Enteroscopic robots and related methods

Abstract

System configured to facilitate locomotion at a location internal to a subject are generally presented. In some embodiments, the present invention generally relates to enteroscopic robots and related methods, such as bioinspired soft enteroscopic robots for facilitating locomotion, steering, and intervention in the small intestine. In some embodiments, the system comprises a flexible linear actuator, a first expandable actuator operably linked to the first end of the flexible linear actuator, and a second expandable actuator operably linked to the second end of the flexible linear actuator. In some embodiments, the system enables the delivery of one or more tools, one or more pharmaceutical agents, and / or one or more electronic components to a location internal to the subject (e.g., the small intestine).

Description

[0001] ENTEROSCOPIC ROBOTS AND RELATED METHODS RELATED APPLICATIONS

[0002] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application Serial No. 63 / 710,745, filed October 23, 2024, and entitled “ENTEROSCOPIC ROBOTS AND RELATED METHODS,” which is incorporated herein by reference in its entirety for all purposes.

[0003] FIELD

[0004] The present invention generally relates to soft enteroscopic robots and related methods, such as bioinspired soft enteroscopic robots for facilitating locomotion, steering, and intervention in the small intestine.

[0005] BACKGROUND

[0006] Diagnosing and treating small intestinal disorders such as bleeding, inflammatory bowel disease, and tumors presents significant challenges due to the difficulty of accessing this anatomical compartment.

[0007] Accordingly, improved systems, articles and methods are needed.

[0008] SUMMARY

[0009] The present invention generally relates to soft enteroscopic robots and related methods.

[0010] In one aspect, systems are provided (e.g., systems configured to facilitate locomotion at a location internal to a subject). In some embodiments, the system comprises a flexible linear actuator having a first end and a second end, a first expandable actuator operably linked to the first end of the flexible linear actuator, a first sleeve adjacent the first expandable actuator, the first sleeve comprising a first patterned surface, a second expandable actuator operably linked to the second end of the flexible linear actuator, and a second sleeve adjacent the second expandable actuator, the second sleeve comprising a second patterned surface.

[0011] In some embodiments, the system comprises a flexible linear actuator having a first end and a second end, a first expandable actuator operably linked to the first end of the flexible linear actuator, a second expandable actuator operably linked to the second end of the flexible linear actuator, and at least one channel extending through the flexible linear actuator, the first expandable actuator, and the second expandable actuator.

[0012] In another aspect, methods are provided. In some embodiments, the method comprises administering to a subject, endoscopically, an enteroscopic robot, the enteroscopic robot comprising a flexible linear actuator having a first end and a second end, a first expandable actuator operably linked to the first end of the flexible linear actuator, a first sleeve adjacent the first expandable actuator, the first sleeve comprising a first patterned surface, a second expandable actuator operably linked to the second end of the flexible linear actuator, and a second sleeve adjacent the second expandable actuator, the second sleeve comprising a second patterned surface and locomoting the enteroscopic robot, wherein locomoting comprises performing one or more of the following steps: expanding the first expandable actuator, extending the flexible linear actuator, expanding the second expandable actuator, deflating the first expandable actuator, shrinking the flexible linear actuator, and deflating the second expandable actuator.

[0013] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document Incorporated by reference include conflicting and / or inconsistent disclosure, the present specification shall control.

[0014] BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. In the figures:

[0016] FIG. 1 is a schematic of a robot system design, according to one set of embodiments. A) Various intestinal health conditions and theranostic opportunities. B) Inspiration by snake's adaptive movements: (i) rectilinear locomotion, (ii) bending, and (iii) scales oriented to increase friction. C) Schematic illustration, exploded view, and D) Optical photo of (i) the control box with (ii) a wireless joystick controller, and (iii) bioinspired soft enteroscopic robot (BIOSENTER). Lo = 95 mm, Do = 14 mm. The scale bar is 10mm. E) Snapshots of the fiber-reinforced robotic body with both elongation and steering capability. F) Kirigami sleeves before and after radial expansion at 50 kPa. The scale bar is 15mm. G) Photo of BIOSENTER accessories, including drug delivery tubing, air tubing, a camera, LED, and an alligator forceps for imaging, localized drug delivery, and tissue biopsy. The scale bar is 7.5 mm. Ventral-Dorsal (VD) X-ray showing a representative swine post-insertion of the device, marked with X-ray opaque conductive ink on the Kirigami sleeves. The Kirigami sleeves are expanded in this snapshot. H) Snapshots of forward robotic locomotion in an intestinal phantom, showing the sequence of (i) robot entering the small intestine (SI), (ii) tail unit inflation for anchoring, (iii) body unit inflation for elongation, (v) head unit inflation for anchoring, (vi) deflation of both tail unit and body unit for forward crawling, (iv) tail unit inflation for anchoring again and head unit deflation.

[0017] FIG. 2 shows body unit characterization, according to one set of embodiments. A) Schematic of the robotic body with four independent inflatable chambers. Insets denote the characteristic Kevlar fiber angle and cross-sectional view, with gray zones denoting the four independent inflatable chambers. B) Photo of a 3D-printed robotic body with a four-chamber design, shown as the cross-sectional view. C) The four-chamber design achieves a 360° continuous planar access. Precise 45° discrete steps are achieved with isobaric chambers activation. D) The extension-pressure curve of the fiber-reinforced robotic body with all four chambers activated. Snapshots of fiber-reinforced robotic body under various air pressures. E) Bending-pressure curve of the fiber-reinforced robotic body with two adjacent chambers activated. Snapshots of the fiber-reinforced robotic body under various air pressures. Values in panels D and E represent the mean and the standard deviation (n = 3).

[0018] FIG. 3 shows anchoring unit characterization, according to one set of embodiments. A) Schematic illustration of an anchoring unit with an optimized Kirigami sleeve in the unidirectional triangle shape. The inset shows the balloon’s cross-sectional view. B) Kirigami sleeve fabrication using laser cutting and engraving. C) Top and side views of the anchoring unit under various air pressures. D) Numerical simulation of the anchoring unit's radial expansion under various air pressures. E) Relative diameter changes and popping angle of the anchoring unit under various air pressures. The insets show the schematic of the popping angle measurement and its corresponding simulation results. Values in panel E represent the mean and the standard deviation (n = 3-9). F) Force-time curve during the pulling test (i) and the average pulling force (ii) of the anchoring unit without the Kirigami sleeve (w / o Kirigami), with the Kirigami sleeve (w / o raster), and with both Kirigami sleeve and raster (w raster). The expansion diameters were equalized by adjusting the air pressure. Values in panel F(ii) represent the mean and the standard deviation (n = 5). G) Pulling force of the anchoring unit with the Kirigami sleeve and raster under various air pressures. Values in panel G represent the mean and the standard deviation (n = 6). H) Diameter change of the anchoring unit with the Kirigami sleeve to achieve a clinically acceptable friction force (~1.5 N). I) Diameter change of the anchoring unit without the Kirigami sleeve to achieve a clinically acceptable friction force (-1.5 N). Note: The data presented in panels F and G were collected from two individual pigs. The balloons presented in panels H and I were cast from silicone rubber (Double Elite 22; Zhermack SpA, Italy).

[0019] FIG. 4 shows spring characterization, according to one set of embodiments. A) A photo of the superelastic nitinol reinforcement spring. B) The inner hollow chambers (i) collapse or (ii) do not collapse when body unit actuators are pressurized without and with the spring inserted, respectively. C) The inner hollow chambers (i) collapse or (ii) do not collapse when anchoring unit actuators are pressurized without and with the spring inserted, respectively. D) Extension difference of body units under 180 kPa in three scenarios: without (w / o) the spring and cable, with (w) the spring and cable, and without the spring but with the cable. Values in panel D represent the mean and the standard deviation (n = 4). E) Bending difference of the body units with one chamber activated under 180 kPa in two scenarios: without (w / o) and with (w) the spring.

[0020] FIG. 5 shows control box design and performance characterization, according to one set of embodiments. A) A photo of the (i) control box, (ii) its architecture schematic, (iii) photos of the 2-layer PCB of the control box, and (iv) joystick controller PCB. B) Snapshots of achieving real-time steering of the body unit with the joystick controller’s knob. C) Snapshots of BIOSENTER aiming at targets placed 45° around a circle. The robot was deployed in a section of 20-mm tubing and the soft manipulator guided forceps through five 1-cm holes in a timed trial. D) Demonstration of BIOSENTER’ s steering and manipulation capabilities by grabbing an object randomly placed in front of the robot.

[0021] FIG. 6 shows motion analysis of an exemplary BIOSENTER robot, according to one set of embodiments. A) The schematic of the actuation sequences for forward locomotion. B) Locomotion through a straight path. C) Locomotion through an inclined path at 30°. D) Locomotion through a curved path. E) Robot’s locomotion inside a tube covered with SI tissue to mimic in vivo texture. F) Tissue push-and-pull maneuvers performed with and without the Kirigami sleeve on the robots. Values in panel F (vii) represent the mean and the standard deviation (n = 3). G) Tissue retrieval test on porcine intestinal models under four balloon conditions: (1) without (w / o) Kirigami, 0 kPa; (2) without (w / o) Kirigami, 15-20 kPa; (3) without (w / o) Kirigami, 45-50 kPa; (4) with (w) Kirigami, 45-50 kPa. H) Change in diameter of the in vivo small intestine before and after balloon inflation at approximately 45 kPa.

[0022] FIG. 7 shows in-vivo experiments, according to one set of embodiments. A) A schematic showing a pig being treated with the BIOSENTER either down the esophagus or up through the anus. B) An abdominal view of the robot moving inside the SI of a sedated animal. A ventral midline laparotomy was used to visualize the SI. C) X-ray images showing a representative device locomoted in the swine’s intestinal segments (i) before and (ii) after bending. D) Histological analysis of the tissue after BIOSENTER operation, showing no significant differences between control and treated tissues. E-G) Demonstrations of visualization, drug delivery, and biopsy in the SI, respectively. The snapshot of panel E was taken using the camera attached to the BIOSENTER. The snapshots of panels F and G were taken using the camera attached to the endoscope.

[0023] FIG. 8 shows an overview of an exemplary double-balloon enteroscopy (DBE) operation, according to one set of embodiments. 1) Endoscope inserted through the overtube.

[0024] 2) Endoscope balloon inflated. 3). Overtube advanced along the endoscope. Overtube balloon inflated. 4) Endoscope balloon deflated. 5) Endoscope advanced deeper into the intestine. 6) Overtube balloon inflated. 7) Overtube advanced along the endoscope. Overtube balloon inflated. 8) Endoscope-overtube pulled back to straighten path through intestine. 9) Endoscope balloon deflated. Endoscope advanced again. FIG. 9 shows a cross-sectional view of the BIOSENTER robot assembly with incremental 45° degrees of rotation of the cross-section plane, demonstrating the internal architecture and pneumatic channels, according to one set of embodiments.

[0025] FIG. 10 shows a photo of soft robots fabricated using 3D printing and injection molding, according to one set of embodiments.

[0026] FIG. 11 shows BIOSENTER fabrication using injection molding, according to one set of embodiments. A) Exploded view of BIOSENTER robot assembly. B) (i-iii) Fabrication process of the head anchoring unit using injection molding, (iv) Optical photo showing the 3D-printed injection mold. C) (i-iii) Fabrication process of the body unit using injection molding, (iv) Optical photo showing the 3D-printed injection mold. D) (i-iii) Fabrication process of the tail anchoring unit using injection molding, (iv) Optical photo showing the 3D-printed injection mold. E) Fabrication process of the End-Cap using injection molding, (iv) Optical photo showing the 3D-printed injection mold.

[0027] FIG. 12A shows an overview of injection molded robot assembly, according to one set of embodiments, (i) Assembling the head unit and body unit, (ii) Assembling the tail unit and body unit, (iii) Assembling the End-Cap and tail unit, (iv) Assembling the seal-cap onto the End-Cap for guiding silicone pipes.

[0028] FIG. 12B shows an overview of the accessory cap schematic and cross-section view, according to one set of embodiments.

[0029] FIG. 13 shows body unit characterization with two opposite chambers activated, according to one set of embodiments. Values in the left panel represent the mean and standard deviation (n = 3). Snapshots of the fiber-reinforced robotic body under various air pressures are shown on the right.

[0030] FIG. 14 shows body unit characterization with three adjacent chambers activated, according to one set of embodiments. Values in the left panel represent the mean and standard deviation (n = 3). Snapshots of the fiber-reinforced robotic body under various air pressures are shown on the right.

[0031] FIG. 15 shows body unit characterization with one chamber activated, according to one set of embodiments. Values in the left panel represent the mean and standard deviation (n = 3). Snapshots of the fiber-reinforced robotic body under various air pressures are shown on the right. FIG. 16 shows Kirigami sleeve details, according to one set of embodiments. A) Visual displaying the details of the Kirigami sheet, highlighting the overlap region and margin bands designed to create a robust Kirigami sleeve shell. B) The schematic shows a deflated anchoring unit and an approximation of the dimensions of the inflated unit where Do and Ho are the initial actuator diameter and height, respectively.

[0032] FIG. 17 shows Kirigami sleeve characterization, according to one set of embodiments. A) Schematic of the pull test setup showing an inflated balloon with the Kirigami sleeve on SI tissue. B) Comparison of the anchoring force for two different multi- directional Kirigami patterns with a unidirectional triangular pattern evaluated at 50 kPa actuator pressure. Values in the bottom panel represent the mean and standard deviation (n = 5). C) Comparison of the anchoring force for two alternating bi-directional Kirigami patterns with a unidirectional triangular pattern evaluated at 50 kPa actuator pressure. Values in the bottom panel represent the mean and standard deviation (n = 5).

[0033] FIG. 18 shows anchoring unit characterization with different Kirigami sheet thicknesses, according to one set of embodiments. Photos of the anchoring unit with various radial expansions and Kirigami sleeve pop-up angles for five different sheet thicknesses under the same balloon pressure (50 kPa).

[0034] FIG. 19 shows anchoring force characterization with different Kirigami sheet thicknesses, according to one set of embodiments, (i) Anchoring force-thickness curve.

[0035] Values represent the mean and standard deviation (n = 5). (ii) Anchoring forces were measured at the same level of radial expansion (D = 18.5 mm). The same expansion diameters were achieved with different balloon pressure levels.

[0036] FIG. 20 shows the performance of Kirigami sleeves, according to one set of embodiments. A) A photo showing that higher inflation pressure increases the risk of Kirigami hinge fracture. B) The anchoring forces for the Kirigami sleeves with different Kirigami pattern sizes are measured at the same level of radial expansion. Values in the bottom panel represent the mean and the standard deviation (n = 4-5).

[0037] FIG. 21 shows expansion diameters and friction force of the anchoring actuator, according to one set of embodiments. A) Force-time curves for balloons with (w) and without (w / o) the Kirigami sleeve. The bare balloon expanded five times more than the one with the Kirigami sleeve to provide the same force profile. B) The change in normalized diameter of bare balloons as a function of pressure. Values represent the mean and the standard deviation (n = 3). C) Visual representation of the change in balloon diameter at different pressure levels.

[0038] FIG. 22 shows the fabrication process of the superelastic nitinol reinforcement spring, according to one set of embodiments. A superelastic nitinol wire is tightly wound around a 5.8 mm aluminum jig and fixed at the two ends. The assembly is baked at 500°C in an oven (Carbolite Gero LHT) for 15 minutes and then quenched quickly. The fixture is inserted inside the hollow channel and the jig is released.

[0039] FIG. 23 shows a circuit schematic of the control board, according to one set of embodiments. A) The power management unit provides two high-power rails for the pumps (5-9V) and other components (6V), and two regulated power rails (5V and 3.3V) for signal and control components. B) The board is controlled with a Teensy 4.0 MCU, and the logic is transmitted through transistor arrays. A Bluetooth 5.0 module is used for wireless communication. C) Pumps are driven by motor drivers, each capable of sensing load current and setting output current limits. D) Output ports include JST connectors for the valves and pumps, and LED status indicators. E) Three pressure sensors are incorporated to measure the pressure of each chamber for a closed-loop locomotion control system.

[0040] FIG. 24 shows pressure performance characterization for the mini-pump at various drive currents, according to one set of embodiments.

