term memory (LSTM) and deep neural network (DNN) algorithms), in conjunction with analytical optimization methods including Dipole Model Based Optimization, modeling the magnet as a dipole at its center, will be used to infer a relative position and an orientation of the tip of the soft manipulator 2916a using the magnet 2668a.

[0191] FIG.29B illustrates example experimental results evaluating errors between localization of a soft manipulator 2916b at different actuation states using an electromagnetic tracker 2971 versus using a magnet 2968b and a magnetometer, which may be similar to the magnet 2968a and the magnetometer 2969 of FIG.29A. The experimental findings, as illustrated in FIG.29, indicate a positional accuracy of ±1 mm throughout the workspace described in the context of FIG.29A.

[0192] FIG.30 illustrates a controller 3032, control hardware 3030, and an actuation system 3028 for an example embodiment of a system 3000 for performing a stabilized endoluminal procedure, with an inset showing a magnified view of actuation components for a fluidic device. The actuation system 3028, the control hardware 3030, and the controller 3032 may be similar to the actuation system 128, the control hardware 130, and the controller 132, respectively, of FIG. 1. The system 3000 may comprise a device similar to the device 102, 202, 302. The system 3000 may further include the actuation system 3028 including multiple fluidic devices 3072 coupled fluidically with respective multiple fluidic lines, for example the fluidic lines 112 (FIG.1). The multiple fluidic devices 3072, for example, syringes, may be configured to inflate or deflate multiple respective inflatable chambers, for example, the multiple inflatable chambers 120 of the soft manipulator 116 (FIG.1), by injecting or extracting a fluid.

[0193] The system 3000 may further comprise the control hardware 3030, which may include a processor 3031 communicatively coupled with the actuation system 3028. The - 34 - 4088749.v26200.2002002 (BU-2023-001) processor 3031 may be communicatively coupled with multiple stepper motors 3074 in coupled arrangement with the multiple fluidic devices 3072 of the actuation system 3028. The multiple stepper motors 3074 may be configured to control injecting or extracting of the fluid by the respective multiple fluidic devices 3072. The processor 3031 may be a microcontroller, for example, an Arduino microcontroller.

[0194] As illustrated in FIG.30, a stepper motor of the multiple stepper motors 3074 may be coupled mechanically to a lead screw 3075 by a flexible shaft coupler 3076. A linear rail 3077 with a carriage block 3078 may be used to create a path with a travel length, for example, 100 mm. A push-block 3079 may be fastened to a carriage block 3078 and coupled to the lead screw 3075 using a brass nut 3080. This forms a linear stage actuation assembly. The push-block 3079 may be configured to hold a portion of a fluidic device of the multiple fluidic devices 3072. The fluidic device may be secured using a block lid 3081. A fluidic device retainer device 3082 and a fluidic retainer lid 3083 may be configured to hold statically the fluidic device. The actuation system 3028 may be enclosed within an acrylic box.

[0195] The processor 3031 may be further communicatively coupled to the controller 3032 configured to receive inputs from an operator. The processor 3031 may be further configured to operate the multiple stepper motors 3074 based on the inputs received from the operator on the controller 3032.

[0196] FIG.31 illustrates an example application of a system 3100 for performing a stabilized endoluminal procedure, wherein (i) actuation components of the system are placed on a table near a patient, enabling an operator to control (ii) a device of the system inserted into the patient through an incision site\e. The system 3100 may be similar to the system 100 of FIG.1 and may include a device 3102 with a catheter 3104. A hub 3124 may be disposed at a proximal end 3106 of the catheter 3104. A distal end, a stabilization mechanism, and a soft manipulator may be inserted into a patient 3186 and not illustrated, but may be similar to the distal end 108, the stabilization mechanism 114, and the soft manipulator 116. The hub 3124 may be configured to for passage of multiple fluidic lines 3112 to fluidically couple to an actuation system 3128. The system may further include control hardware 3130, which may include a processor similar to the processor 3031 of FIG.30 communicatively coupled to the actuation system 3128 and a controller 3132. The controller 3132 may be configured to receive inputs from an operator 3187. The system 3100 may be used in conjunction with other imaging and surgical systems, for example, a C-arm fluoroscopy machine. - 35 - 4088749.v26200.2002002 (BU-2023-001)

