METHOD FOR CONVERTING INANIMATE OBJECT TO SMALL-SCALE ROBOT ON-DEMAND

Abstract

This invention provides parasitic millirobots that can effectively adapt to an unstructured environment and coherently interact with diverse objects in order to fulfil various application needs. Particularly, a minimalist millirobot construction strategy by splashing composited agglutinate magnetic spray (M-spray) is adopted, which is capable of self-turning multifarious milli-/centi-objects into parasitic millirobots on-demand. Through taking full advantage of the objects' inherent structure and a covered thin drivable film, the M-spray demonstrates superior handling (from 1-D to 3-D structures) and loading capabilities (up to thousand-fold and hundred-fold of its volume and weight, respectively) while with neglectable size increment (as low as 1%) to target. Moreover, benefitting from peculiarities of online reprogramming and controllable disintegration, the parasitic millirobots can rewrite its locomotion mode according to the task and disintegrate themselves after mission accomplished, offering high adaptivity and compatibility for in vivo biomedical applications. Methods for conversion and fabrication thereof are also provided.

Claims

1. A self-adhesive, highly viscous and wettable spray composition for fabricating one or more small-scale robots from one or more inanimate objects of one-dimensional to three-dimensional configurations on-demand, said composition comprising: one or more curable adhesive materials; and a plurality of drivable materials, the one or more curable adhesive materials, upon exposure to one or more stimuli, forming a highly viscous paste to splash in one or more splashing regions on a surface of a substrate with which the composition is in contact, and after said composition being cured, further increasing mechanical strength of the cured composition while preventing detachment of the cured composition from said substrate; the plurality of drivable materials, upon exposure to one or more stimuli and prior to curing of the composition, being aligned to have an oriented actuation direction either perpendicularly to a deformable direction of the one or more small-scale robots or in parallel to a longest planar axis of a drivable thin film formed on the substrate surface from the cured composition.

2. The composition of claim 1, wherein the one or more curable adhesive materials comprise one or more adhesive polymers to form a highly viscous polymer paste; the one or more drivable materials comprise a plurality of magnetic-responsive metal particles being aligned to have an oriented magnetization axis by magnetic field wherein a first adhesive polymer, the plurality of magnetic-responsive particles and a second adhesive polymer are in a mass ratio of 1:8:11.

3. The composition of claim 2, wherein the first adhesive polymer and the plurality of magnetic-responsive particles are doped into a solution of the second adhesive polymer at room temperature, followed by atomization into droplets for forming the drivable thin film in the one or more splashing regions on the surface of the substrate of the one or more inanimate objects.

4. The composition of claim 2, wherein the first adhesive polymer is gluten.

5. The composition of claim 2, wherein the magnetic-responsive particles are iron particles.

6. The composition of claim 2, wherein the second adhesive polymer is polyvinyl alcohol.

7. The composition of claim 1, wherein the substrate comprises polydimethylsiloxane, glass, paper, plastic, and wood, and wherein the surface of the substrate is flat, curved, or irregular.

8. The composition of claim 3, wherein the magnetic-responsive particles are aligned under exposure to an initial magnetic field such that the drivable thin film with the oriented magnetization axis is formed on the surface of the one or more inanimate objects on the substrate.

9. The composition of claim 8, wherein the initial magnetic field is in a magnitude of about 100 to 200 mT.

10. A method of fabricating one or more small-scale robots from one or more inanimate objects of one-dimensional to three-dimensional configurations on-demand, comprising: splashing the composition of claim 1 in one or more splashing regions on a surface of a substrate of the one or more inanimate objects at room temperature, wherein areas other than the splashing regions on the surface of the substrate are masked if there is more than one splashing region; applying an initial stimuli to the composition to align the one or more drivable materials to have an oriented actuation direction parallel to the direction of the applied initial stimuli; curing the composition to form the drivable thin film with an oriented actuation direction either perpendicular to a deformable direction of the one or more small-scale robots or parallel to a longest planar axis of the drivable thin film, wherein for the substrate surface with more than one splashing region the one or more small-scale robots are obtained by repeating said splashing, applying the initial stimuli to the composition, and curing the composition until all the splashing regions are cured followed by cutting the unmasked areas out from the substrate.

11. The method of claim 10, wherein the composition comprises a first adhesive polymer, the one or more drivable materials including a plurality of magnetic-responsive particles and a second adhesive polymer which are in a mass ratio of 1:8:11.

12. The method of claim 11, wherein the first adhesive polymer and the plurality of magnetic-responsive particles are doped into a solution of the second adhesive polymer at room temperature, followed by atomization into droplets for forming a thin film on the substrate of the inanimate objects.

13. The method of claim 12, wherein the first adhesive polymer is gluten.

14. The method of claim 12, wherein the magnetic-responsive particles are iron particles.

15. The method of claim 12, wherein the second adhesive polymer is polyvinyl alcohol.

16. The method of claim 10, wherein the substrate comprises polydimethylsiloxane, glass, paper, plastic, and wood, and wherein the surface of the substrate is flat, curved, or irregular.

17. The method of claim 11, wherein one of the stimuli is a magnetic field in a magnitude of about 100 to 200 mT.

18. A method for converting one or more inanimate objects into one or more three-dimensional small-scale robots on-demand in order to exert a diversity of locomotion in an unstructured environment, the method comprising: providing the one or more inanimate objects with a drivable thin film formed from the composition of claim 1 under exposure to the initial stimuli encapsulating the one or more inanimate objects.