[0041] FIG. 25 shows plumbing architecture and active inflation and deflation sequences, according to one set of embodiments. A) The connection schematic of the head / tail actuators with their respective pumps and three-way valves. B) The connection schematic of the body actuator with its respective pumps and three-way valves. Ix is the inflation valve, Dx is the deflation valve, and VBx is the control valve for each body actuator chamber. C) A separate pump is used for enteroscopic inflation purposes. All the M-ports on the three-way valves are connected to O-ports when off and 1 -ports when turned on. The green line highlights the pneumatic path for D) Active inflation of BIOSENTER actuators and E) active deflation of BIOSENTER actuators.

[0042] FIG. 26 shows an exemplary joystick controller design, according to one set of embodiments. A) Illustrates the joystick controller design schematic with a PCB sandwiched between two custom sheets. B) The schematic of the joystick PCB, consisting of a power management unit, a microcontroller, a Bluetooth module, and an array of switches and knobs.

[0043] FIG. 27 shows a control box housing, according to one set of embodiments. A) A schematic of the control box concept design was developed using Fusion 360. B) The box components were laser-cut from a 6 mm acrylic sheet with finger joints. C) The box was then assembled.

[0044] FIG. 28 shows a seal-Cap design and fabrication, according to one set of embodiments. A) Schematic of the Seal-Cap, highlighting its adhesive cavity. B) The Seal-Cap is attached to the End-Cap with Sil-Poxy adhesive, creating a sealed barrier for the pneumatic pipes. C) Cross-section of the tail anchoring unit, End-Cap, and Seal-Cap assembly at the back end of the robot. The sealing adhesive cavity is highlighted with the red arrow.

[0045] FIGs. 29A-29D show exemplary systems, according to one set of embodiments.

[0046] FIG. 30 shows push-assisted locomotion of a BIOSENTER robot traversing in vivo porcine small intestine tissue, according to one set of embodiments. The dashed box highlights the robot during push-assisted locomotion, while the dashed line represents the centerline of the small intestine.

[0047] FIG. 31 shows real-time force data recorded during a 3-meter ex vivo intestinal tissue push-pull test, according to one set of embodiments.

[0048] FIG. 32 shows friction force measurements between balloon devices and intestinal tissue across different lumen diameters, according to one set of embodiments. A) Relative friction force between fully expanded kirigami balloons (~50 kPa) and intestinal tissue segments with lumen diameters ranging from 13 to 17 mm. B) Relative friction force between non-kirigami balloons (~30 kPa) and intestinal tissue across the same diameter range. Values represent mean measurements (n = 3).

[0049] DETAILED DESCRIPTION

[0050] System configured to facilitate locomotion at a location internal to a subject are generally presented. In some embodiments, the present invention generally relates to enteroscopic robots and related methods, such as bioinspired soft enteroscopic robots for facilitating locomotion, steering, and intervention in the small intestine. In some embodiments, the system comprises a flexible linear actuator, a first expandable actuator operably linked to the first end of the flexible linear actuator, and a second expandable actuator operably linked to the second end of the flexible linear actuator. In some embodiments, the system enables the delivery of one or more tools, one or more pharmaceutical agents, and / or one or more electronic components to a location internal to the subject (e.g., the small intestine).

[0051] Advantageously, the systems and methods described herein may be useful for treatment of gastrointestinal diseases such as bleeding, ulcers, cancer, inflammatory bowel diseases (e.g., Crohn’s disease, ulcerative colitis), amongst others. Flexible enteroscopy systems, such as push, double-balloon, single-balloon, and spiral enteroscopes, have been developed for diagnostics and therapeutics (i.e., theranostics) in the small intestine. Among these, the double-balloon enteroscope (DBE) is generally the only non-surgical tool reported for examining the entire small intestine either down the esophagus or up through the anus, using sequences of balloon inflation and deflation along with push-and-pull maneuvers. Despite eliminating the need for abdominal surgery, the DBE procedure may cause complications including tissue overdistention, intestinal bleeding, and bowel perforation, mainly due to the device's rigidity and limited maneuverability. Additionally, DBE procedures often result in incompleteness due to slippage, a consequence of pressure-limited latex expansion balloons designed with smooth surface finish. The need for extensive training also hinders the practicality of DBE for routine use, as the operational complexity prolongs the procedure times to over 90 minutes.

[0052] Advantageously, the systems and methods described herein, in some embodiments, overcome the above-noted limitations of traditional methods by providing, for example, shorter procedure times, reduced slippage, significantly reduced risk of perforation, and / or easier user operation, amongst other benefits. In some embodiments, the systems and methods described herein are designed to significantly reduce and / or eliminate the risk of slippage of the device as it locomotes along the small intestine of a subject.

[0053] Advantageously, the systems and methods described herein may be used in conjunction with one or more additional components including one or more of a camera component, a light component, a drug delivery component, a biopsy component, a forceps component, and a fluidic component. In some embodiments, the systems and methods described herein are useful for diagnostic and / or therapeutic purposes such as imaging, drug delivery, and / or biopsy procedures at a location internal to a subject.

[0054] In some embodiments, the systems described herein are administered to a subject (e.g., surgically, endoscopically, orally). In certain embodiments, the system may be administered surgically (e.g., implanted), orally (e.g., swallowed, endoscopically), rectally (e.g., endoscopically), vaginally, nasally, or uretherally. In someone embodiments, upon reaching a location internal to the subject (e.g., a portion of the gastrointestinal tract such as the small intestine), the system may be operated such that it transits the location internal to the subject.

[0055] A “subject” refers to any animal such as a mammal (e.g., a human). Non-limiting examples of subjects include a human, a non-human primate, a cow, a horse, a pig, a sheep, a goat, a dog, a cat or a rodent such as a mouse, a rat, a hamster, a bird, a fish, or a guinea pig. Generally, the invention is directed toward use with humans. In some embodiments, a subject may demonstrate health benefits, e.g., upon administration of the systems described herein.

[0056] In some embodiments, the location internally of the subject is the colon, the duodenum, the ileum, the jejunum, the stomach, the small intestine, the large intestine, or the esophagus. In certain embodiments, the location internally of the subject is in the buccal space, in the venous system (e.g., an artery), in the respiratory system (e.g., lung), in the renal system, in the urinary system, or in the gastrointestinal system. In an exemplary set of embodiments, the location internal to the subject is the small intestine of the subject. In another exemplary set of embodiments, the location internal to the subject is the colon of the subject.

[0057] In some embodiments, the flexible linear actuator comprises a spring. In some embodiments, the spring may be a compression spring, an extension spring, or a torsion spring. Other types of springs are also possible. The spring may wrap around the outside of the flexible linear actuator. The spring may be located inside the flexible linear actuator. In some embodiments, the spring is embedded in at least a portion of the flexible linear actuator.

[0058] In certain embodiments, the location internal to the subject is the small intestine. In some embodiments, the system is equipped with hardware to conduct a tissue biopsy, for example, to analyze a polyp or to diagnose intestinal cancer. In some embodiments, the system is equipped with hardware to conduct localized treatment of, e.g., inflammatory bowel disease (IBD) or an ulcer. In some embodiments, the system is equipped with hardware to conduct imaging of, e.g., bleeding, or versatile symptoms.

[0059] In some embodiments, the locomotion at the location internal to the subject may include rectilinear motion, bending, and / or expansion of a patterned surface oriented to increase friction.

[0060] In some embodiments, the system is configured to facilitate locomotion at a location internal to the subject may be supplemented by a control box and a wireless controller (e.g., a wireless joystick controller) that controls the configuration of the system. For example, the wireless controller may be operated to do at least one of the following: expand the first expandable actuator; extend the flexible linear actuator; expand the second expandable actuator; deflate the first expandable actuator; shrink the flexible linear actuator; and deflate the second expandable actuator.

[0061] In some embodiments, the system has a suitable length so as to facilitate locomotion at a location internal to the subject. For example, in some embodiments, the system is greater than or equal to 30 mm, greater than or equal to 40 mm, greater than or equal to 50 mm, greater than or equal to 60 mm, or greater than or equal to 70 mm long. In some embodiments, the system is less than or equal to 200 mm, less than or equal to 150 mm, less than or equal to 100 mm, or less than or equal to 95 mm long. Combinations of the abovereferenced ranges are also possible (e.g., greater than or equal to 30 mm and less than or equal to 200 mm long, greater than or equal to 40 mm and less than or equal to 150 mm). Other ranges are also possible. In certain embodiments, the system is 95 mm long.

[0062] In some embodiments, the system has a suitable diameter so as to facilitate locomotion at a location internal to the subject, and optionally a diameter large enough to accommodate a functional component inside the system. For example, in some embodiments, the system has a diameter of greater than or equal to 5 mm, greater than or equal to 6 mm, greater than or equal to 7 mm, greater than or equal to 8 mm, greater than or equal to 9 mm, or greater than or equal to 10 mm. In some embodiments, the system has a diameter of less than or equal to 20 mm, less than or equal to 19 mm, less than or equal to 18 mm, less than or equal to 17 mm, less than or equal to 16 mm, less than or equal to 15 mm, less than or equal to 14 mm, less than or equal to 13 mm, less than or equal to 12 mm, or less than or equal to 11 mm. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 5 mm and less than or equal to 20 mm, greater than or equal to 6 mm and less than or equal to 19 mm). Other ranges are also possible. In certain embodiments, the system has a diameter of 14 mm.

[0063] In some embodiments, at least one channel extending through the flexible linear actuator, the first expandable actuator, and the second expandable actuator contains a spring. The spring may be a nitinol spring. The spring may have a diameter suitable to be contained in the channel. For example, in some embodiments, the spring has a diameter of greater than or equal to 1 mm, greater than or equal to 2 mm, or greater than or equal to 3 mm. In some embodiments, the spring has a diameter of less than or equal to 6 mm, less than or equal to 5 mm, or less than or equal to 4 mm. Combinations of the above -referenced ranges are also possible (e.g., greater than or equal to 1 mm and less than or equal to 6 mm, greater than or equal to 2 mm and less than or equal to 5 mm). Other ranges are also possible.

[0064] In some embodiments, the flexible linear actuator is wrapped in a fiber mesh. In certain embodiments, the fibers comprise Kevlar. In some embodiments, the fibers comprise other aramid fibers (e.g., Twaron, Technora, Nomex) and / or ultra-high-molecular-weight polyethylene (UHMWPE) fibers (e.g., Dyneema, Spectra). In some embodiments, the fibers are disposed on an internal surface of the flexible linear actuator. In some embodiments, the fibers are disposed on an external surface of the flexible linear actuator.

[0065] In some embodiments, the first sleeve comprising a first patterned surface is a Kirigami sleeve. In some embodiments, the second sleeve comprising a second patterned surface is a Kirigami sleeve. A sleeve may be patterned using a technique such as origami, jianzhi, origami architecture, and kirie. In some embodiments, a patterned surface has a pattern comprising diamonds, rhombi, squares, rectangles, ovals, circles, and / or hexagons (e.g., FIG. 17B). Other patterns may also be used and those of ordinary skill in the art would be capable of selecting suitable patterns based upon the teachings of this specification.

[0066] In some embodiments, the system further comprises a cap operably linked to the second expandable actuator. The cap may serve as a barrier between the location internal to the subject and the at least one channel extending through the flexible linear actuator, the first expandable actuator, and the second expandable actuator. In some embodiments, the system further comprises a cap operably linked to the first expandable actuator. The cap may include one or more (e.g., 2, 3, 4, 5, 6, 7, 8, or more) channels.

[0067] In some embodiments, the system locomotes at a location internal to the subject by elongation and / or steering.

[0068] The first expandable actuator and / or the second expandable actuator may radially expand at a suitable applied pressure that is not so high as to cause damage to tissue internal to the subject. For example, an expandable actuator may radially expand at an applied pressure of less than or equal to 100 kPa, less than or equal to 90 kPa, less than or equal to 80 kPa, less than or equal to 70 kPa, less than or equal to 60 kPa. An expandable actuator may radially expand at an applied pressure of greater than or equal to 10 kPa, greater than or equal to 20 kPa, greater than or equal to 30 kPa, greater than or equal to 40 kPa, or greater than or equal to 50 kPa. Combinations of the above-referenced ranges are also possible (e.g., less than or equal to 100 kPa and greater than or equal to 10 kPa, less than or equal to 90 kPa and greater than or equal to 20 kPa). Other ranges are also possible. In certain embodiments, an expandable actuator may radially expand at an applied pressure of 50 kPa.

[0069] The at least one channel extending through the flexible linear actuator, the first expandable actuator, and the second expandable actuator may house drug delivery tubing for localized drug delivery, air tubing, a camera and a light (e.g., light-emitting diode) for imaging, and / or an alligator forceps for tissue biopsy. There may be a certain number of channels to accommodate some or all of these items. In some embodiments, the flexible linear actuator comprises one, two, three, four, five, six, seven, eight, or nine or more channels. In some embodiments, each channel may be used to facilitate a different tool (e.g., drug delivery, air tubing, camera, light, biopsy, or the like). In some embodiments, one or more channels may be large enough (e.g., in diameter) to facilitate two or more such tools.

[0070] A method for locomoting an enteroscopic robot, such as a system described herein, may comprise the following sequence: administering to a subject, endoscopically, the enteroscopic robot; expanding the first expandable actuator for anchoring; extending the flexible linear actuator; expanding the second expandable actuator for anchoring; deflating the first expandable actuator and then shrinking the flexible linear actuator for forward crawling; expanding the first expandable actuator for anchoring and deflating the second expandable actuator.

[0071] In some embodiments, the fibers surrounding the flexible linear actuator have a characteristic angle relative to the cross-section of the flexible linear actuator to facilitate expansion of the flexible linear actuator. For example, in some embodiments the fibers surrounding the flexible linear actuator have a characteristic angle relative to the crosssection of the flexible linear actuator of less than or equal to 30 degrees, less than or equal to 20 degrees, or less than or equal to 14 degrees. In some embodiments the fibers surrounding the flexible linear actuator have a characteristic angle relative to the cross-section of the flexible linear actuator of greater than or equal to 5 degrees or greater than or equal to 10 degrees. Combinations of the above -referenced ranges are also possible (e.g., less than or equal to 30 degrees and greater than or equal to 5 degrees, less than or equal to 20 degrees and greater than or equal to 10 degrees). Other ranges are also possible. In certain embodiments, the fibers surrounding the flexible linear actuator have a characteristic angle relative to the cross-section of the flexible linear actuator of 14 degrees.

[0072] In some embodiments, the flexible linear actuator has a plurality of independent inflatable chambers. In some embodiments, the flexible linear actuator has 2, 3, 4, or more independent inflatable chambers. Advantageously, each independent inflatable chamber may be independently actuated (e.g., via application of air pressure to the inflatable chamber) such that the flexible linear actuator may be actuated (e.g., stretched, compressed, bent, turned, or the like). In certain embodiments, the independent inflatable chambers run parallel to one another along the length of the flexible linear actuator. In certain embodiments, these chambers run parallel to the at least one channel extending through the flexible linear actuator, the first expandable actuator, and the second expandable actuator.

[0073] In certain embodiments, four independent inflatable chambers in the flexible linear actuator facilitate bending of the flexible linear actuator at precise 45-degree increments depending on which one (or two adjacent) of the four chambers are activated (see, e.g., FIG.

[0074] 2C).

[0075] In certain embodiments, activation of all four independent inflatable chambers in the flexible linear actuator causes linear lengthening of the flexible linear actuator, wherein the length increase of the flexible linear actuator varies depending on the applied air pressure in all four independent inflatable chambers (e.g., FIG. 2D). For example, the flexible linear actuator may be lengthened by applying greater than or equal to 10 kPa, greater than or equal to 20 kPa, greater than or equal to 30 kPa, greater than or equal to 40 kPa, greater than or equal to 80 kPa, or greater than or equal to 120 kPa in all four independent inflatable chambers. The flexible linear actuator may be lengthened by applying less than or equal to 250 kPa, less than or equal to 200 kPa, less than or equal to 180 kPa, or less than or equal to 160 kPa in all four independent inflatable chambers. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 10 kPa and less than or equal to 250 kPa, greater than or equal to 20 kPa and less than or equal to 200 kPa). Other ranges are also possible.

[0076] In certain embodiments, activation of all four independent inflatable chambers in the flexible linear actuator causes linear lengthening of the flexible linear actuator, wherein the length increase of the flexible linear actuator varies depending on the applied air pressure in all four independent inflatable chambers (e.g., FIG. 2D). For example, the flexible linear actuator may be lengthened by greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 20%, or greater than or equal to 30%. The flexible linear actuator may be lengthened by less than or equal to 50%, less than or equal to 45%, less than or equal to 40%, or less than or equal to 35%. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 5% and less than or equal to 50%, greater than or equal to 10% and less than or equal to 45%). Other ranges are also possible.