[0197] A system similar to the system 3100, as a soft robotic platform or as a robot, may assume the role of a conventional guiding sheath to conform with existing clinical workflows in a catheterization laboratory. Unlike conventional sheaths, though, a device of the system provides stable and active control over existing interventional tools to which clinicians are already accustomed. In doing so, the robot reduces procedural times and X-ray fluoroscopy exposure.

[0198] Ex vivo testing was performed to evaluate a device similar to the device 102, 202, 302 in the context of two exemplar procedures: tricuspid valve annular puncture and coronary sinus cannulation. The goals of the ex vivo experimentation were: (i) to evaluate the stabilization of a stabilization mechanism similar to the stabilization mechanism 114, 214, 314 within a body lumen, for example, a superior vena cava, (ii) to demonstrate the device’s ability to effectively perform in a fluidic environment, and (iii) to quantitatively assess outcomes pertaining to coronary sinus cannulation and tricuspid valve repair. The primary outcome was time to procedural completion. For coronary sinus cannulation, this was defined as the time required to navigate a soft manipulator, similar to the soft manipulator 116, 216, 316 toward a coronary sinus of the right atrium and to cannulate the coronary sinus with a guidewire. For tricuspid valve annular puncture, this was defined as the time required to navigate the soft manipulator toward the tricuspid valve annulus, puncture the annulus, and retract. The tricuspid valve annular puncture procedure represents a simplified version of a tricuspid valve annuloplasty procedure, in which anchors are placed around the tricuspid valve annulus and used to cinch it together with a secondary device. Because annuloplasty anchors and devices are proprietary and not standardized components, the tricuspid valve annular puncture is performed at a pre-determined location, which is paramount to success of an annuloplasty procedure. EXAMPLE 1 – IN-VITRO TRICUSPID VALVE ANNULAR PUNCTURE IN A DYNAMIC SYSTEM

[0199] Tricuspid valve regurgitation is a result of various valve disease etiologies, and even mild to moderate cases present a notable risk to patients. A common approach to its treatment is annuloplasty, in which the annular tissue is cinched together with sutures or partial rings. However, a minimally invasive approach to annuloplasty, which may involve the use of anchors to fasten an annuloplasty ring around the annulus, is challenging because of the tricuspid valve’s motility and proximity to the atrioventricular node of the conduction pathway. These procedural issues make stable force transmission paramount to success. A main purpose of the tricuspid valve annular puncture task is to simulate annuloplasty anchor placement by puncturing at a - 36 - 4088749.v26200.2002002 (BU-2023-001) predetermined location without damaging surrounding structures such as the tricuspid valve leaflets and applying consistent forces on a motile target. It was experimentally determined that 0.84± 0.12 N was sufficient to puncture the annular tissue.

[0200] FIG.32 illustrates an example experiment for performing a tricuspid valve annular puncture task using a device 3202 for performing a stabilized cardiovascular procedure. The device may be similar to the device 102, 202, 302. The device 3202 may comprise a catheter 3204 and a stabilization mechanism 3214 coupled to the catheter. The stabilization mechanism 3214 may be deployed in lumen 3234, for example, a section of porcine superior vena cava, mimicking a body lumen, a tricuspid valve annulus was punctured to simulate the device’s 3202 ability to insert an annuloplasty anchor. Individual trials consisted of insertion of the device 3202, stabilization in the lumen 3234 using the stabilization mechanism 1314, navigation of a soft manipulator 3216 toward the tricuspid valve annulus 3284, tricuspid valve puncture, and dye injection. An operator began by inserting the device 3202 into the lumen 3234 until a tip of the soft manipulator 3216 was partially extended past an opening of the lumen 3234. The device 3202 was inserted with the soft manipulator 3216 in a collapsed state and the stabilization mechanism 3214 was deployed after device positioning. The soft manipulator 3216 was then navigated toward the tricuspid valve annulus 32, positioned 3 cm away and at a 45° angle to a base of the soft manipulator 3216. The user delivered a needle through a guided working channel and a tool guide (not shown but similar with respect to the guided working channel 122 in FIG.1 and the tool guide 236 in FIG.2, respectively) to puncture the tricuspid valve annulus and deliver colored dye, indicating a successful puncture.