[0077] In certain embodiments, activation of two adjacent chambers of the four independent inflatable chambers in the flexible linear actuator causes bending of the flexible linear actuator, wherein the bending angle of the flexible linear actuator varies depending on the applied air pressure in both independent inflatable chambers (e.g., FIG. 2E). For example, the flexible linear actuator may be bent by applying greater than or equal to 10 kPa, greater than or equal to 20 kPa, greater than or equal to 30 kPa, greater than or equal to 40 kPa, greater than or equal to 80 kPa, or greater than or equal to 120 kPa in two adjacent independent inflatable chambers. The flexible linear actuator may be bent by applying less than or equal to 250 kPa, less than or equal to 200 kPa, less than or equal to 180 kPa, or less than or equal to 160 kPa in two adjacent independent inflatable chambers. Combinations of the abovereferenced ranges are also possible (e.g., greater than or equal to 10 kPa and less than or equal to 250 kPa, greater than or equal to 20 kPa and less than or equal to 200 kPa). Other ranges are also possible.

[0078] In certain embodiments, activation of two adjacent chambers of the four independent inflatable chambers in the flexible linear actuator causes bending of the flexible linear actuator, wherein the bending angle of the flexible linear actuator varies depending on the applied air pressure in both independent inflatable chambers (e.g., FIG. 2E). For example, the flexible linear actuator may be bent at an angle of greater than or equal to 2 degrees, greater than or equal to 5 degrees, greater than or equal to 10 degrees, greater than or equal to 20 degrees, greater than or equal to 50 degrees, or greater than or equal to 75 degrees. The flexible linear actuator may be bent at an angle of less than or equal to 120 degrees, less than or equal to 110 degrees, less than or equal to 100 degrees, or less than or equal to 90 degrees. Combinations of the above- referenced ranges are also possible (e.g., greater than or equal to 2 degrees and less than or equal to 120 degrees, greater than or equal to 5 degrees and less than or equal to 110 degrees). Other ranges are also possible.

[0079] In some embodiments, a sleeve adjacent an expandable actuator is a Kirigami sleeve in a unidirectional triangle shape. Fabrication of the sleeve (e.g., the Kirigami sleeve) may involve laser cutting and engraving. The laser cutting may use a CO2 laser. The laser cutting and engraving may involve laser cutting lines and engraving lines.

[0080] Air pressure may be applied to expand the sleeve (e.g., the kirigami sleeve), such that the air pressure is large enough to expand the sleeve so as to anchor the system in a location internal to a subject, and / or the air pressure is not so large as to cause harm to the location internal to the subject. For example, in some embodiments, the air pressure applied to expand the sleeve may be greater than or equal to 10 kPa, greater than or equal to 20 kPa, greater than or equal to 25 kPa, greater than or equal to 30 kPa, or greater than or equal to 40 kPa. In some embodiments, the air pressure applied to expand the sleeve may be less than or equal to 100 kPa, less than or equal to 90 kPa, less than or equal to 80 kPa, less than or equal to 70 kPa, less than or equal to 60 kPa, or less than or equal to 50 kPa. Combinations of the abovereferenced ranges are also possible (e.g., greater than or equal to 10 kPa and less than or equal to 100 kPa, greater than or equal to 20 kPa and less than or equal to 90 kPa). Other ranges are also possible. In certain embodiments, the air pressure applied to expand the sleeve may be 25 kPa or 50 kPa. Applied air pressure to a sleeve (e.g., a Kirigami sleeve) may lead to a diameter increase by a suitable percentage large enough to anchor the system in a location internal to a subject, and not so large as to cause harm to the location internal to the subject. For example, in some embodiments, applying air pressure to a sleeve may lead to a diameter increase of greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, or greater than or equal to 25%. In some embodiments, applying air pressure to a sleeve may lead to a diameter increase of less than or equal to 50%, less than or equal to 45%, less than or equal to 40%, less than or equal to 35%, or less than or equal to 30%. Combinations of the above -referenced ranges are also possible (e.g., greater than or equal to 5% and less than or equal to 50%, greater than or equal to 10% and less than or equal to 45%). Other ranges are also possible.

[0081] Applied air pressure to a sleeve (e.g., a Kirigami sleeve) may lead to a popping angle relative to a tangent of the circular cross-section of the non-expanded sleeve large enough to anchor the system in a location internal to a subject, and not so large as to cause harm to the location internal to the subject. For example, in some embodiments, applying air pressure to a sleeve may lead to a popping angle of greater than or equal to 10 degrees, greater than or equal to 20 degrees, or greater than or equal to 30 degrees. In some embodiments, applying air pressure to a sleeve may lead to a popping angle of less than or equal to 60 degrees, less than or equal to 50 degrees, or less than or equal to 40 degrees. Combinations of the abovereferenced ranges are also possible (e.g., greater than or equal to 10 degrees and less than or equal to 60 degrees, greater than or equal to 20 degrees and less than or equal to 50 degrees). Other ranges are also possible.

[0082] In certain embodiments, the air pressure applied to the sleeve and the diameter increase of the sleeve achieves a clinically acceptable friction force in a pulling test. For example, in some embodiments, the diameter increase of the sleeve achieves a friction force in a pulling test of greater than or equal to 1.0 N, greater than or equal to 1.2 N, greater than or equal to 1.4 N, or greater than or equal to 1.5 N. In some embodiments, the diameter increase of the sleeve achieves a friction force in a pulling test of less than or equal to 2.0 N, less than or equal to 1.8 N, or less than or equal to 1.6 N. Combinations of the abovereferenced ranges are also possible (e.g., greater than or equal to 1.0 N and less than or equal to 2.0 N, greater than or equal to 1.2 N and less than or equal to 1.8 N). Other ranges are also possible. In certain embodiments, the diameter increase of the sleeve achieves a friction force in a pulling test of 1.5 N.

[0083] In certain embodiments, the diameter increase of the expandable actuator with the sleeve (e.g., Kirigami sleeve) required to achieve a clinically acceptable friction force is significantly less than the diameter increase of an expandable actuator without a sleeve required to achieve a clinically acceptable friction force.

[0084] In certain embodiments, the sleeve comprises or is made of silicone rubber.

[0085] In certain embodiments, the systems described herein may be used to anchor one or more systems to a surface of tissue e.g., in the GI tract. In some cases, the system may comprise an anchoring mechanism (e.g., a hook, a mucoadhesive). The anchoring mechanism may be located, e.g., on one or both ends of the system, e.g., on the first and / or the second expandable actuator. The anchoring mechanism may be located in a channel extending through an expandable actuator (e.g., in a channel extending through the flexible linear actuator, the first expandable actuator, and the second expandable actuator) and may be deployed, e.g., by action of a spring, at a location internal to a subject. This action of the spring may be by removal (e.g., dissolution) of a support material from the spring at a location internal to a subject.

[0086] In some embodiments, the system may be configured to anchor to a location internal to a subject (e.g., a tissue at a location internal to a subject). In some embodiments, the system may comprise one or more tissue interfacing components comprising one or more anchoring mechanisms (e.g., a hook, a mucoadhesive). Other embodiments are also possible comprising at least one anchoring mechanism associated with a system. In some embodiments, the anchoring mechanism comprises a hook (e.g., a hooked needle).

[0087] In some embodiments, the anchoring mechanism (and / or the system comprising the anchoring mechanism) is configured to be retained at a location internal to a subject. For example, in some embodiments, the anchoring mechanism engages with a surface (e.g., a surface of a tissue) at the location internal to the subject such that it is retained at that location.

[0088] Advantageously, the systems comprising one or more anchoring mechanisms described herein may be inserted into a surface of tissue at a location internal to a subject, and may maintain contact with the tissue under relatively high applied forces and / or relatively high change in orientation (e.g., by compressive forces exerted by the gastrointestinal tract and / or under high flow rates within the gastrointestinal tract). In some embodiments, the systems described herein do not substantially block orifices within the gastrointestinal tract (e.g., in the pylorus) e.g., restricting flow and enabling longer contact times. In certain embodiments, natural replenishment of the walls of the gastrointestinal tract may permit desirable detachment and / or expulsion of the systems described herein, without the need for surgical and / or endoscopic retrieval.

[0089] For example, in some embodiments, the anchoring mechanism may be inserted into a surface of a tissue at a location internal to a subject and maintains contact with the tissue (e.g., the system remains anchored) under a change of orientation of the system of greater than or equal to 1 degree, greater than or equal to 2 degrees, greater than or equal to 5 degrees, greater than or equal to 10 degrees, greater than or equal to 15 degrees, greater than or equal to 20 degrees, greater than or equal to 25 degrees, greater than or equal to 30 degrees, greater than or equal to 45 degrees, greater than or equal to 60 degrees, greater than or equal to 75 degrees, or greater than or equal to 85 degrees. In certain embodiments, the system may remain anchored under a change of orientation of the system of less than or equal to 90 degrees, less than or equal to 85 degrees, less than or equal to 75 degrees, less than or equal to 60 degrees, less than or equal to 45 degrees, less than or equal to 30 degrees, less than or equal to 25 degrees, less than or equal to 20 degrees, less than or equal to 15 degrees, less than or equal to 10 degrees, less than or equal to 5 degrees, or less than or equal to 2 degrees. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 1 degree and less than or equal to 90 degrees, greater than or equal to 1 degree and less than or equal to 45 degrees, greater than or equal to 2 degrees and less than or equal to 30 degrees). Other ranges are also possible.

[0090] In some embodiments, the system comprises two or more anchoring mechanisms. In certain embodiments, the force required to dislodge the anchoring mechanism (e.g., the normal retention force, the orthogonal retention force) may be increased by increasing the number of anchoring mechanisms associated with the system. Without wishing to be bound by theory, the spacing between anchoring mechanisms may be related to the retention force (e.g., the normal retention force, the orthogonal retention force) of the system. In some embodiments, the system may have an average spacing between anchoring mechanisms of greater than or equal to 0.1 mm, greater than or equal to 0.2 mm, greater than or equal to 0.3 mm, greater than or equal to 0.4 mm, greater than or equal to 0.5 mm, greater than or equal to 0.6 mm, greater than or equal to 0.7 mm, greater than or equal to 0.8 mm, greater than or equal to 0.9 mm, greater than or equal to 1 mm, greater than or equal to 1.2 mm, greater than or equal to 1.4 mm, greater than or equal to 1.5 mm, greater than or equal to 1.6 mm, greater than or equal to 1.8 mm, or greater than or equal to 2 mm. In certain embodiments, the system may have an average spacing between anchoring mechanisms of less than or equal to 2.5 mm, less than or equal to 2 mm, less than or equal to 1.8 mm, less than or equal to 1.6 mm, less than or equal to 1.4 mm, less than or equal to 1.2 mm, less than or equal to 1 mm, less than or equal to 0.9 mm, less than or equal to 0.8 mm, less than or equal to 0.7 mm, less than or equal to 0.6 mm, less than or equal to 0.5 mm, less than or equal to 0.4 mm, less than or equal to 0.3 mm, or less than or equal to 0.2 mm. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 0.1 mm and less than or equal to 2.5 mm, greater than or equal to 1 mm and less than or equal to 1.5 mm). Other ranges are also possible.

[0091] The anchoring mechanism may have any suitable dimension and / or shape. For example, in some embodiments, the largest dimension (e.g., the length) of the tissue interfacing component comprising the anchoring mechanism may be less than or equal to 1 cm, less than or equal to 0.8 cm, less than or equal to 0.6 cm, less than or equal to 0.5 cm, less than or equal to 0.4 cm, less than or equal to 0.3 cm, less than or equal to 0.25 cm, less than or equal to 0.23 cm, or less than or equal to 0.2 cm. In certain embodiments, the largest dimension (e.g., the length) of the tissue interfacing component comprising the anchoring mechanism may be greater than or equal to 0.15 cm, greater than or equal to 0.2 cm, greater than or equal to 0.23 cm, greater than or equal to 0.25 cm, greater than or equal to 0.3 cm, greater than or equal to 0.4 cm, greater than or equal to 0.5 cm, greater than or equal to 0.6 cm, or greater than or equal to 0.8 cm. Combinations of the above -referenced ranges are also possible (e.g., greater than or equal to 0.2 cm and less than or equal to 1 cm, greater than or equal to 0.15 cm and less than or equal to 1 cm). Other ranges are also possible.

[0092] In some embodiments, the anchoring mechanism has a particular anchor length. By way of example, for an anchoring mechanism comprising a hook, the anchor length corresponds to the largest cross-sectional dimension of a bent length of the hook (e.g., a diameter of the hook, not including any unbent portion). In certain embodiments, the anchor length is greater than or equal to 10 microns, greater than or equal to 20 microns, greater than or equal to 23 microns, greater than or equal to 25 microns, greater than or equal to 30 microns, greater than or equal to 34 microns, greater than or equal to 35 microns, greater than or equal to 40 microns, greater than or equal to 50 microns, greater than or equal to 60 microns, greater than or equal to 70 microns, greater than or equal to 80 microns, greater than or equal to 90 microns, greater than or equal to 100 microns, greater than or equal to 120 microns, greater than or equal to 140 microns, greater than or equal to 160 microns, greater than or equal to 180 microns, greater than or equal to 200 microns, or greater than or equal to 225 microns. In certain embodiments, the anchor length is less than or equal to 250 microns, less than or equal to 225 microns, less than or equal to 200 microns, less than or equal to 180 microns, less than or equal to 160 microns, less than or equal to 140 microns, less than or equal to 120 microns, less than or equal to 100 microns, less than or equal to 90 microns, less than or equal to 80 microns, less than or equal to 70 microns, less than or equal to 60 microns, less than or equal to 50 microns, less than or equal to 40 microns, less than or equal to 30 microns, or less than or equal to 20 microns. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 10 microns and less than or equal to 250 microns). Other ranges are also possible.

[0093] In some cases, the anchoring mechanism may be configured to have an optimal penetration depth (e.g., the depth at which the anchoring mechanism is disposed beneath the surface of a tissue located internal to a subject). In some embodiments, the anchoring mechanism has a penetration depth of greater than or equal to 0.5 mm, greater than or equal to 0.6 mm, greater than or equal to 0.7 mm, greater than or equal to 0.8 mm, greater than or equal to 0.9 mm, greater than or equal to 1 mm, greater than or equal to 1.2 mm, greater than or equal to 1.4 mm, greater than or equal to 1.5 mm, greater than or equal to 1.7 mm, greater than or equal to 1.9 mm, greater than or equal to 2 mm, greater than or equal to 2.2 mm, greater than or equal to 2.4 mm, greater than or equal to 2.5 mm, greater than or equal to 3 mm, greater than or equal to 3.5 mm, greater than or equal to 4 mm, greater than or equal to 4.5 mm, or greater than or equal to 5 mm. In certain embodiments, the anchoring mechanism has a penetration depth of less than or equal to 6 mm, less than or equal to 5 mm, less than or equal to 4.5 mm, less than or equal to 4 mm, less than or equal to 3.5 mm, less than or equal to 3 mm, less than or equal to 2.5 mm, less than or equal to 2.4 mm, less than or equal to 2.2 mm, less than or equal to 2 mm, less than or equal to 1.9 mm, less than or equal to 1.7 mm, less than or equal to 1.5 mm, less than or equal to 1.4 mm, less than or equal to 1.2 mm, less than or equal to 1 mm, less than or equal to 0.9 mm, less than or equal to 0.8 mm, less than or equal to 0.7 mm, or less than or equal to 0.6 mm. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 0.5 mm and less than or equal to 6 mm, greater than or equal to 0.9 mm and less than or equal to 2.5 mm). Other ranges are also possible. Without wishing to be bound by theory, the displacement of the tissue may be greater than or equal to the penetration depth of the anchoring mechanism. By way of example only, and in a particular set of embodiments, the anchoring mechanism may displace tissue up to 14 mm to achieve a penetration depth of e.g., up to 4 mm.

[0094] Advantageously, the systems comprising an anchoring mechanism described herein may be retained for a relatively long period of time under physiological conditions and fluid flows (e.g., exposed to a fluid flowing at approximately 0.1 m / s). For example, in some embodiments, the system comprising an anchoring mechanism is retained at a surface of tissue located internal to a subject for greater than or equal to 1 hour, greater than or equal to 2 hours, greater than or equal to 4 hours, greater than or equal to 8 hours, greater than or equal to 12 hours, greater than or equal to 24 hours, greater than or equal to 2 days, greater than or equal to 3 days, greater than or equal to 5 days, greater than or equal to 7 days, or greater than or equal to 10 days. In certain embodiments, the system is retained for less than or equal to 14 days, less than or equal to 10 days, less than or equal to 7 days, less than or equal to 5 days, less than or equal to 3 days, less than or equal to 2 days, less than or equal to 24 hours, less than or equal to 12 hours, less than or equal to 8 hours, less than or equal to 4 hours, or less than or equal to 2 hours. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 1 hour and less than or equal to 14 days). Other ranges are also possible. In some cases, the anchoring mechanism may be configured to be retained for relative very long periods of time under physiological conditions and fluid flows. For example, in certain embodiments, the anchoring mechanism may be retained at a surface of tissue location internal to a subject for greater than or equal to 1 month, greater than or equal to 2 months, greater than or equal to 3 months, greater than or equal to 6 months, or greater than or equal to 1 year. In some embodiments, the anchoring mechanism may be retained at a surface of tissue location internal to a subject for less than or equal to 2 years, less than or equal to 1 year, less than or equal to 6 months, less than or equal to 3 months, or less than or equal to 2 months. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 1 hour and less than or equal to 2 years, greater than or equal to 1 month and less than or equal to 2 years). Other ranges are also possible.

[0095] The anchoring mechanisms described herein may comprise any suitable material. In some embodiments, the anchoring mechanism material is relatively non-degradable. In certain embodiments, the anchoring mechanism may be configured to degrade within a certain period of time. In some embodiments, the anchoring mechanism is configured to degrade within one or more ranges of time described above in the context of being retained. For example, in some embodiments, the anchoring mechanism is configured to degrade (e.g., such that the system is no longer retained at the location internal to the subject) in greater than or equal to 1 hour, greater than or equal to 2 hours, greater than or equal to 4 hours, greater than or equal to 8 hours, greater than or equal to 12 hours, greater than or equal to 24 hours, greater than or equal to 2 days, greater than or equal to 3 days, greater than or equal to 5 days, greater than or equal to 7 days, or greater than or equal to 10 days. In certain embodiments, the anchoring mechanism is configured to degrade in less than or equal to 14 days, less than or equal to 10 days, less than or equal to 7 days, less than or equal to 5 days, less than or equal to 3 days, less than or equal to 2 days, less than or equal to 24 hours, less than or equal to 12 hours, less than or equal to 8 hours, less than or equal to 4 hours, or less than or equal to 2 hours. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 1 hour and less than or equal to 14 days). Other ranges are also possible. In some cases, the anchoring mechanism may be configured to degrade (e.g., such that the system is no longer retained at the location internal to the subject) in greater than or equal to 1 month, greater than or equal to 2 months, greater than or equal to 3 months, greater than or equal to 6 months, or greater than or equal to 1 year. In some embodiments, the anchoring mechanism may degrade in less than or equal to 2 years, less than or equal to 1 year, less than or equal to 6 months, less than or equal to 3 months, or less than or equal to 2 months. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 1 hour and less than or equal to 2 years, greater than or equal to 1 month and less than or equal to 2 years). Other ranges are also possible.

[0096] In some embodiments, the system is configured to facilitate locomotion at a location internal to a subject. In some embodiments, the system comprises a flexible linear actuator, a first expandable actuator and a second expandable actuator. For example, as shown illustratively in FIG. 29 A, system 100 comprises flexible linear actuator 110 having a first end and a second end. In some embodiments, first expandable actuator 120 is adjacent to (e.g., and operably linked to) the first end of flexible linear actuator 110. In some embodiments, second expandable actuator 130 is adjacent to (e.g., and operably linked to) the second end of flexible linear actuator 110.

[0097] As used herein, when a component is referred to as being “adjacent” another component, it can be directly adjacent to (e.g., in contact with) the component, or one or more intervening components also may be present. A component that is “directly adjacent” another component means that no intervening component(s) is present.

[0098] In some embodiments, the flexible linear actuator is configured to stretch (e.g., linearly) and / or bend. For example, in some embodiments, the flexible linear actuator is configured to bend as shown illustratively in FIG. 29B. The flexible linear actuator may undergo any suitable degree of bending (e.g., greater than or equal to 0 degrees, greater than or equal to 10 degrees, greater than or equal to 30 degrees, greater than or equal to 45 degrees, greater than or equal to 60 degrees, greater than or equal to 75 degrees, greater than or equal to 90 degrees, greater than or equal to 110 degrees, greater than or equal to 120 degrees, greater than or equal to 135 degrees, greater than or equal 170 degrees).

[0099] In some embodiments, as shown illustratively in FIG. 29C, system 100 comprises first sleeve 125 adjacent first expandable actuator 120 and second sleeve 135 adjacent second expandable actuator 130. In some embodiments, first sleeve 125 and / or second sleeve 135 comprise a texture and / or material that enhances friction with tissue at the location internal to the subject (e.g., upon inflation (or radial expansion / engagement) of expandable actuator 120 and / or expandable actuator 130). In some embodiments, first sleeve 125 and / or second sleeve 135 comprise a patterned surface. In some embodiments, the patterned surface comprises a plurality of protrusions 145 (e.g., a Kirigami-type surface). In some embodiments, the plurality of protrusions are selected from the group consisting of particles, posts, nanoneedles, microneedles, nanograss, micrograss, pores, cavities, wells, interconnected pores, interconnected cavities, grooves, ridges, and cutouts. The plurality of protrusions may have any suitable cross-sectional shape including circular, oval, triangular, irregular, trapezoidal, square or rectangular, or the like. Each protrusion may be continuous (with respect to the surface material) with a neighboring protrusion or may be discrete. In an exemplary set of embodiments, the patterned surface comprises a Kirigami-type surface.

[0100] In some embodiments, the plurality of protrusions protrude (e.g., protrude further) upon expansion (e.g., inflation) of an expandable actuator. In some embodiments, in a nonexpanded configuration of an expandable actuator, the plurality of protrusions do not substantially protrude from the surface. Advantageously, upon expansion of the expandable actuator, the plurality of protrusions of the surface (e.g., a Kirigami-type surface) may increase the friction with a contacting surface (e.g., a surface of a location internal to a subject such as a wall of the small intestine) e.g., thereby reducing and / or eliminating slippage of the system during, prior to, and / or after locomotion of the system. In some embodiments, the sleeve further comprises a plurality of raster lines.

[0101] In some embodiments, the flexible linear actuator comprises a spring. In some embodiments, as shown illustratively in FIG. 29D, flexible linear actuator 110 comprises channel 150. In some embodiments, the spring may be disposed within channel 150. In some embodiments, the spring comprises a superelastic material (e.g., nitinol). In certain embodiments, the spring comprises a material selected from the group consisting of nitinol, metals, polymers, and combinations thereof. In certain embodiments, the spring may have a suitable spring constant.

[0102] In some embodiments, channel 150 extends through at least a portion of the first expandable actuator and / or the second expandable actuator.

[0103] In some embodiments, the flexible linear actuator further comprises a plurality of fibers disposed on a surface of the flexible linear actuator. In an exemplary set of embodiments, the fibers comprise Kevlar. The fibers may have any suitable characteristic fiber angles and / or thickness.

[0104] In some embodiments, the system comprises two or more pneumatic chambers associated with the flexible linear actuator, the first expandable actuator, and / or the second expandable actuator. For example, at least a portion of the flexible linear actuator may comprise a pneumatic chamber (e.g., as shown in the photo in FIG. 2B). The pneumatic chambers may be used, in some embodiments, to generate locomotion of the system. For example, at least one of the two or more pneumatic chambers may be activated such that the flexible linear actuator bends (e.g., as shown illustratively in FIG. 29B). In some embodiments, at least one of the two or more pneumatic chambers may be activated such that the flexible linear actuator extends (e.g., linearly). In some embodiments, the two or more pneumatic chambers may be used to bend and extend the flexible linear actuator. In some embodiments, each pneumatic chamber is individual addressable (e.g., and is in fluidic communication with a pump).

[0105] In some embodiments, the first expandable actuator and / or the second expandable actuator comprises an expandable balloon such as a donut-shaped balloon. Other shapes and configurations are possible. In some embodiments, upon expansion of one or more of the expandable actuators, the system locomotes along the location internal to the subject. In some embodiments, each expandable actuator is in fluidic communication with a pump (e.g., configured to inflate / deflate the expandable actuator). While balloon-type expandable actuators are generally described, other expandable actuators are also possible.

[0106] In some embodiments, the system further comprises one or more caps associated with one or more of the expandable actuators.

[0107] In some embodiments, a controller is associated with the system (e.g., in electronic, pneumatic, fluidic, and / or chemical communication with the system). Advantageously, the controller may be designed to be generally adaptable to any robotic system with similar structure of actuators or fewer. In some embodiments, the controller provides precise pneumatic control, such as a bi-directional closed-loop pressure control.

[0108] In some embodiments, the system described herein comprises a (micro)controller and / or (micro)processor. In some embodiments, the controller is configured (e.g., programmed) to receive and transmit data commands to / from one or more components of the system and / or a joystick (or other control device such as a smartphone or other consumer electronic device). In some embodiments, the data includes one or more signals from one or more sensors. In some embodiments, the controller may be configured to adjust various parameters based on external metrics e.g., in response to a signal from a sensor in electrical communication with the controller, in response to a signal from a user. The embodiments described herein can be implemented in any of numerous ways. For example, the embodiments may be implemented by any suitable type of analog and / or digital circuitry. In some embodiments, the embodiments may be implemented using hardware or a combination of hardware and software. When implemented using software, suitable software code can be executed on processing circuitry including any suitable processor (e.g., a microprocessor) or collection of processors, whether provided in a single computer or distributed among multiple computers (or other consumer electronic devices). It should be appreciated that any component or collection of components that perform the functions described above can be generically considered as one or more controllers that control the above-discussed functions. The one or more controllers can be implemented in numerous ways, such as with dedicated hardware or with one or more processors programmed using microcode or software to perform the functions recited above. The one or more embodiments can be implemented in numerous ways, such as with dedicated hardware, or with general purpose hardware (e.g., one or more processors) that is programmed using microcode or software to perform the functions recited above.

[0109] In some embodiments, the systems described herein comprise wireless capabilities for enabling suitable communication with other devices / systems (e.g., for controlling aspects of the controller, controlling locomotion of the system, controlling a source of electromagnetic radiation, controlling a sensor or other component). Wireless devices are generally known in the art and may include, in some cases, LTE, WiFi and / or Bluetooth systems. In some embodiments, the systems and / or devices described herein comprise such a wireless device (e.g., a short-range wireless component).

[0110] In some embodiments, the embodiments described herein may be configured to adjust various parameters in response to an input from a user and / or a signal from a sensor and / or an externally located consumer electronic device.

[0111] In some embodiments, the system is associated with and / or comprises a power source. The power source may include any appropriate material(s), such as one or more batteries, photovoltaic cells, etc. Non-limiting examples of suitable batteries include Li-polymer (e.g., with between 100 and 1000 mAh of battery life), Li-ion, nickel cadmium, nickel metal hydride, silver oxide, or the like. In some cases, the battery may apply a voltage (e.g., to a degradable material as described herein) in response to a physiological and / or external metric and / or signal (e.g., by a user). For example, the voltage may be used to trigger the exit of the resident structure by e.g., applying a voltage to thermally sensitive degradable component as described herein. For example, the average magnitude of the voltage applied to the degradable component(s) may be between 0.001 to 0.01 V, between 0.01 to 0.1 V, between 0.1 V and 10.0 V, between 1.0 V and 8.0 V, between 2.0 V and 5.0 V, between 0.1 V and 5.0 V, between 0.1 V and 1.5 V, between 0.1 V and 1.0 V, between 1.0 V and 3.0 V, between 3.0 V and 8.0 V, or any other appropriate range.

[0112] Any electronic component circuitry may be implemented by any suitable type of analog and / or digital circuitry. For example, the electronic component circuitry may be implemented using hardware or a combination of hardware and software. When implemented using software, suitable software code can be executed on any suitable processor (e.g., a microprocessor) or collection of processors. The one or more electronic components can be implemented in numerous ways, such as with dedicated hardware, or with general purpose hardware (e.g., one or more processors) that is programmed using microcode or software to perform the functions recited above.

[0113] In this respect, it should be appreciated that one implementation of the embodiments described herein comprises at least one computer-readable storage medium (e.g., RAM, ROM, EEPROM, flash memory or other memory technology, or other tangible, non-transitory computer-readable storage medium) encoded with a computer program (i.e., a plurality of executable instructions) that, when executed on one or more processors, performs the above-discussed functions of one or more embodiments. In addition, it should be appreciated that the reference to a computer program which, when executed, performs any of the above-discussed functions, is not limited to an application program running on a host computer. Rather, the terms computer program and software are used herein in a generic sense to reference any type of computer code (e.g., application software, firmware, microcode, or any other form of computer instruction) that can be employed to program one or more processors to implement aspects of the techniques discussed herein.

[0114] Some embodiments relate to methods for locomoting an enteroscopic robot (e.g., such as the systems comprising a flexible linear actuator, a first expandable actuator and a second expandable actuator, described herein). In some embodiments, the enteroscopic robot may be controlled by performing one or more of the following steps: expanding the first expandable actuator, extending the flexible linear actuator, expanding the second expandable actuator, deflating the first expandable actuator, shrinking the flexible linear actuator, and deflating the second expandable actuator.

[0115] As used herein, the term “active pharmaceutical ingredient” (also referred to as a “drug” or “therapeutic agent”) refers to an agent that is administered to a subject to treat a disease, disorder, or other clinically recognized condition, or for prophylactic purposes, and has a clinically significant effect on the body of the subject to treat and / or prevent the disease, disorder, or condition.

[0116] According to some embodiments, the composition and methods described herein are compatible with one or more therapeutic, diagnostic, and / or enhancement agents, such as drugs, nutrients, microorganisms, in vivo sensors, and tracers. In some embodiments, the active substance, is a therapeutic, nutraceutical, prophylactic or diagnostic agent. While much of the specification describes the use of therapeutic agents, other agents listed herein are also possible.

[0117] Agents can include, but are not limited to, any synthetic or naturally-occurring biologically active compound or composition of matter which, when administered to a subject (e.g., a human or nonhuman animal), induces a desired pharmacologic, immunogenic, and / or physiologic effect by local and / or systemic action. For example, useful or potentially useful within the context of certain embodiments are compounds or chemicals traditionally regarded as drugs, vaccines, and biopharmaceuticals, Certain such agents may include molecules such as proteins, peptides, hormones, nucleic acids, gene constructs, etc., for use in therapeutic, diagnostic, and / or enhancement areas, including, but not limited to medical or veterinary treatment, prevention, diagnosis, and / or mitigation of disease or illness e.g., HMG co-A reductase inhibitors (statins) like rosuvastatin, nonsteroidal anti-inflammatory drugs like meloxicam, selective serotonin reuptake inhibitors like escitalopram, blood thinning agents like clopidogrel, steroids like prednisone, antipsychotics like aripiprazole and risperidone, analgesics like buprenorphine, antagonists like naloxone, montelukast, and memantine, cardiac glycosides like digoxin, alpha blockers like tamsulosin, cholesterol absorption inhibitors like ezetimibe, metabolites like colchicine, antihistamines like loratadine and cetirizine, opioids like loperamide, proton-pump inhibitors like omeprazole, anti(retro)viral agents like entecavir, dolutegravir, rilpivirine, and cabotegravir, antibiotics like doxycycline, ciprofloxacin, and azithromycin, anti-malarial agents, and synthroid / levothyroxine); substance abuse treatment (e.g., methadone and varenicline); family planning (e.g., hormonal contraception); performance enhancement (e.g., stimulants like caffeine); and nutrition and supplements (e.g., protein, folic acid, calcium, iodine, iron, zinc, thiamine, niacin, vitamin C, vitamin D, and other vitamin or mineral supplements).