[0201] FIGS.33A-D illustrate example experiments using a device 3302 for performing a stabilized endoluminal procedure with a soft manipulator 3316 in collapsed states (FIGS.33A, 33C) and after successful puncture (FIGS.33B, 33D) for the experimental setup that is schematically illustrated in a horizontal configuration in FIG.32. FIGS.33A and 33B illustrate the experiment performed on an in vitro tricuspid valve 3384-1 made of silicone. FIGS.33C and 33D illustrate the experiment performed on an ex vivo explanted porcine tricuspid valve 3384-2. Both the in vivo experiment case and the ex vivo experiment case were performed for a static tricuspid valve and a beating tricuspid valve, the beating tricuspid valve configured to move using a linear motor (not shown) to simulate cardiac pacing at 60 beats per minute (bpm). A physiological amplitude of 6 mm oriented at 45° from the longitudinal axis of the device 3302 is used for the beating tricuspid valve. - 37 - 4088749.v26200.2002002 (BU-2023-001)

[0202] Different studies have measured different annular motion values depending on a reference plane, indicating complex, multidimensional motion of the tricuspid valve. Because the device 3302 is positioned in a relatively static vessel, for example, a superior vena cava, the annular motion values do not necessarily reflect the motion from that reference point. Therefore, the motion parameters chosen for this experiment may be deemed sufficient for preclinical operation on the tricuspid valve. Additional focus was placed on simulating the ability of the device 3302 to comply with the tricuspid valve motion rather than pulsatile flow because pressure and flow rate inside the right atrium of a heart are low compared to a left side of the heart. Mean pressures in the right atrium are approximately 8 mmHg.

[0203] FIG.34 illustrates example findings of time to complete a successful puncture using the experimental setup of FIG.32 in static and beating tricuspid valve annular tissue. In the in vitro tests, the median time for the static case was 54.3 s, and the median time for the motile case was 56.2 s. In the ex vivo tests, the median time for the static case was 83.0 s, and the median time for the motile case was 84.0 s. Values for a 25th percentile, a 75th percentile, and range extremes for time to completion are also shown. From the static in vitro test to the beating ex vivo test, the median times to completion increased, mirroring increasing difficulty of each task.

[0204] FIGS.35A-D illustrates an example soft manipulator 3516 in vertical (FIGS.35A, 35B) and angled deployment (FIGS.35C, 35D) configurations bending due to beating motions. A device 3502 including the soft manipulator 3516 and a stabilization mechanism (not shown but similar with respect to the stabilization mechanism 114, 214, 314) is illustrated. The stabilization mechanism is deployed in a lumen 3534, for example, an ex vivo porcine superior vena cava. The soft manipulator 3516 is actuated and in constant contact with an acrylic target. FIGS.35A and 35B illustrates the soft manipulator 3516 actuated in an extension state under normal (top left) and beating (top right) conditions. FIGS.35C and 35D illustrate the soft manipulator 3516 actuated in a bent state under normal (bottom left) and beating (bottom right) conditions, wherein the acrylic target is positioned at a 45° angle from a longitudinal axis of the soft manipulator 3516.