[0118] In certain embodiments, the active substance is one or more specific therapeutic agents. As used herein, the term “therapeutic agent” or also referred to as a “drug” refers to an agent that is administered to a subject to treat a disease, disorder, or other clinically recognized condition, or for prophylactic purposes, and has a clinically significant effect on the body of the subject to treat and / or prevent the disease, disorder, or condition. Listings of examples of known therapeutic agents can be found, for example, in the United States Pharmacopeia (USP), Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th Ed., McGraw Hill, 2001; Katzung, B. (ed.) Basic and Clinical Pharmacology, McGraw-Hill / Appleton & Lange; 8th edition (September 21, 2000); Physician’s Desk Reference (Thomson Publishing), and / or The Merck Manual of Diagnosis and Therapy, 17th

[0119] ed. (1999), or the 18th ed (2006) following its publication, Mark H. Beers and Robert Berkow (eds.), Merck Publishing Group, or, in the case of animals, The Merck Veterinary Manual, 9th ed., Kahn, C.A. (ed.), Merck Publishing Group, 2005; and “Approved Drug Products with Therapeutic Equivalence and Evaluations," published by the United States Food and Drug Administration (F.D.A.) (the “Orange Book"). Examples of drugs approved for human use are listed by the FDA under 21 C.F.R. §§ 330.5, 331 through 361, and 440 through 460, incorporated herein by reference; drugs for veterinary use are listed by the FDA under 21 C.F.R. §§ 500 through 589, incorporated herein by reference. In certain embodiments, the therapeutic agent is a small molecule. Exemplary classes of therapeutic agents include, but are not limited to, analgesics, anti-analgesics, anti-inflammatory drugs, antipyretics, antidepressants, antiepileptics, antipsychotic agents, neuroprotective agents, anti-proliferatives, such as anti-cancer agents, antihistamines, antimigraine drugs, hormones, prostaglandins, antimicrobials (including antibiotics, antifungals, antivirals, antiparasitics), antimuscarinics, anxioltyics, bacteriostatics, immunosuppressant agents, sedatives, hypnotics, antipsychotics, bronchodilators, anti-asthma drugs, cardiovascular drugs, anesthetics, anticoagulants, inhibitors of an enzyme, steroidal agents, steroidal or non-steroidal anti- inflammatory agents, corticosteroids, dopaminergics, electrolytes, gastro-intestinal drugs, muscle relaxants, nutritional agents, vitamins, parasympathomimetics, stimulants, anorectics and anti-narcoleptics. Nutraceuticals can also be incorporated into the drug delivery device. These may be vitamins, supplements such as calcium or biotin, or natural ingredients such as plant extracts or phytohormones.

[0120] In some embodiments, the therapeutic agent is one or more antimalarial

[0121] drugs. Exemplary antimalarial drugs include quinine, lumefantrine, chloroquine, amodiaquine, pyrimethamine, proguanil, chlorproguanil-dapsone, sulfonamides such as sulfadoxine and sulfamethoxypyridazine, mefloquine, atovaquone, primaquine, halofantrine, doxycycline, clindamycin, artemisinin and artemisinin derivatives. In some embodiments, the antimalarial drug is artemisinin or a derivative thereof. Exemplary artemisinin derivatives include artemether, dihydroartemisinin, arteether and artesunate. In certain embodiments, the artemisinin derivative is artesunate.

[0122] In another embodiment, the therapeutic agent is an immunosuppressive

[0123] agent. Exemplary immunosuppressive agents include glucocorticoids, cytostatics (such as alkylating agents, antimetabolites, and cytotoxic antibodies), antibodies (such as those directed against T-cell recepotors or 11-2 receptors), drugs acting on immunophilins (such as cyclosporine, tacrolimus, and sirolimus) and other drugs (such as interferons, opioids, TNF binding proteins, mycophenolate, and other small molecules such as fingolimod).

[0124] In certain embodiments, the therapeutic agent is a hormone or derivative thereof. Non-limiting examples of hormones include insulin, growth hormone (e.g., human growth hormone), vasopressin, melatonin, thyroxine, thyrotropin-releasing hormone, glycoprotein hormones (e.g., luteinzing hormone, follicle-stimulating hormone, thyroid-stimulating hormone), eicosanoids, estrogen, progestin, testosterone, estradiol, cortisol, adrenaline, and other steroids.

[0125] In some embodiments, the therapeutic agent is a small molecule drug having molecular weight less than about 2500 Daltons, less than about 2000 Daltons, less than about 1500 Daltons, less than about 1000 Daltons, less than about 750 Daltons, less than about 500 Daltons, less or than about 400 Daltons. In some cases, the therapeutic agent is a small molecule drug having molecular weight between 200 Daltons and 400 Daltons, between 400 Daltons and 1000 Daltons, or between 500 Daltons and 2500 Daltons. In some embodiments, the therapeutic agent is selected from the group consisting of active pharmaceutical agents such as insulin, nucleic acids, peptides, bacteriophage, DNA, mRNA, human growth hormone, monoclonal antibodies, adalimumab, epinephrine, GLP-1 Receptor agoinists, semaglutide, liraglutide, dulaglitide, exenatide, factor VIII, small molecule drugs, progrstin, vaccines, subunit vaccines, recombinant vaccines, polysaccharide vaccines, and conjugate vaccines, toxoid vaccines, influenza vaccine, shingles vaccine, prevnar pneumonia vaccine, mmr vaccine, tetanus vaccine, hepatitis vaccine, HIV vaccine Ad4-env Clade C, HIV vaccine Ad4-mGag, dna vaccines, rna vaccines, etanercept, infliximab, filgastrim, glatiramer acetate, rituximab, bevacizumab, any molecule encapsulated in a nanoparticle, epinephrine, lysozyme, glucose-6-phosphate dehydrogenase, other enzymes, certolizumab pegol, ustekinumab, ixekizumab, golimumab, brodalumab, gusellu,ab, secikinumab, omalizumab, tnf-alpha inhibitors, interleukin inhibitors, vedolizumab, octreotide, teriperatide, crispr cas9, insulin glargine, insulin detemir, insulin lispro, insulin aspart, human insulin, antisense oligonucleotides, and ondansetron.

[0126] In an exemplary embodiment, the therapeutic agent is insulin.

[0127] As used herein, a “fluid” is given its ordinary meaning, i.e., a liquid or a gas. A fluid cannot maintain a defined shape and will flow during an observable time frame to fill the container in which it is put. Thus, the fluid may have any suitable viscosity that permits flow. If two or more fluids are present, each fluid may be independently selected among essentially any fluids (liquids, gases, and the like) by those of ordinary skill in the art.

[0128] EXAMPLES

[0129] The following examples are intended to illustrate certain embodiments described herein, including certain aspects of the present invention, but do not exemplify the full scope of the invention.

[0130] Diagnosing and treating small intestinal disorders such as bleeding, inflammatory bowel disease, and tumors presents significant challenges due to the difficulty of accessing this anatomical compartment. To address these challenges, BIOSENTER, a bioinspired soft enteroscopic robot, is provided to facilitate deep small intestine procedures, overcoming the limitations in locomotion, steering, and intervention faced by existing soft robotic systems. BIOSENTER features a hollow-cylinder design that includes a linearly deformable soft pneumatic actuator as the robotic body, two radially expandable soft pneumatic actuators wrapped with Kirigami sleeves as the robotic head and tail, a central hollow channel for housing accessory endoscopic tools, and a control box for navigation. Inspired by the snake's adaptive locomotion in dynamic environments, the robotic body incorporates a fiber-reinforced actuator with four embedded inflatable chambers. This multi-component design allows for versatile movements, including steering and axial expansion. The dynamic Kirigami sleeves achieve clinically acceptable friction force of -1.5N on intestinal mucosa with radial expansion while minimizing tissue distention. A reinforced central channel supports the passage of tools, facilitating diagnostic and therapeutic (i.e., theranostic) interventions. The control box supports efficient locomotion and steering, achieving autonomous speeds of -100 mm / min in vitro, -43 mm / min in tissue-covered tubing. The BIOSENTER robot successfully navigated the collapsed, tortuous small intestine over a distance of 2 meters within 11 minutes, with gentle forward pushing forces ranging from 2.2 to 6.4 N in pig studies. In vivo pig studies demonstrated BIOSENTER's potential for tissue biopsies, localized drug delivery, and real-time visualization in the deep intestinal region, without causing tissue overdistention and damage.

[0131] Introduction

[0132] The small intestine (SI) is a tube-like organ approximately 6 meters long, which folds many times to fit inside the abdomen Diagnosing and treating small intestinal disorders such as bleeding, polyps, inflammatory bowel disease (IBD), and tumors (Figure 1A) poses significant challenges due to the limitations in accessing and navigating this anatomical compartment using traditional endoscopy. Although capsule endoscopy can visualize the entire SI, it is limited in performing real-time biopsy sampling and treatment.

[0133] Flexible enteroscopy systems, such as push, double-balloon, single-balloon, and spiral enteroscopes, have been developed for diagnostics and therapeutics (i.e., theranostics) in the SI. Among these, the double-balloon enteroscope (DBE) is the only non-surgical tool reported for examining the entire SI either down the esophagus or up through the anus, using sequences of balloon inflation and deflation along with push-and-pull maneuvers (Figure 8). Despite eliminating the need for abdominal surgery, the DBE procedure may cause complications including tissue overdistention, intestinal bleeding, and bowel perforation, mainly due to the device's rigidity and limited maneuverability. Additionally, DBE procedures often result in incompleteness due to slippage, a consequence of pressure-limited latex expansion balloons designed with smooth surface finish. The need for extensive training also hinders the practicality of DBE for routine use, as the operational complexity prolongs the procedure times to over 90 minutes.

[0134] Soft robots, designed with mechanical moduli similar to that of biological tissues, have emerged in various biomedical applications, including wearable robots for rehabilitation, robotic sleeves for cardiac assist, robotic catheters for cardiac interventions and robotic endoscopes for sigmoidoscopy. An ideal soft robotic system for effective enteroscopic procedures should autonomously navigate the long, coiled intestine with gentle pushing during forward locomotion, minimize slippage on mucus-covered lumens during pulling, and perform visualization, biopsy, and localized intervention treatments. However, designing a system that achieves both agile locomotion and steering, as well as effective theranostics in the SI, remains challenging.

[0135] One significant challenge faced by most soft robots is incomplete procedures similar to those in DBE due to the slippage of elastomeric materials on the mucus-covered mucosal tissue. Although patterned features on the balloon can enhance the friction force during push-and-pull maneuvers, this design still involves significant tissue distention during the procedure. Similarly, strategies for enlarging tissue contact can enhance locomotion but still present the risk of tissue overdistention. The recently reported use of Kirigami structures incorporated into soft actuators may enhance friction force without causing tissue overdistention during locomotion, but may also introduce additional risks, such as tissue disruption, that need to be mitigated.

[0136] Another challenge is that most soft robotic designs, if applied as enteroscopes, present operational complexity. For example, while current soft robotic colonoscopy presents steering capability, it lacks autonomous locomotive ability, which may minimize the effectiveness of interventional procedures if adapted for applications in the SI. Bioinspired endoscopic robotic designs show promise for full automation, but these prototypes may have limited locomotive ability in the long, coiled, and collapsed intestinal environment. For example, earthworm-inspired soft robots, which have been recently reported to enhance friction force by integrating a Kirigami or bristle structure, have been developed for environmental applications 22, 23). Although promising for autonomous locomotion during enteroscopic applications in the SI, their single-chamber robotic body design exhibits limited manipulation freedom due to the lack of steering capability.

[0137] The third challenge facing soft robots is that most designs rarely accommodate endoscopic accessories while enabling locomotion. Endoscopic accessories, such as forceps, alligators, and cameras, are usually rigid and not stretchable, which hinders robotic locomotion if not integrated properly. Recently reported soft robotic bronchoscopes demonstrated the integration of endoscopic tools such as cameras, lights, and alligators; however, these integrations lack the freedom to guide along the channel, particularly during pneumatic actuation, which can cause the lumen to collapse. Although the multistage endoscopic robot, designed for peristaltic crawling to inspect the small intestine, enables the integration of endoscopic tools with guiding flexibility, its rigid body would induce tissue overdistention if applied in vivo. Collectively, no soft robotic system has been developed to realize non-invasive diagnostic and localized treatment procedures in the SI with in vivo validation (Table 1).

[0138] Nature is a rich source of inspiration for overcoming design limitations involving locomotion, steering, and friction-enhancement designs. For example, snakes can efficiently adapt their locomotion modes in dynamic environments. Figure lB_i shows a gait sequence of snakes using their ventral muscles, specifically the costocutaneous muscles, which connect the ribs to the skin and scales, to propel themselves forward in rectilinear locomotion. Figure lB_ii depicts a snake utilizing its lateral muscles, such as the oblique muscles, to steer. These muscles contract on one side of the body while relaxing on the opposite side, allowing the snake to bend and change direction. Figure IB _iii illustrates how snakes orient their scales to increase friction anisotropy, enabling them to propel themselves forward. Inspired by these natural mechanisms, these examples report the development of BIOSENTER, a bioinspired soft enteroscopic robot to facilitate locomotion, steering, and interventions in the deep SI (Figures 1C and ID). BIOSENTER features a hollow-cylinder design with the following components: a linearly deformable soft pneumatic actuator as the robotic body for axial expansion and steering (Figure IE), two radially expandable soft pneumatic actuators wrapped with Kirigami sleeves as the robotic head and tail for anchoring (Figure IF), a central hollow channel for housing accessory endoscopic tools (Figure 1G), and a control box with wireless joystick controller for navigation (Figure lD_i and ii). The robot can achieve autonomous speeds of -100 mm / min in vitro (Figure 1H), -43 mm / min in tissue-coved tubing. The robot successfully navigated the collapsed, tortuous small intestine over a distance of 2 meters within 11 minutes, with gentle forward pushing forces ranging from 2.2 to 6.4 N in pig studies. Through in vivo pig studies, these examples demonstrated BIOSENTER's potential for tissue biopsies, localized drug delivery, and realtime visualization in the deep intestinal compartment, without causing tissue overdistention or damage.

[0139] Results

[0140] BIOSENTER design: The BIOSENTER system comprises a soft robot, and a control box with a wireless joystick controller.

[0141] Design, fabrication, and assembly of the soft robot: Double-balloon enteroscopes are medical devices developed for interventional procedures within the deep small intestine, requiring precise navigation through complex digestive luminal passages. To meet the desired features of enteroscopes and the anatomical characteristics of the human body, the soft robot was designed as a hollow cylindrical structure with an initial length (Lo) of 95 mm and an outer diameter (Do) of 14 mm (Figure 1C). This design ensures safe navigation through narrow luminal passages, such as the esophagus which generally has an inner diameter greater than 20 mm.

[0142] To facilitate locomotion in the intestinal lumen, the robot consists of three pneumatically driven segments: one Kevlar-fiber reinforced soft actuator with four embedded independently inflatable chambers as the robotic body for elongation and steering (Figure IE), and two radially expandable soft actuators wrapped with Kirigami sleeves as the robotic head and tail for tissue anchoring (Figure IF). The dynamic Kirigami sleeves achieve clinically acceptable friction force of -1.5 N (discussed in Design and performance test of the anchoring unit) on intestinal mucosa with radial expansion while minimizing tissue distention. The robot’s locomotion is facilitated through the active inflation and deflation of six pneumatic chambers using eight embedded airway channels in the tail unit (Figure 1C).

[0143] Specifically, two channels power the tail anchoring unit (Figure 9_iii), while four channels pass through the tail unit (Figures 9_ii and 9_iv) to power the four chambers of the body actuator. The last two channels run through the entire body (Figure 9_i) to power the head anchoring unit. Figure 1H presents the sequence of forward robotic locomotion in an intestinal phantom: (i) robot entering the SI, (ii) tail unit inflation for anchoring, (iii) body unit inflation for elongation, (iv) head unit inflation for anchoring, (v) deflation of both tail unit and body unit for forward crawling, and (vi) tail unit inflation for anchoring again and head unit deflation.

[0144] The hollow channel at the center of the robot is designed with a diameter of 6 mm for housing accessory endoscopic tools such as cameras, biopsy alligators, lights, drug spray ports, and air channels (Figure 1C and G). To prevent the hollow channel from collapsing during actuators pressurization and to create a stretchable barrier between the robot and the accessories, it was reinforced with an embedded homemade superelastic nitinol spring (tsPring= 0.4 mm, DSpring= 6.2 mm) (Figure 1C). This reinforced channel supports the passage of tools to facilitate theranostic interventions in the SI (Figure 1G).

[0145] The robot can be fabricated as a single-part device (the white one denoted in Figure 10) using 3D- printing (TruSil Shore 20A; Spectroplast, Switzerland). Each component (i.e., robotic head, body, tail, and End-Cap) can be fabricated out of a silicone-based rubber (Double Elite 22; Zhermack SpA, Italy) via injection molding (Figure 11) as a more accessible alternative and then assembled using silicone glue (the pink one denoted in Figure 10, with the assembly process shown in Figure 12A). To facilitate the seamless alignment of pneumatic channels, each end of the injection-molded components that need to be connected to the subsequent part is designed with a 2 mm mating region for precise overlap (Figure 12A_i-iii). In both 3D- printing and injection molding processes, eight silicone pipes (0 = 1 mm, Uxcell) along with a 3D-printed flexible Seal-Cap, were glued to the tail end of the device (Figure 1 l_iv) and connected to the control box's pumps and valves via Luer locks for pneumatic actuation. Kevlar fiber was then used to reinforce the body actuator, while a superelastic nitinol spring and an accessory cap (Figure 12B) are inserted into the robot’s hollow channel of the robot. Kirigami sleeves were then attached to the head and tail, completing the assembly process for deployment. Additional Details provides detailed information on injection molding and device assembly.

[0146] Design and characterization of the body unit: Rectilinear locomotion in snakes relies on the contraction and relaxation of ventral muscles along their segmented bodies, generating waves of movement that propel them forward. Additionally, snakes can steer by selectively contracting lateral muscles on one side of their body while relaxing the muscles on the opposite side to turn (Figure lB_ii). Inspired by this locomotion mechanism, the body unit was designed as a linear actuator with four pneumatic chambers (Figures 2A and 2B), enabling versatile robotic maneuverability in the long and coiled intestine, including axial expansion and steering.

[0147] We have previously introduced a fiber-reinforced linear soft actuator to facilitate the deposition of drug depots in the tubular mucosa of the GI tract. Utilizing the fiber-reinforced technique, the cylindrical elastomeric body was fabricated with guiding rails for Kevlar fiber reinforcement arranged in a double-helical pattern at a characteristic angle of P = 14° (Figure 2A). This pattern is repeated four times at equiangular intervals (i.e., 90°) around the cylinder to facilitate extension actuation along the length of the component.

[0148] In contrast to existing fiber-reinforced actuators that consist of one or two pneumatic chambers, the four-chamber design functions as a snake’s lateral muscles, achieving 360° continuous planar access with non-isobaric chamber activation as demonstrated in the Design and performance characterization of the control box section. This design also enables a precise 45° discrete resolution under isobaric chamber activation (Figure 2C), further facilitating precise steering and manipulation in the complex environment of the small intestine. These chambers, with a 1.5 mm wall thickness, are designed as curved trapezoidal prisms symmetrically positioned around the spring-reinforced hollow structure.

[0149] Additional Details and Figure 11C provide details on the fabrication of the body unit using injection molding. Four soft embedded channels (0 = 1mm) are incorporated through the tail actuator, each connecting separately to one of the chambers (Figure 9-ii and iv) for transferring pneumatic pressure for inflation and deflation.

[0150] We characterized the body unit’s performance under different actuation modes using the 3D-printed version. This design allows the four pneumatic chambers to be activated independently. For example, when fully activated under 180 kPa, the body unit can axially elongate to -1.35 times its original length (Figure 2D), enabling forward crawling. This elongation is greater than that achieved in the diagonally two-chamber activated mode (Figure 13). To enable a bending motion, one, two, or three pneumatic chambers can be activated (Figure 2E, Figures 14, and 15). Notably, the half-activated mode can achieve a bending angle of 112° under 180 kPa (Figure 2E). During actuation, the chambers’ cross-sectional area remains constant. This multimodal actuation approach allows for higher manipulation precision in the long and coiled small intestine, potentially ensuring comprehensive and accurate diagnostics and treatment.

[0151] Design and performance test of the anchoring unit: The balloon materials and smooth surface design of both DBE and soft robots exhibit a low friction coefficient with the mucus-covered intestinal mucosa. This leads to incomplete procedures due to pressurelimited balloon slippage during push-and-pull maneuvers (Panel 8 in Figure 8). To achieve clinically acceptable friction force of greater than 1.2 N on intestinal mucosa with radial expansion while minimizing tissue distention, it was designed with both head and tail anchoring units with radially expandable balloon actuators encased in buckling-induced Kirigami sleeves (Figures IF and 3A). The balloon actuators, featuring a 1.5 mm wall thickness, were designed as a hollow-cylinder structure. Additional Details and Figures 11B and 11D describe the details of the balloon actuator fabrication using injection molding. Kirigami, a Japanese art form similar to origami but involving cutting as well as folding, has been applied in this design to harness local elastic instabilities for versatile shape transformation from flat to 3D architectures. Buckling-induced Kirigami metasurfaces have been engineered to generate high friction forces, making them suitable for biomedical and robotic applications. In this study, a snake skin-inspired Kirigami structure was developed that wraps around the tail and the head actuators to minimize the balloon’s radial expansion while providing sufficient friction force against the SI mucosa (Figures 3C and 3H).

[0152] Additional Details and Figure 16 provide detailed information on the Kirigami design.

[0153] We explored various patterns and cutting directions for needles with similar heights (h) to optimize the performance of Kirigami sleeves in terms of radial expansion and popping angle, with the goal of enhancing the friction force on the mucosa. These factors are critical for ensuring that the device remains securely anchored during locomotion sequences without causing excessive tissue damage. The friction force was evaluated through a pulling test on ex vivo small intestinal tissues (Figure 17A). Patterns were prioritized to harness the elastic instabilities of buckling-induced Kirigami, with the unidirectional triangle pattern demonstrating the optimal popping angle and friction force (Figure 17B_i). Modifications in needle cut directions and row arrangements (i.e., multidirectionality) significantly altered the popping behavior and adversely affected the friction force on the tissue compared to the unidirectional pattern (Figure 17C). For subsequent tests, the unidirectional triangle- shaped Kirigami pattern was selected (i.e., Pattern i in Figure 17) with a unit cell parameter of y = 30°, h ~1.6 mm, and <5 / 1 = 0.16 based on its performance in ex vivo tissue tests. However, other patterns are also possible. In this context, y is the needle cut angle, h is the needle height, I is the triangular unit needle side length, and <5 is the hinge width between adjacent cuts (Figure 3B).

[0154] We also investigated the impact of Kirigami sheet thickness on radial expansion, popping angle, and friction force. At the same pressure level (e.g., 50 kPa), balloon actuators encased in thinner Kirigami sheets exhibited greater radial expansion and popping angle due to their lower mechanical modulus (Figure 18). However, under identical radial expansion conditions, thinner sheets demonstrated limited anchoring capability, while thicker sheets (>0.005”) generally used higher pneumatic pressures to achieve similar radial expansion (Figure 19), pushing the limits of the pneumatic system. Consequently, a Kirigami sheet thickness of 0.003” (i.e., the green sheet) was selected for subsequent tests.

[0155] We examined the radial expansion and popping angle of the unidirectional triangleshaped Kirigami sleeve at various pressure levels: P = 0, 25, and 50 kPa (Figure 3C). Here, P = 0 kPa represents the undeformed state, while P = 50 kPa corresponds to the fully deployed configuration. This example compared experimental images of the Kirigami sleeves with numerical snapshots from non-linear finite element (FE) simulations, which revealed that the Kirigami sleeve starts as a flat structure and transforms into 3D configurations with buckled-out needles upon pressurization of the actuator (Figure 3D). The evolution of radial expansion (er=D / Do) and the popping angle (0) as functions of actuator pressure (P) is detailed in Figure 3E. Both experimental and simulation results show a gradual nonlinear increase in both erand 0 due to the out-of-plane buckling of the needles, followed by a plateau at higher pressures (>40 kPa), reaching maximum values of sr_max=1.3 and ^max = 43°. These findings demonstrate a qualitative agreement between FE simulations and experimental results (Figure 3C-E), suggesting that this approach has the potential to expedite the iteration of Kirigami-balloon designs for various biomedical applications.

[0156] We then characterized the friction force of the unidirectional triangle-shaped Kirigami sleeve at various pressure levels. At an actuation pressure of 50 kPa, the pop-up needles generated a friction force of 1.25 N against the slippery mucosal wall (Figures 3F and 3G), which is slightly higher than the clinically acceptable value, and resulted in a diameter increase of about 30% (Figure 3E and 3H_ii). Further pressure increases beyond 40-50 kPa did not further enhance the friction force (Figure 3H) due to the absence of additional radial expansion or significant increases in the popping angle (Figure 3E). Instead, higher inflation pressure (e.g., >90 kPa) increases the risk of Kirigami hinge fracture due to concentrated stress (Figure 20A). Laser engraving the external surface of Kirigami needles with raster lines (0.25 mm spacing) further enhanced the friction force to ~1.5 N (Figure 3B and 3F_ii. Additionally, enlarging the size of the Kirigami pattern increased the friction force (Figure 20B), further ensuring reduced risk of balloon slippage and procedural completeness with minimal tissue stretching. Upon pressure release, the buckled-out needles returned to their original undeformed shape.

[0157] To realize a fully autonomous BIOSENTER system, the device-tissue engagement may be further improved beyond the current -1.5 N anchoring force, despite its in vitro and ex vivo performance. This improvement could be achieved by optimizing the Kirigami design using Artificial Intelligence (Al)-assisted multidirectional Kirigami design for enhanced surface friction. While the multidirectional Kirigami patterns explored for this study did not achieve enhanced needle activation and friction force, as shown in Figure 16B and Eq. 1-4 in Additional Details, it is believed the optimal designs may use, for example, a multidirectional pattern with unequal activation strain.

[0158] In contrast, anchoring units without Kirigami sleeves under the same level of radial expansion provided a friction force of approximately 0.6 N (referenced as 'w / o Kirigami' in Figures 3F), a value that increases the risk of an incomplete procedure. To achieve a comparable anchoring force of -1.5 N (indicated by the gray line in Figure 21A), the untreated anchoring actuator generally used a radial expansion with a diameter increase of 150% at 50 kPa (Figure 31, Figures 21B and 21C), leading to significant tissue distention (Figure 3I_ii). A larger deviation in diameter change was observed at high-pressure levels (e.g., ~50 kPa, Figure 21B), due to the highly nonlinear response exhibited of the 3D-printed pneumatic actuator.

[0159] Design and performance test of the spring: To support the translation of the BIOSENTER robot for SI theranostics, this example incorporated a spring-reinforced hollow channel (d = 6 mm) in the robot’s center to accommodate various applicationspecific accessories (Figure 1G). This spring was designed to withstand large deformations while maintaining the structural integrity of the hollow channel (Figure 4A-C). This structure also creates a stretchable separation layer between the robot body and the non-stretchable accessories, allowing for unimpeded deformations. This example used superelastic nitinol wires with a diameter of 0.381 mm (0.015 in) to fabricate the reinforcement spring (Dspring=6.2 mm), which was inserted into the hollow channel to secure itself onto its inner wall (Figure 22). When the actuators were pressurized, the inner hollow chambers collapsed without the spring (Figures 4B_i and 4C_i). However, with the spring, their structural integrity was maintained, preventing the inner channel from collapsing (Figures 4B_ii and 4C_ii). In the case of both elongation and bending, accessories without the spring structure became stuck in the channels upon pressurization, while the spring structure ensured that they could move freely to facilitate enteroscopic procedures.

[0160] We further assessed the extension and bending capabilities of the Kevlar-reinforced extension body with enteroscopic tools (e.g., camera cable or forceps) inserted into the hollow channel. As shown in Figure 4D, the body unit equipped with the superelastic spring structure demonstrated a maximum elongation of 30.7%, compared to 18.8% for the unit without the spring, while carrying a non- stretchable camera cable.

[0161] Moreover, these evaluations revealed that the spring structure minimally impacted the bending performance (Figure 4E). These results ensure that the spring design has minimal effect on the robot’s locomotion and steering.

[0162] Design and performance characterization of the control box: Operating a DBE typically requires two trained specialists: an endoscopist for push-and-pull maneuvers and an assistant to control balloon inflation and deflation. This process demands extensive training to achieve precise steering and procedural accuracy. To reduce operational complexity for endoscopists and to enable the system’s potential for full autonomy, a control box was developed for the robotic procedure in the GI tract (Figure 5A). This control box, equipped with a wireless joystick controller, offers streamlined and precise control of the robot's locomotion modes, steering direction, and anchoring units’ expansion levels. With the integration of an image processing unit, this system can achieve fully autonomous operation.

[0163] The control box contains a custom 2-layer printed circuit board (PCB), 10 three-way valves, 4 pumps, and plumbing components (see Additional Details). The PCB includes a power management unit connected to the power supply, a microcontroller unit (MCU, Teensy 4.0) that sends commands to the valves and pumps, and motor drivers (Digikey DRV8231ADDAR) that measure and control the real-time current drawn by the pumps (Figures 5A_iii). Figure 23 provides a circuit schematic with details of the components used in the PCB.

[0164] The three-way valves are connected to the PCB’s output ports via transistor arrays to implement different actuation sequences (Figure 5A_iii and Figure 23). The silicone air tubes are connected to pumps through a combination of three-way valves to enable active inflation and deflation of all the chambers (Figure 5A_i and 5A_ii). Their actuation speed and pressure can be adjusted by changing the pumps’ drive voltage and limit current (Figure 24) through the PCB, respectively. Additional Details below and Figure 25 detail the plumbing architecture, active inflation and deflation sequences.

[0165] To ensure compatibility with various soft robotic prototypes, this example implemented a plug-and-play interface on the control box utilizing Luer Locks (Figure 5A_i). Each chamber of the soft robot, equipped with male Luer Locks through silicone pipes, seamlessly connected to the corresponding female Luer Locks on the control box, allowing for the rapid swapping of different robot prototypes (Figure 5A_i).

[0166] The battery-powered joystick controller includes a PCB with an MCU, Bluetooth module, knobs, and buttons (Figure 5A_iv) that were programmed (code uploaded on Github) to deliver wireless commands to the control box for various locomotion modes, providing a user-friendly interface for enteroscopic procedures. This enables actions such as real-time steering (Figure 5B) and switching of the crawling direction through the controller. Figure 26 provides a circuit schematic of the component details used for the joystick. To achieve closed-loop feedback and circumvent parasitic air leakage in the pneumatic system, three pressure sensors embedded in the PCB were connected to each actuator (Figure 5A_ii and 5A_iii). This allowed for precise control of each chamber’s pressure and robust robotic locomotion.

[0167] In a clinical setting, endoscopists operate the DBE for interventional procedures with visual feedback from endoscopic cameras. To align with the surgical workflow, this example implemented an open-loop controller for the soft robot to assess steering precision and dexterity and validate locomotion and steering performance using the control box. Specifically, the robot was deployed in a section of 20-mm tubing with its tail unit fully actuated to grip the tubing wall. User input from the joystick controller directly modulated the actuator chambers’ volumes to control the steering direction. A 1-mm forceps was guided through the hollow channel to target several 1-cm holes cut at 45-degree intervals around a circle on a piece of acrylic board, 3 cm away from the base of the soft robot (Figure 5C). Results showed that a single user could maneuver the forceps through 5 holes in 33 seconds (Figure 5C). This maneuverability can benefit various endoscopic interventions, such as polyp removal, demonstrated in vitro by steering the forceps to grab an object randomly placed in front of the robot within 12 seconds (Figure 5D). This capability is enhanced by the robot’s non-isobaric activation of two adjacent chambers, which allow for 360° continuous planar access.

[0168] We also evaluated the robot’s locomotion through in vitro, ex vivo, and in vivo experiments utilizing the control box. A preprogrammed command (Figure 6A) was wirelessly delivered from the joystick controller to the control box to manage the robot’s locomotion. To demonstrate its autonomous navigation potential, we first conducted locomotion tests in clear plastic tubing (d=20 mm) that was straight on a level plane, inclined about 30°, and curved with a 15 cm radius of curvature, and Si-covered plastic tubing without tissue collapse (Figure 6B-D). For the ex vivo testing, the inside of the plastic tubing was covered with SI tissue to ensure no tissue collapse. The control box supported efficient locomotion, achieving autonomous speeds of -100 mm / min in vitro (Figure 6B-D), -43 mm / min in tissue-coved tubing (Figure 6E), and an assisted (with a gentle push similar to the DBE procedure) speed of -200 mm / min in pig studies (Figure 7A-C). To further validate the locomotion performance of the BIOSENTER robot in tortuous environments, we conducted DBE-like procedures on porcine intestinal models in vivo. Air tubes connected to the robot were enclosed in flexible PVC hose tubing (8 mm ID x 10 mm OD), enabling gentle push-pull manipulation through an additional balloon device attached to the end of the hose. The robot was inserted approximately one meter downstream from the start of the small intestine following laparotomy, where locomotion could be visualized. BIOSENTER robot successfully navigated the collapsed, tortuous small intestine over a distance of 2 meters within 11 minutes with gentle forward pushing of 2.2-6.4 N (Figure 31). The robot achieved locomotion at a minimum radius of curvature smaller than the average anatomical curvature of the small intestine (-1.25 cm) (Figure 30). This demonstrated its ability to traverse conditions representative of realistic intestinal anatomy. The speed difference between the in vitro and ex vivo studies is mainly due to the longitudinal stretchability of the soft tissue structure, which reduces the effective traversed distance per locomotion sequence. A tissue-pulling maneuver was performed to retrieve traversed SI after forward locomotion of 30 cm on the euthanasia pig (Figure 6F_i-vi). As shown in Figure 6F_vii, soft robots equipped with Kirigami sleeves (w Kirigami, 45-50 kPa) retrieved about 98% of the traversed tissue, significantly outperforming those without Kirigami sleeves at the same balloon expansion (w / o Kirigami, 15-20 kPa). To achieve a comparable retrieval performance, robots without Kirigami sleeves required full expansion (about four times, w / o Kirigami, 45-50 kPa) (Figures 6F_vii).