[0205] FIG.36 illustrates example measurements of contact force transmission over time in a beating environment using the experimental setup of FIG.32. Force transmission measurements are acquired for the soft manipulator 3516 over time for both the extension state 3562-1 and the bent state 3562-2 of FIGS.35A-D. The contact force is measured to be between 0.22 and 0.52 N after 70 s in a 45° bent state. The contact force is measured to be between 0.43 and 0.80 N after 70 s in extension state. For both target locations, the soft manipulator 3516 successfully applied - 38 - 4088749.v26200.2002002 (BU-2023-001) over half a newton of force at least once during each cycle and never lost contact with the acrylic contact until the end of the experiment.

[0206] FIG.41 illustrates an example embodiment of a device 4102 for performing stabilized endoluminal procedures with modifications for performing annuloplasty procedures. The device 4102, similar to the device 102, 202, 302, comprises a stabilization mechanism 4114 and a soft manipulator 4116. A tip of the soft manipulator 4116 is modified to deliver an anchor 4192. The anchor may comprise a threaded head, a sharpened coil, and a pressure fit tube. The soft manipulator 4116 includes a tool guide 4136 configured to provide a threaded interface to couple instruments to a tip of the soft manipulator 4116.The anchor 4192 is configured to be delivered by a driver 4191 that can be operated remotely by an operator. EXAMPLE 2 – EX-VIVO CORONARY SINUS CANNULATION IN A STATIC HEART

[0207] In a pacemaker lead placement procedure in the coronary sinus, an operator must locate the coronary sinus using a combination of guiding catheters and wires, as well as X-ray fluoroscopic imaging for visual feedback. A common method for coronary sinus cannulation utilizes a telescoping-support catheters technique, wherein a 9 Fr guiding sheath locates a coronary sinus ostium, an angiography catheter is used for contrast-aided verification, and a guide wire assists with proper lead positioning. Telescoping-support catheters fit concentrically within one another so that successively smaller tools can translate and rotate with respect to the larger sheath. However, locating the coronary sinus using the telescoping-support catheters technique can be time- and radiation-intensive due to navigational challenges and physical barriers to the coronary sinus ostium. These physical barriers include an obtrusive Thebesian valve and variable location of the coronary sinus itself from patient to patient. As a result, stiff and pre-shaped guiding sheaths may struggle to follow trajectories needed to cannulate the coronary sinus.

[0208] FIGS.37A-C illustrate an example coronary sinus pacemaker lead placement procedure using a device for performing a stabilized endoluminal procedure. As illustrated in FIG.37A, a device 3702a similar to the device 102, 202, 303 comprises a soft manipulator 3716a. The device 3702a may be navigated to an anatomical location, for example, the right atrium 3735a of a heart. The right atrium 3735a includes a Thebesian valve 3788a and a coronary sinus 3790a. FIG.37B illustrates a device 3702b similar to the device 3702a comprising a stabilization mechanism 3714 in a deployed state, stabilizing a catheter (not shown) of the device 3702b in a body lumen, for example, a superior vena cava 3734. The device 3702b further comprises a soft manipulator 3716b. The soft manipulator 3716b is actuated to position a - 39 - 4088749.v26200.2002002 (BU-2023-001) tip of the soft manipulator 3716b is in proximity to a Thebesian valve 3788b and a coronary sinus 3790b of the right atrium 3735b of a heart. FIG.37C illustrates a device 3702c similar to the device 3702c. The device 3702c further includes a soft manipulator 3716c. The soft manipulator 3716c is actuated to position a tip of the soft manipulator 3716c is in proximity to a Thebesian valve 3788c and a coronary sinus 3790c of the right atrium 3735c of a heart. An endoluminal device 3738 may be passed through the soft manipulator into the coronary sinus 3790c to perform an endoluminal procedure, specifically, the coronary sinus pacemaker lead placement procedure.

[0209] FIG.38A illustrates an example explanted porcine heart for a coronary sinus lead placement procedure. For the experiment, five users deployed a device similar to the device 102, 202, 302 and cannulated the coronary sinus, as shown in FIGS.37A-C. Each user performed five trials. FIG.38B illustrates example results of procedure times for performing a coronary sinus lead placement procedure. For each user, a median, 25th percentile value, 75th percentile value, and range are presented. The overall mean time to complete the procedure across users after discarding each user’s slowest and fastest times was 68 ± 37 s. In every test case, each user was able to approach procedural times on par with a control trial wherein an experienced clinician performed the task with an off-the-shelf curved-tip catheter. EXAMPLE 3 – CORONARY SINUS CANNULATION IN AN EX-VIVO HYBRID BIOROBOTIC BEATING HEART

[0210] In a separate experiment, a device similar to the device 102, 202, 302 was evaluated in an ex vivo hybrid biorobotic beating heart. The biorobotic beating heart was created using chemical fixation followed by a decellularization process to maintain cardiac anatomy and tissue properties of explanted porcine hearts. The native myocardium of the explanted porcine hearts was replaced by soft robotic myocardium to replicate function on a benchtop. The hearts were integrated in a mock flow loop, promoting physiologic hemodynamics and tissue mechanics. The hybrid biorobotic heart has been previously described, for example, in articles by Park et al., entitled “Biorobotic hybrid heart as a benchtop cardiac mitral valve simulator,” published in Device, Volume 2, Issue 1, 100217, on January 19, 2024, and by Singh et al., entitled "Hemodynamic evaluation of biomaterial-based surgery for Tetralogy of Fallot using a biorobotic heart, in silico, and ovine models”, published in Science Translational Medicine, Vol 16, Issue 755 on July 10, 2024.

[0211] FIG.38C illustrates example results from an experiment measuring intraluminal pressures in a biorobotic beating heart with and without a device for performing stabilized - 40 - 4088749.v26200.2002002 (BU-2023-001) endoluminal procedures. Plotted are intraluminal pressures in the right atrium 3852-1, right ventricle 3852-2, and pulmonary artery 3852-3 over five heartbeats without the device, i.e., a baseline case, and five heartbeats with the device deployed inside the biorobotic heart, i.e., a device case. No appreciable change is recorded from the baseline case to the device case. This shows the robot does not affect physiological blood flow while deployed. EXAMPLE 4 – IN-VIVO CORONARY SINUS LEAD PLACEMENT AND BIVENTRICULAR PACING IN A SWINE MODEL

[0212] A separate experiment using a device, for example, a robot, to perform a stabilized endoluminal procedure to achieve biventricular pacing of a heart in a live porcine model was performed. A procedure similar to that shown in FIGS.37A-C is performed under x-ray fluoroscopic guidance. Upon reaching a general location of the coronary sinus, a guidewire was inserted through a soft manipulator to achieve initial cannulation. Once the guidewire was inserted into the coronary sinus, an angiography guiding catheter was passed over the guidewire for contrast dye injection. The device gives an operator, for example, an interventionalist, the stability to maintain a given position while probing a location with the guide wire. If the initial location is incorrect, i.e., the guidewire does not successfully enter the coronary sinus, the robot can make fine adjustments in the same general area. This contrasts with conventional catheters that lack a stable base. If successful, the contrast dye would highlight the native shape of the coronary sinus under fluoroscopy.

[0213] FIGS.39A-C illustrate an example in vivo coronary sinus lead placement procedure viewed under x-ray fluoroscopy. FIG.39A illustrates a device, similar to the device 102, 202, 302, positioned within a heart of a pig. FIG.39B illustrates cannulation of a coronary sinus with a guidewire. FIG.39C illustrates visual feedback under x-ray fluoroscopy with contrast verifying cannulation of the coronary sinus.

[0214] FIG.40 illustrates example findings of a biventricular pacing experiment in an in vivo porcine model. Following successful cannulation of a coronary sinus, similar to the coronary sinus lead placement procedure illustrated in FIGS.39A-C, a pacing lead was inserted through the device to simulate biventricular pacing. The heart rate increased from 90-100 beats per minute (bpm) to 140-150 bpm, indicating successful lead placement and electrical capture at the selected pacing rate.