[0169] However, this resulted in plastic deformation of the intestinal tissue and an increase in the intestinal diameter (Figures 6F_viii). Additionally, while larger lumen diameters resulted in reduced friction for both kirigami and non-kirigami balloons at full expansion (Figure 32), the diameter had minimal impact on push-and-pull-based locomotion as long as the intestinal tissue remained in a collapsed state rather than inflated. The friction force remained sufficiently high to enable successful tissue retrieval, and thus did not hinder locomotion performance under the tested anatomical conditions. These results demonstrated the efficacy of the control box and bioinspired robotic design in enhancing BIOSENTER’ s tissue retrieval efficiency during enteroscopic intervention.

[0170] Safety: To assess the safety of Kirigami sleeves on the tissue mucosa during in vivo procedures (Figure 7A), tissue sections were harvested, processed, and stained with hematoxylin and eosin. A pathologist (blinded to the status of the samples) conducted a histological assessment and found no differences between the control and treated tissues in terms of inflammation and mucosal integrity (Figure 7B). Additionally, with the assistance of the control box, no overdistention was observed during the procedure.

[0171] In vivo demonstrations

[0172] BIOSENTER’ s design holds potential for a range of applications, including tissue biopsies, localized drug delivery, and real-time lumen visualization in the deep intestinal compartment. Studies for demonstrating these applications were performed on sedated pigs or post-euthanasia, with the robot inserted through a 0.5-cm incision in the stomach wall to access the SI via a ventral midline laparotomy. Pig models were chosen for the in vivo studies because of their GI tract's anatomical similarity to that of humans.

[0173] As previously discussed, diagnostics and in situ disease treatment in the SI can be challenging due to limitations in accessing this anatomical compartment. The BIOSENTER system offers the potential for lumen visualization and in- situ treatment of intestinal conditions. By integrating lighting and camera systems into its hollow structure, BIOSENTER effectively visualizes the target intestinal compartment and assists with localized procedures (Figure 7E). When combined with a drug delivery tube, the BIOSENTER robot can spray a mock drug (green or blue food dye) onto targeted mucosal regions. Figure 7F presents the localized drug spray on the SI mucosa. This performance suggests that BIOSENTER can facilitate the treatments of localized injured mucosa, such as intestinal bleeding and perforations, which are life-threatening conditions requiring timely monitoring and clinical treatment. Additionally, when equipped with forceps, BIOSENTER can perform tissue biopsies from local intestinal mucosa tissue (Figure 7G_i) or polyps induced by sutures (Figure 7G_ii) in the deep intestinal region e.g., without the need for open chest surgery. Based on its high accuracy and effectiveness in performing these clinically-relevant tasks, the BIOSENTER system has the potential to represent a new paradigm for deep intestinal procedures.

[0174] Summary

[0175] This study reports the development of BIOSENTER, a bioinspired soft enteroscopic robot, designed to enhance locomotion, steering, and intervention in the deep small intestine of a porcine model. Potential applications include tissue biopsies, localized drug delivery, and real-time visualization in the deep intestinal compartment. This system could facilitate the clinical management of various health conditions, such as intestinal bleeding, localized treatment of IBD, and monitoring of inflammation in the deep intestine.

[0176] Based on results, it is anticipated that the BIOSENTER could be integrated with

[0177]

[0178] to conduct interventional

[0179]

[0180] in the deep intestinal segments with safety, user-friendliness, and a

[0181]

[0182] .. Overall, this device will offer both diagnostic and

[0183]

[0184] for small intestinal conditions in a non- surgical manner.

[0185] MATERIALS AND METHODS

[0186] Soft robot fabrication, and control box design and fabrication can be found in the Additional Details.

[0187] Kirigami fabrication: Utilizing Matlab and Autodesk Fusion 360, all Kirigami sleeves were designed with script-calculated parameters and fabricated them from thin polyester plastic sheets (McMaster-Carr, 9513K115) via laser cutting. As shown in Figure 16A, the sheets are cut (power = 12%, speed = 100%, PPI = 250) and raster engraved (power = 5%, speed = 100%, PPI = 250) with a laser cutter (Universal laser cutter). The cut sheets were then wrapped around the anchoring unit balloons.

[0188] Numerical Finite Element Analysis. All the simulations were carried out using the commercial FE package Autodesk Fusion 360 Simulation Extension. Constructed FE models of the elastomer actuator and the Kirigami plastic shell to investigate the deformation response of the anchoring unit.

[0189] • Material Models:

[0190] o Polyester Plastic: Linear elastic material model with a density of 1.13x 103kg / m3, Young’s modulus of 3655 MPa, and Poisson’s ratio of 0.4. The shell section had a thickness of 0.127 mm.

[0191] o Elastomer: Incompressible two-parameter Mooney-Rivlin hyperelastic material with a Poisson’s ratio of v0=0.499 and a density of 1000 kg / m3. The constitutive behavior was captured using directly imported uniaxial test data.

[0192] • Mesh setup:

[0193] o Mesh elements with an absolute size of 1 mm were selected with curved elements enabled. A maximum turn angle of 60° was used on curved surfaces. Adjacent mesh size ratio and aspect ratio were set to a maximum of 3 and 20, respectively.

[0194] • Simulation Setup:

[0195] o Solver: quasi- static event simulation model.

[0196] o Constraints: the surfaces on both ends of the balloon actuator and the base face of the Kirigami sheet were fixed.

[0197] o Contact Interactions: a separation contact type was used between the actuator and the Kirigami sheet with a friction coefficient of 0.2.

[0198] o Load Application: pressure load was applied to the inner surface of the balloon actuator using a linear ramp divided into 15 substeps. The deformation of the balloon and the Kirigami sheet was captured as a function of the applied pressure.

[0199] This setup enabled the accurate simulation of the deformation response of the anchoring unit under various pressure loads, providing valuable insights into the mechanical behavior of the system.

[0200] Customized setups for ex- vivo characterization of anchoring units. A manual mechanical testing stage (Mark- 10, Model E26) coupled with a force gauge (Mark- 10, Model M4-05) applied a precisely controlled pulling force (100 mm / min) to the anchoring units, which were inflated and inserted into a 20 cm segment of SI ex vivo tissue (see Figure 17A for the schematic of the testing setup). The force-time curve acquired during the test was analyzed by averaging the plateau regions to determine the average anchoring force.

[0201] In vivo terminal experiments. All terminal animal experiments were conducted following the approval of the experimental protocols by the Committee on Animal Care at the Massachusetts Institute of Technology. Swine models were chosen because of their anatomical similarity to humans in GLrelated studies. Randomization of the animals was not performed. Female Yorkshire swine (Cummings Veterinary School at Tufts University in Grafton, MA) weighing 43-90 kg and aged 3-6 months were used. The swine were placed on a liquid diet 24 h before the study and fasted on the day of the procedure. On the morning of the procedure, the swine were sedated using intramuscular injection of either 5 mg kg1telazol (tiletamine / zolazepam), 2 mg kg1xylazine and 0.04 mg kg1atropine, or 0.25 mg kg1midazolam and 0.03 mg kg1dexmedetomidine. After intubation, anesthesia was maintained with isoflurane (2-3% oxygen). Under anesthesia, vital signs were monitored and recorded every 15 min throughout the study. During the experiments, a ventral midline laparotomy was performed to access the small intestine (SI). A 0.5-cm incision was made in the stomach wall to insert the device into the SI. The device was retrieved by gently pulling it out of the SI after the study. Finally, the swine were euthanized.

[0202] Histology. Histological analysis was performed on intestinal tissue biopsies to assess the safety. Biopsies were taken from the mucosa treated with Kirigami sleeve from the small intestine within 10 minutes following euthanasia in a terminal experiment conducted in the lab's animal facility. The biopsies were fixed in formalin fixative (Sigma Aldrich) for 72 hours before transfer to 70% ethanol. Tissue samples were then embedded in paraffin, cut into 5-pm-thick tissue sections, stained with hematoxylin and eosin, and imaged using an Aperio AT2 Slide Scanner (Leica Biosystems). These samples were analyzed by a board-certified pathologist.

[0203] X-rav imaging

[0204] Images were acquired with x-ray tube settings of 55 kVp, 200 mA, and an exposure time of 200 ms with a 0.25-mm aluminum beam filter. Detector binning (4 by 4) was used for an isotropic resolution of 40.16 pm. Image reconstruction was performed using the Bruker NRecon software.

[0205] Statistical analysis

[0206] Statistical analyses were performed using GraphPad Prism software (GraphPad Software, Inc.). Results are depicted as mean ± standard deviation (SD). A two-sided student’s t-test was used to assess statistical differences, with p values < 0.05 considered statistically significant.

[0207] Code Availability

[0208] Code that supports the findings of this study is available at

[0209] https: / / github.com / jebran 10 / BIOSENTER.

[0210] ADDITIONAL DETAILS

[0211] Fabrication of the body unit, anchoring unit, and End- Cap using injection molding Body unit: This example employed injection molding as an accessible fabrication method. As shown in Figure 11C, this example designed a four-part mold where two complementary inserts are sandwiched between two mold halves, creating a cylindrical part with four chambers and a central hollow channel. The inserts have alignment features to ensure precise and consistent fabrication. Additionally, both inserts are designed with two through-holes for 1 mm steel rod sub-inserts to create the embedded air channels, allowing airflow through the separation walls to power the head anchor unit. Symmetrically positioned runners, sprues, and gates are strategically located at the parting line to simplify part removal and mold cleanup. The gate is placed on the outer walls of the mating region to prevent any defects in the actuator following the gate cut- off. This placement ensures that the silicone is injected from the tail end of the actuator's outer wall, flowing through the head end and filling up to the tail end of the inner walls (Figure 1 lC_iii).

[0212] Anchoring unit: As shown in Figures 11B and 11D, this example designed four-part molds for each of the head and tail anchor units. For these anchor units, two complimentary inserts are sandwiched between two mold halves, creating a three- walled cylindrical part. The runners, sprues, and gates are symmetrically placed at the parting line to facilitate easy removal and mold cleanup. The gates are strategically placed on the outer walls of the mating regions to avoid defects in the actuators after the gate cut-off. This placement ensures that the silicone is injected from the tail end of the actuator's outer wall, flowing through the head end and filling up to the tail end of the inner walls (Figures 1 lB_iii and HDJii).

[0213] End-Cap: The injection molded version of the robot included a fourth component, the End-Cap, to complete the robotic body and close the tail anchoring unit. As shown in Figure HE, this example designed a two- part mold for End-Cap units. Designed with a 2 mm complementary mating region featuring a distinct pattern, the End-Cap seamlessly integrates with the back end of the tail anchoring unit, ensuring precise alignment of the pneumatic pathways. The End-Cap has eight air inlets, each pair symmetrically placed around the central hollow structure.

[0214] All mold parts were designed with Autodesk Fusion 360 and 3D printed (Object 30 Pro, Stratasys) with VeroClear rigid plastic resin and a glossy finish to ensure a high-quality surface finish for the actuator injection molded parts. Before molding, each mold component was generously sprayed with a releasing agent (Universal Mold Release, Smooth-On) to facilitate effortless removal of the injection-molded part. The four-part mold was then assembled and clamped to ensure sufficient clamping force for the injection molding process.

[0215] We applied the necessary injection pressure to mold each unit with Elite Double 22 using a syringe. Following the injection process, the filled mold remained clamped for 30 minutes, surpassing the 20-minute setting time of Elite Double 22, ensuring the actuator was cured. These units were then demolded, and the gates were cut off.

[0216] Fabrication of the body unit, anchoring unit, and Seal-Cap using 3D printing.

[0217] Body unit: Alternatively, the body extension actuator can be 3D-printed as a hollow cylinder with four chambers capped with 2 mm end walls (TruSil Shore 20A; Spectroplast, Switzerland). To closely resemble the body actuator, each unit is printed with six input airway ports, each with a 1 mm diameter. Four of these air channels power the actuator chambers, while the remaining two traverse the chamber separation walls of the body unit.

[0218] Anchor units: Similarly, the anchoring units can be 3D-printed as hollow-cylinder objects (TruSil Shore 20A; Spectroplast, Switzerland). To ensure these units closely resemble the actuators of the BIOSENTER robot, each unit is printed with two input airway ports, each with a diameter of 1 mm.

[0219] Seal-Cap: Whether 3D-printed or injection molded, eight silicone tubes, each with a 1 mm outer diameter, are attached to the back end of soft robots for pneumatic control of all the chambers. To mitigate the risk of air leakage, a small flexible sealing unit, the Seal-Cap, is designed and 3D-printed (Elastic 50A Resin; Formlabs, USA) with eight matching air inlet holes akin to those on the End-Cap (Figure 28). In addition, the Seal-Cap is designed with a 0.5 mm deep cavity that is filled with silicone adhesive to eliminate air leakage at the edge of the silicone pipes and the robot.

[0220] Accessories Cap: To ensure precise placement of endoscopic accessories, a holder unit called Accessories Cap (Acc-Cap) is designed and 3D printed (Flexible 80A resin;

[0221] Formlabs, USA) (Figure 12BB). The front face of the Acc-Cap is designed with a conical shape to ease the robotic locomotion and traversal through the GI tract. The back end of the Acc-Cap is designed to fit tightly in the hollow channel of robots. A cross-sectional view shows that the air and fluid channels are strategically positioned to feed into the camera channel, facilitating the cleaning of the camera view and lens during enteroscopic procedures (Figure 12B-C).

[0222] Robot Assembly

[0223] After injection molding, each component is assembled to construct the complete robot. To enable seamless integration, all mating surfaces are designed with a 200 pm clearance between subsequent parts. As shown in Figure 12A, the positive mating region of the body unit is first treated with silicone adhesive (Sil-Poxy, Smooth-On) and inserted into the negative mating region of the head anchoring unit. To ensure precise alignment during assembly, a smooth 6 mm steel rod is inserted inside the hollow channel of all the individual parts, facilitating the assembling process. Then, the positive mating region of the tail anchoring unit is treated with Sil-Poxy and fitted into the back end of the body unit.

[0224] Following that, the End-Cap’s mating region is coated with Sil-Poxy and inserted at the back end of the tail actuator. Once assembled, the robot is left resting on the steel rod overnight (>12 hrs) to cure thoroughly, ensuring robust bonding and structural integrity.

[0225] Silicone Tubing Attachment: To enable pneumatic control of each actuator and chamber, eight silicone tubes, each with a 1 mm diameter, are attached to the rear end of the robot. First, about 1 cm of the outer surface of the silicone tubing is coated with Sil-Poxy and inserted into the back end of the robot. The tubing is inserted through the Seal-Cap, End-Cap, and about halfway into the tail actuator. Subsequently, the Seal- Cap cavity is filled with Sil-Poxy and securely attached to the robot. The robot is left undisturbed overnight (> 12 hrs) to create a robust silicone seal barrier between the tubing and the robot body, ensuring optimal pneumatic functionality and minimizing the risk of air leaks.

[0226] At the opposite end, the silicone tubing is connected to Luer Locks using a short intermediate silicone pipe as an adaptor, featuring an inner diameter of 1 mm and an outer diameter of 3 mm (Uxcell). These Luer Locks serve as an interface for a modular plug-and-play mechanism with the control box, facilitating a reusable and versatile robotic control system.

[0227] Superelastic Reinforcement Spring Placement: Once the robot is assembled and connected to silicone tubing, the superelastic nitinol structure, still attached to its fabrication jig, is carefully inserted into the hollow channel of the robot. Upon insertion, the fixed ends of the spring are cut, releasing the spring. The released spring expands and firmly contacts the walls of the hollow channel, securing itself in place. Subsequently, the aluminum jig is removed, completing the installation process.