[0215] FIGS.42A-F illustrate example metrics for an experiment comparing coronary artery lead placement using a device for performing a stabilized endoluminal procedure and a conventional catheter. The device may be similar to the device 102, 202, 302 and may be a robot, - 41 - 4088749.v26200.2002002 (BU-2023-001) for example, a soft robot. Soft balloon actuators of the device, which may be similar to the soft multiple actuators 118, 218, 318, may be actuated with fluids including saline or a contrast agent visible under fluoroscopy. The results are divided into initial cannulation attempts (FIG.42A-C) and subsequent cannulation attempts (FIGS.42D-F). During the initial attempts, operators, for example, clinicians, did not know where the coronary sinus was located, as is the case in real clinical intervention. Because of this, exploration and probing constituted a large portion of the overall procedure. At least 100 guidewire probes were required during a 60-minute control trial as shown in FIGS.42A and 42B and over thirty minutes of x-ray fluoroscopy were required as shown in FIG.42C. These control metrics are consistent with literature, which states that coronary sinus cannulations can last up to several hours, with around thirty minutes of fluoroscopy exposure. Trials with the robot, however, showed a marked decrease across all metrics. When actuated with just saline, the robot required an average of 16 guide wire probes (FIG.42A), during trials that lasted just 22 minutes and eight minutes of fluoroscopy exposure (FIGS.42B and 42C). Contrast dye actuation proved especially beneficial, requiring only four wire probe attempts before reaching the coronary sinus, with the total procedure taking just over eight minutes, and 3.5 minutes of X-ray exposure FIGS.42A-C. In this case, the robot enabled a nearly ten-fold decrease in the duration of harmful X-ray use, with improvements of a similar magnitude in the other two metrics.

[0216] The subsequent attempts constituted trials performed after an initial attempt, without removing the robot or catheters from a heart. Importantly, this gave the clinicians a general sense of the location of the coronary sinus. Despite this prior knowledge, the control trials still required between 20 and 32 guidewire probe attempts, with an exception of one true statistical outlier trial that required three (FIG.42D). This is compared with three or fewer probes for all robot trials, whether actuated with saline or contrast. Overall duration of the procedure and fluoroscopy, however, became equalized across all subsequent attempts, regardless of whether they were performed by the robot or standard catheters. The control trials lasted a total of five minutes on average, compared with 8.5 minutes for the robot with saline actuation, and under four minutes for the robot with contrast actuation (FIG.42E). The control trials required approximately three minutes of fluoroscopy exposure on average, while the robot with saline actuation required approximately four minutes, and the robot with contrast actuation approximately two minutes on average (FIG.42F). In general, the dilute contrast dye actuation allowed subsequent attempt trials to be performed in the least amount of time and with shortest duration of fluoroscopy exposure (FIGS.42E-F), but not by an appreciable amount. - 42 - 4088749.v26200.2002002 (BU-2023-001)

[0217] Separate from the clinical exemplifications, a device, similar to the device 102, 202, 302 was demonstrated during insertion and removal from a heart to fit through a 24-Fr introducer sheath, for example, introducer sheath 305. To fit, a soft manipulator must be radially collapsed before insertion and before removal through the introducer sheath. Ultimately, the device could be collapsed to a diameter of 8 mm for percutaneous cardiac access. Upon reaching the right atrium, a stabilization mechanism can be deployed to shape-lock the device against a vessel, e.g., a superior vena cava, while the soft manipulator expanded its nominal diameter, e.g., to a nominal diameter of 15 mm, to exploit a larger intracardiac workspace. Radial collapse could be performed remotely, with the soft manipulator inside of the heart, to allow for removal through the same 24 Fr introducer sheath. After removal, the device remained intact and functional.

[0218] The teachings of all patents, published applications, and references cited herein are incorporated by reference in their entirety.

[0219] While example embodiments have been particularly shown and described, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the embodiments encompassed by the appended claims. - 43 - 4088749.v2

Claims

6200.2002002 (BU-2023-001) CLAIMS What is claimed is:

1. A device for performing a stabilized endoluminal procedure, the device comprising: a catheter including a proximal end and a distal end, the catheter defining a working channel and configured to carry multiple fluidic lines; a stabilization mechanism coupled to the catheter and configured to change between an undeployed state and a deployed state, the stabilization mechanism configured to expand in the deployed state to stabilize the catheter in a lumen; a soft manipulator disposed distal to the stabilization mechanism and including multiple actuators, the multiple actuators defining respective inflatable chambers fluidically coupled to the corresponding multiple fluidic lines, the multiple actuators configured to inflate and to deflate, wherein the soft manipulator is configured to expand, to collapse, or to bend based on inflating and deflating of the multiple actuators, the soft manipulator further configured to define a guided working channel in communication with the working channel; and a hub disposed at the proximal end of the catheter, the hub in coupled arrangement with a stabilization actuator configured to deploy the stabilization mechanism to stabilize the catheter in the lumen, the hub configured for passage of the multiple fluidic lines to couple fluidically to a fluidic actuator system, the hub defining a port continuous with the working channel, wherein the port is configured to enable passage of an interventional device through the catheter to perform the endoluminal procedure.

2. The device of claim 1, wherein the stabilization mechanism includes a fixed end coupled statically to the catheter, a moveable end configured to move relative to the fixed end, and multiple beams extending between the fixed end and the moveable end, wherein the moveable end is configured to slide towards the fixed end in the deployed state causing the multiple beams to bend at least in a radial direction away from the catheter.

3. The device of claim 2, wherein the stabilization mechanism is mechanically coupled to the stabilization actuator using at least one cable, wherein the catheter is further configured to carry the at least one cable and the stabilization actuator is further configured to deploy the stabilization mechanism by applying a tension to the cable. - 44 - 4088749.v26200.2002002 (BU-2023-001) 4. The device of claim 2, wherein the stabilization mechanism includes a rigid backbone having a length at least as long as a length of the stabilization mechanism in the undeployed state.

5. The device of claim 2, wherein the stabilization mechanism includes a first stabilization element and at least one second stabilization element.

6. The device of claim 5, wherein the first stabilization element and the at least one second stabilization element are configured to deploy individually or to deploy collectively.

7. The device of claim 2, wherein a beam of the multiple beams includes a single panel or a plurality of panels.

8. The device of claim 2, wherein the multiple beams of the stabilization mechanism are constructed using nitinol or another alloy or polymer.

9. The device of claim 2, wherein a beam of the multiple beams includes a wider central section and narrower side sections, the wider central section increasing contact area between the beam and the blood vessel, increasing resistance to bending of the beam, or both.

10. The device of claim 1, further comprising a tool guide disposed at a face of the soft manipulator, the tool guide configured to guide delivery of the interventional device by promoting orthogonality of the interventional device passing through the guided working channel with respect to the face of the manipulator.

11. The device of claim 1, wherein an actuator of the multiple actuators is a balloon actuator.

12. The device of claim 11, wherein each balloon actuator is a stacked ballon actuator and defines a continuous series of inflatable chambers, a chamber of the continuous series of inflatable chambers having a concave cross-sectional shape.

13. The device of claim 1, wherein the guided working channel of the soft manipulator is of size 1 French or greater and preferably of size 7.5 French or greater, the soft manipulator further configured to bend more than 70 degrees and preferably more than 200 degrees with respect to a base of the soft manipulator while maintaining the size of the guided working channel.

14. The device of claim 1, wherein the soft manipulator further includes a collapsible tubing in coupled arrangement with the multiple actuators and configured to define the guided working channel.