[0228] Keylar Fiber Reinforcement: To ensure uniform extension along the length of the device and prevent radial deformation, the body actuator is reinforced with Kevlar fiber (diameter = 0.1778 mm; Kevlar Sewing Thread, SGT Knots supply Co, NC). Both the 3D-printed and injection molded versions of the body actuator feature double-helical guiding rails for precise attachment of the Kevlar fiber (Figure 2A). Following these guide rails, Kevlar fiber is coated with the Sil-Poxy and attached to the body actuator. To ensure a robust attachment, the fiber is wound a few extra turns on each end of the body actuator after each helical threading. The part is then left undisturbed overnight (> 12 hrs) to cure.

[0229] Kirigami Sleeve Design: The head and the tail anchoring units of the assembled robot are covered with Kirigami sleeves, designed to overlap and snugly wrap around the actuator. A MATLAB script was developed to derive a needle height value constrained by the actuator length and circumference to generate whole numbers of Kirigami needle rows and columns, ensuring an end-to-end symmetric actuator sleeve. Considering an average SI wall thickness of 1.5 ± 0.5 mm, this example confined the needle height within the range of 1.5 mm < h < 2 mm. Utilizing Autodesk Fusion 360, all Kirigami sleeves were designed with script- calculated parameters and fabricated them from thin polyester plastic sheets (McMaster-Carr, 9513K115) via laser cutting. The sheets are cut (power = 12%, speed = 100%, PPI = 250) and raster engraved (power= 5%, speed = 100%, PPI = 250) with a laser cutter (Universal laser cutter). Then, the cut sheets are wrapped around the anchoring unit balloons.

[0230] To ensure proper adhesion and placement of the sleeve on the actuator, the Kirigami sleeve design sketches are parameterized to include multiple extra needle rows that perfectly overlap with themselves when wrapped around the balloon. In addition, the edges along the length of the sleeve sheet have an uncut margin of 2.5 mm on each side, extending 20 mm beyond the Kirigami cut region (Figure 16A). These extended margins are wrapped around the sheet and glued (Super glue, Loctite) to the first layer, ensuring that the Kirigami sleeves are closed and secured. The sleeves are further reinforced by the adhesion of the overlapping needle rows, perfectly matching the first layer. The overlapped region and the attachment bands are glued, creating a cylindrical shell around the actuators with a robust weld line. To prevent dislodgement during locomotion, one end of each anchoring unit’s Kirigami sleeve, closer to the body actuator, is glued to the Kevlar fiber bands. This attachment ensures the sleeves remain firmly in place throughout the robot’ s locomotion. The overlapped region ensures that the Kirigami sheet does not fail at the weld area of the sleeve, while still allowing the Kirigami feature to pop up during actuation.

[0231] The actuator balloons experience maximum deformation at the center of the thinwalled cylinder, symmetrically extending the circumference of the cylinder around the centerline. This deformation, when projected on an unwrapped 2D sheet, appears as a two-dimensional pattern. As shown in Figure 16B, the Kirigami sheet experiences maximum deformation along the centerline of its length, with almost no deformation along the borders. Approximating the curvature of the pressurized balloon with a triangle, an approximate strain for each direction can be calculated.

[0232] x: 41 = A d)) — = nd (1) = d / D® (2) _ I ~ y: Jw = 2j(d / 2)z+ = Jd2A (3)

[0233] + 1 - 1 (4)

[0234]

[0235] wtere DQ = diameter (5) d = change in diameter due to actuation (6) HQ = initial sleeve height (7) = change in t / ie sleeve width due to artaotimi (8) = strain in the defined x direction. (Figure 84) (9)

[0236]

[0237] = strain in the defined y direction (Figure 84) (10) Given the values of Ho and Do, it was observed that ey « exfor small values of changes in diameter d (Eq. 1-4). Since the projected sheet experiences strain predominantly along its length, it was ensured that the center of the Kirigami sheet is script-designed and cut end-to-end. The wrap-around margins are positioned at the borders to ensure that the sleeve remains on the actuator when inflated.

[0238] Accessories attachment: Finally, the desired accessory tool and the camera are carefully inserted into the hollow channel of the robot. Notably, all the accessories are fixed solely to the Acc-Cap, allowing the robot to navigate unhindered, particularly during the extension and bending phase.

[0239] Plumbing, Pipes, and Pumps

[0240] Eight silicone air tubes are connected to three mini pumps through a combination of 3-way valves in a closed-loop configuration, allowing for active inflation and deflation of all the chambers (Figure 25A). This configuration enables precise control of robotic locomotion speed, extension stride length, bending angle, and the expansion and engagement levels of the anchoring units and their Kirigami sleeves. An additional pump is used for enteroscopic inflation purposes. All the valves and pumps are powered and controlled by the main control board.

[0241] Pneumatic Logic: Each 3-way valve has a main port (M) that is connected to the second port (0) when the valve is off and to the third port (1) when the valve is on (Figure 25). Each actuator is controlled with a separate pump, inflation valve (lx), and deflation valve (Dx). For instance, the head anchoring unit is controlled with pump A, valve IA, and valve DA. The M-ports of the inflation and deflation valves are connected to the pumps, while the O-ports are left unconnected to serve as exhausts and fluid inlets, respectively. For the head and the tail anchoring units, the 1 -ports of the valves are connected to individual four-way junctions. These junctions in turn connect to the two pneumatic control pipes per actuator along with their respective pressure sensors. As for the body unit, the 1 -ports of the inflation and deflation valves are connected to a 4- way junction and a pressure sensor. The remaining two ports of the 4- way junction are then connected to 3-way junctions, each further connected to four 3-way valves (VBx) at their respective 1 -ports. Each body chamber is connected to the M-port of its corresponding VB, with the O-port left unconnected to atmospheric pressure. This intricate configuration allows for the independent connection of each actuator and chamber to the pressurized line, facilitating precise control over their operation. Active Inflation and Deflation: Each robot chamber is connected to both 3-way inflation and 3-way deflection valves. To pressurize any chamber, the inflation valve is activated while the deflation valve remains off (Figure 25D-E_left). Conversely, to actively deflate any chamber, the deflation valve is activated while the inflation valve is left off (Figure 25D-E_right). This setup establishes a direct connection between the pump and the actuator chamber, enabling rapid air expulsion compared to passive pressure-differential deflation. Consequently, this setup allows significantly quicker locomotion sequences.

[0242] Additionally, this architecture provides the capability to actively monitor and modify the activation level of each actuator and chamber, creating a robust and responsive closed-loop system.

[0243] Control box

[0244] PCB design: The PCB is designed to provide the user with a seamless interface to manipulate and operate the robot. It includes a power management unit (Figure 5A-iii and Figure 23A) that connects to a power supply. Two off-the-shelf buck converters generate two distinct power rails: one for the pumps (5- 9V) and one for the 6V components.

[0245] Additionally, the board incorporates two voltage regulators to provide stable 5V and 3.3V rails for the sensitive signal components. On the output side, JST jumpers facilitate connections to the pumps and 3-way valves. LED lights are added next to each jumper for color-coded indication of their active states.

[0246] The board is controlled with a Teensy 4.0 microcontroller that interfaces with buffered input and output signals. The Teensy issues command signals to the valves and pumps, transmitted via transistor arrays and motor controllers. Equipped with internal load- side current sensing, the motor controller chips allow real- time measurement of the current drawn by the pumps (VPROP-x signals). Given that the pumps can draw a maximum of ~1A, the current sense external resistors are selected to ensure the VPROP-x signals fall within the 0-3V range, compatible with the Teensy 4.0 input pins (max 3.3V). Additionally, the Teensy can set the current limit for the motor drivers, enabling precise pressure control for each actuator through the VREF-x signals. To eliminate the need for a digital-to-analog converter (DAC), a low-pass filter converts each VREF-x signal to an analog VREF for the chip. The PCB also accommodates three pressure sensors, each connected to one of the actuator lines. The pressure signals are converted from the 0-5V sensor range to a 0-3.3V range and buffered for Teensy inputs.

[0247] Lastly, the board integrates an off-the-shelf Bluetooth 5.0 module for wireless communication. Paired with a wireless joystick, the control box enables users to transmit locomotion commands wirelessly, effectively controlling the robot.

[0248] Housing: The control board, pumps, valves, and plumbing components are enclosed in an acrylic box. Designed with Autodesk Fusion 360, the Box features convenient finger joint interfaces, facilitating swift assembly and disassembly (Figure 5A, and Figure 27). The box has two levels: one for the PCB and one for the plumbing components.

[0249] Additionally, a small, dedicated compartment at the top of the box securely accommodates the robot. All the box parts and walls are laser cut out of an acrylic sheet with a 6 mm thickness. Screw-nut joints reinforce the structural integrity of the box. This design ensures a robust, easy- to-assemble housing for the robot's control and pneumatic systems, providing a reliable and user-friendly interface for operation.

[0250] Programming

[0251] Modular Control Algorithm and User Interface: To deliver a user-friendly interface and facilitate precise manipulation, it was developed a modular control algorithm with firmware sequences of modules written in C++. These modules seamlessly work together to execute commands such as moving in a specific direction, bending and orienting, and pumping air — all controlled with a simple push of a joystick knob or button.

[0252] Additionally, it was included several interface functions, empowering users to craft custom locomotion sequences, thereby expanding BIOSENTER’ s capabilities and adapting it to diverse applications.

[0253] Abstraction: Low-Level Functions: Each robotic component function generally includes intricate coordination involving the activation and deactivation of multiple valves, as well as the modulation of pump pressure levels. To streamline this process, first, low-level functions were developed as abstractions for these tasks. These functions — namely inflate _x( amt), hold_x(amt), and deflate _x( amt) where x represents one of the actuators — manage all control sequences and enable variable actuation levels as a percentage of the maximum actuation for each unit, with the input parameter amt. Additionally, the hold_x functions adjust the pumps’ maximum current limit to maintain a constant flow, stabilizing chamber pressure and quasi- statically controlling actuation . This feature is especially crucial for mitigating performance issues caused by parasitic leakage, a common challenge in pneumatic soft robotics. By serving as the foundational building blocks for the entire control system, these low-level functions facilitate seamless operation and robust performance.

[0254] Locomotion Functions: The robot includes locomotion functions such as moving straight or in a specified direction and bending to face a desired angle relative to the camera view. These functions are built upon the low-level abstraction functions and are activated via joystick commands or a preprogrammed locomotion sequence. Additionally, users can create custom functions and sequences using straightforward commands, enhancing the system's versatility and adaptability.

[0255] While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the teachings of the present invention is / are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, is included within the scope of the present invention. The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.” The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary. Thus, as a non-limiting example, a reference to “A and / or B,” when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A without B (optionally including elements other than B); in another embodiment, to B without A (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0256] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0257] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0258] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

[0259] Any terms as used herein related to shape, orientation, alignment, and / or geometric relationship of or between, for example, one or more articles, structures, forces, fields, flows, directions / trajectories, and / or subcomponents thereof and / or combinations thereof and / or any other tangible or intangible elements not listed above amenable to characterization by such terms, unless otherwise defined or indicated, shall be understood to not require absolute conformance to a mathematical definition of such term, but, rather, shall be understood to indicate conformance to the mathematical definition of such term to the extent possible for the subject matter so characterized as would be understood by one skilled in the art most closely related to such subject matter. Examples of such terms related to shape, orientation, and / or geometric relationship include, but are not limited to terms descriptive of: shape - such as, round, square, gomboc, circular / circle, rectangular / rectangle, triangular / triangle, cylindrical / cylinder, elliptical / ellipse, (n)polygonal / (n)polygon, etc.; angular orientation -such as perpendicular, orthogonal, parallel, vertical, horizontal, collinear, etc.; contour and / or trajectory - such as, plane / planar, coplanar, hemispherical, semi-hemispherical, line / linear, hyperbolic, parabolic, flat, curved, straight, arcuate, sinusoidal, tangent / tangential, etc.; direction - such as, north, south, east, west, etc.; surface and / or bulk material properties and / or spatial / temporal resolution and / or distribution - such as, smooth, reflective, transparent, clear, opaque, rigid, impermeable, uniform(ly), inert, non- wettable, insoluble, steady, invariant, constant, homogeneous, etc.; as well as many others that would be apparent to those skilled in the relevant arts. As one example, a fabricated article that would described herein as being “ square" would not require such article to have faces or sides that are perfectly planar or linear and that intersect at angles of exactly 90 degrees (indeed, such an article can only exist as a mathematical abstraction), but rather, the shape of such article should be interpreted as approximating a “ square," as defined mathematically, to an extent typically achievable and achieved for the recited fabrication technique as would be understood by those skilled in the art or as specifically described. As another example, two or more fabricated articles that would described herein as being “ aligned" would not require such articles to have faces or sides that are perfectly aligned (indeed, such an article can only exist as a mathematical abstraction), but rather, the arrangement of such articles should be interpreted as approximating “aligned,” as defined mathematically, to an extent typically achievable and achieved for the recited fabrication technique as would be understood by those skilled in the art or as specifically described.

Claims

CLAIMSWhat is claimed is:

1. A system configured to facilitate locomotion at a location internal to a subject, the system comprising:a flexible linear actuator having a first end and a second end;a first expandable actuator operably linked to the first end of the flexible linear actuator;a first sleeve adjacent the first expandable actuator, the first sleeve comprising a first patterned surface;a second expandable actuator operably linked to the second end of the flexible linear actuator; anda second sleeve adjacent the second expandable actuator, the second sleeve comprising a second patterned surface.

2. A system configured to facilitate locomotion at a location internal to a subject, the system comprising:a flexible linear actuator having a first end and a second end;a first expandable actuator operably linked to the first end of the flexible linear actuator;a second expandable actuator operably linked to the second end of the flexible linear actuator; andat least one channel extending through the flexible linear actuator, the first expandable actuator, and the second expandable actuator.

3. A system as in any preceding claim, wherein the flexible linear actuator comprises a spring.

4. A system as in claim 3, wherein the spring comprises a superelastic material.

5. A system as in any preceding claim, wherein the flexible linear actuator comprises a plurality of fibers disposed on a surface of the flexible linear actuator.

6. A system as in any preceding claim, wherein, upon expansion of the first expandable actuator, the first patterned surface comprises a plurality of protrusions.

7. A system as in any preceding claim, wherein, upon expansion of the second expandable actuator, the second patterned surface comprises a plurality of protrusions.

8. A system as in any preceding claim, comprising one or more channels disposed within the system, sized and adapted to receive one or more of a camera component, a light component, a drug delivery component, a biopsy component, a forceps component, and a fluidic component.

9. A system as in any preceding claim, comprising two or more pneumatic chambers associated with the flexible linear actuator, the first expandable actuator, and / or the second expandable actuator.

10. A system as in any preceding claim, wherein each pneumatic chamber is individually addressable.

11. A system as in any preceding claim, further comprising a controller associated with the system.

12. A system as in any preceding claim, wherein the first expandable actuator and / or the second expandable actuator comprises an expandable donut-shaped balloon.

13. A system as in any preceding claim, wherein the flexible linear actuator is configured to bend upon activation of at least one of the two or more pneumatic chambers.

14. A system as in any preceding claim, wherein the location internal to the subject is a small intestine and / or a colon of the subject.

15. A system as in any preceding claim, wherein the system is configured for endoscopic administration to the subject.

16. A system as in any preceding claim, further comprising one or more caps associated with each expandable actuator.

17. A system as in any preceding claim, wherein the first sleeve and / or the second sleeve further comprises a plurality of raster lines.

18. A system as in any preceding claim, wherein the first sleeve and / or the second sleeve comprise a Kirigami-type surface.

19. A method for locomoting an enteroscopic robot, comprising:administering to a subject, endoscopically, the enteroscopic robot, the enteroscopic robot comprising:a flexible linear actuator having a first end and a second end;a first expandable actuator operably linked to the first end of the flexible linear actuator;a first sleeve adjacent the first expandable actuator, the first sleeve comprising a first patterned surface;a second expandable actuator operably linked to the second end of the flexible linear actuator; anda second sleeve adjacent the second expandable actuator, the second sleeve comprising a second patterned surface; andlocomoting the enteroscopic robot, wherein locomoting comprises performing one or more of the following steps:expanding the first expandable actuator;extending the flexible linear actuator;expanding the second expandable actuator; deflating the first expandable actuator; shrinking the flexible linear actuator; and deflating the second expandable actuator.

Images