15. The device of claim 1, further comprising the fluidic lines. - 45 - 4088749.v26200.2002002 (BU-2023-001) 16. The device of claim 1, further comprising a sensor or a marker, the sensor configured to detect a property of the device or an environment therein, the marker configured to enable the sensing of an attribute of the device.

17. The device of claim 16, wherein the device comprises the sensor, the sensor being a force sensor disposed at a tip of the soft manipulator, the force sensor configured to detect forces applied to the tip of the soft manipulator.

18. The device of claim 17, further comprising a conductive trace disposed on the outer surface of or embedded in the multiple actuators, the conductive trace configured to couple communicatively the force sensor to a processor.

19. The device of claim 16, wherein the device comprises the marker, the marker being a magnetic marker disposed on the soft manipulator and configured to enable sensing of a position of the soft manipulator.

20. The device of claim 1, further comprising the interventional device.

21. The device of claim 20, wherein the interventional device includes an annuloplasty device or a conductive lead.

22. The device of claim 1, wherein the stabilization mechanism in the undeployed state and the soft manipulator in a collapsed state are configured to pass through an introducer sheath of diameter 1 centimeter or smaller, further wherein the stabilization mechanism is configured to undergo at least a two-fold expansion in a fully deployed state.

23. The device of claim 1, wherein the endoluminal procedure is a beating heart procedure.

24. The device of claim 1, wherein the hub further defines a flush port, the flush port in communication with the working channel, the flush port configured to enable delivery of a lubricant to the working channel.

25. A system for performing a stabilized endoluminal procedure, the system comprising: the device of any one of claims 1-24; an actuation system including multiple fluidic devices, the multiple fluidic devices coupled fluidically with the respective multiple fluidic lines, the multiple fluidic devices configured to inflate or deflate the multiple respective inflatable chambers of the soft manipulator by injecting or extracting a fluid.

26. The system of claim 25, wherein a fluidic device of the multiple fluidic devices is or includes a syringe.

27. The system of claim 25, further comprising: a processor, the processor communicatively coupled with: - 46 - 4088749.v26200.2002002 (BU-2023-001) multiple stepper motors, the multiple stepper motors in coupled arrangement with the respective multiple fluidic devices of the actuation system, the multiple stepper motors configured to control injecting or extracting of the fluid by the respective multiple fluidic devices; and a controller configured to receive inputs from an operator; wherein the processor is configured to operate the multiple stepper motors based on the inputs received from the operator on the controller.

28. The system of claim 27, further comprising a sensor disposed on the device, wherein the processor is communicatively coupled to the sensor and to sense a property of the device or an environment therein using the sensor.

29. The system of claim 27, further comprising a magnetic marker disposed on the soft manipulator and a magnetic sensor, the magnetic sensor configured to sense a position of the magnetic marker, wherein the processor is communicatively coupled with the magnetic sensor and configured to detect a position of the magnetic marker on the soft manipulator.

30. A method for performing a stabilized endoluminal procedure, the method comprising: navigating a catheter through a lumen; stabilizing the catheter in the lumen by changing a stabilization mechanism coupled to the catheter into a deployed state, the stabilization mechanism configured to expand in at least a radial direction in a deployed state; and actuating a soft manipulator disposed distal to the stabilizing mechanism by selectively inflating or deflating multiple actuators of the soft manipulator, wherein the actuating includes extending, collapsing, or bending the soft manipulator, the soft manipulator configured to guide an interventional device to an anatomical location to perform the endoluminal procedure.

31. The method of claim 30, further comprising sensing a property of the soft manipulator, the stabilization mechanism, the catheter, or a combination thereof.

32. The method of claim 30, further comprising detecting a position of the soft manipulator.

33. The method of any one of claims 30-32, further comprising changing the stabilization mechanism into an undeployed state from the deployed state to enable the removal of the catheter from the lumen.

34. The method of any one of claims 30-32, wherein the stabilized endoluminal procedure is a cardiovascular procedure and the lumen is a blood vessel. - 47 - 4088749.v2

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