19. The method of claim 18, further comprising: reprogramming topology order of the one or more drivable materials including a plurality of magnetic-responsive particles in the drivable thin film such that an initial oriented magnetization axis of the magnetic-responsive particles is re-aligned to a different orientation under a subsequent exposure to a second magnetic field which is stronger than the first magnetic field; and magnetically disintegrating the drivable thin film from the one or more small-scale robots under exposure to an oscillating magnetic field, wherein said second magnetic field is about 200 mT or more, and is applied in a direction perpendicular to that of the initial magnetic field during formation of the drivable thin film, and wherein said topology order of the plurality of the magnetic-responsive particles is reprogrammed by wetting the drivable thin film so that spacing between each of the plurality of magnetic-responsive particles in the drivable thin film increases before being exposed to the second magnetic field.

20. The method of claim 19, wherein said oscillating magnetic field applied to the one or more small-scale robots has an oscillating frequency of about 1 to 3 Hz in a magnitude of about 10 mT for about 2 to 4 minutes.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Embodiments of the invention are described in more details hereinafter with reference to the drawings, in which:

[0042] FIG. 1A schematically depicts the M-spray turns an origami crane into a magnetic millirobot according to an embodiment of the present invention;

[0043] FIG. 1B shows a coating of the present M-spray from a pressurization watering can;

[0044] FIG. 1C illustrates the adhesion process of the M-spray droplets on PDMS and glass surface by a series of photographs; droplets adhere to the substrate stably and firmly without bounce or lateral migration;

[0045] FIG. 1D shows a surface texture of the M-skin before and after alignment and curing;

[0046] FIG. 1E shows magnetic susceptibility of the cured M-skin with 40% mass fraction of MPs when the applied magnetic field strength is from 0 to 200 mT;

[0047] FIG. 1F shows magnetic susceptibility of the cured M-skin corresponding to various MP content from 30 to 50 wt. % under 100 mT; error bars indicate the SD for n=4 measurements at each data point;

[0048] FIG. 2A schematically depicts the state change of the M-spray between viscous and nonviscous forms;

[0049] FIG. 2B schematically depicts the bonding force between cured M-skin and substrate surface during the peeling process;

[0050] FIG. 2C shows a series of optical microscopy images of the contact surface on testing materials after the M-skin is peeled off;

[0051] FIG. 2D shows quantitative peeling strength of the M-skin to rough (paper and wood) and smooth surfaces (PDMS, glass, and plastic); error bars indicate the SD for n=5 measurements at each data point;

[0052] FIG. 2E shows the curing rate of the M-spray at different environment temperatures;

[0053] FIG. 2F shows the effect of magnetic particles (MP) content and PVA solution concentration on the final thickness of the M-skin; error bars indicate the SD for n=10;

[0054] FIG. 3A schematically depicts the enlarged part of the robot's single anchor for general mechanical analysis;

[0055] FIG. 3B schematically depicts diverse millirobots from inanimate objects by M-spray coating of the present invention with negligible size variant, including soft cotton rope (line), origami (plane), PDMS film (curve), and plastic pipe (round). mg is the gravity, and F.sub.N, Ff, F.sub.M are the supporting force, friction force, and magnetic force, respectively;

[0056] FIG. 3C shows three comparison curves that the deformation and the locomotion of M-skin millirobots are regulated by the strength and the direction of magnetic field and the substrate's material property and inherent structure; error bars indicate the SD for n=3;

[0057] FIG. 4A shows a series of fluorescent photos for the swelling of the present M-skin under wetting;

[0058] FIG. 4B depicts the reprogramming of cured M-skin's easy magnetization axis from horizontal to vertical under wetting and a 200-mT magnetic field, during which the demonstrated sample with a MP content of 1% shows the reorganization process;

[0059] FIG. 4C shows the direction changing state of easy magnetization axis and the corresponding applied magnetic field and reprogramming time according to an embodiment of the present invention;

[0060] FIG. 4D schematically depicts the quantitative magnetization measurement of M-skin before and after reprogramming, where the tested sample with a MP content of 40% and a size of 5 mm by 5 mm was reprogrammed under 200 mT within 10 min;

[0061] FIG. 4E shows the three-section reptile robot demonstrates caterpillar (3D) and concertina (2D) motion before and after reprogramming without structure changing;

[0062] FIG. 4F shows the deformation of robot during 3D caterpillar and 2D concertina motion, respectively;

[0063] FIG. 4G shows the step size comparison between caterpillar (3D) and concertina (2D) motion under the same magnetic field strength with a frequency of 1 Hz;

[0064] FIG. 4H shows robot height variation as time changes during caterpillar (3D) and concertina (2D) motion;

[0065] FIG. 5A schematically depicts the oscillation magnetic-induced disintegration of M-skin in aquatic environment;

[0066] FIG. 5B shows free M-skin disintegration rate over time, where the size of cured M-skin is 5 mm by 5 mm under a 10-mT oscillating magnetic field with a frequency from 0 to 5 Hz; error bars indicate the SD for n=3;

[0067] FIG. 5C shows M-skin disintegration rate over time on different materials' surfaces under the oscillating magnetic field with a strength of 10 mT and a frequency of 1 Hz; error bars indicate the SD for n=3;

[0068] FIG. 5D is a series of photographs depicting the shedding and disintegration process of M-skin from a multi-foot origami robot;

[0069] FIG. 5E shows different disintegration rates of M-skin over time when the gluten content changes from 0 to 10%; error bars indicate the SD for n=3;

[0070] FIG. 5F shows the changes in swelling time of M-skin against the environmental pH changes from 1 to 13; error bars indicate the SD for n=3;

[0071] FIG. 5G shows M-skin disintegration rates over time under the same oscillating magnetic field (10 mT, 1 Hz) and diverse environmental pH (from 1 to 13); error bars indicate the SD for n=3;

[0072] FIG. 6A schematically depicts active steering catheter constructed by M-spray coating and its deformation model under magnetic fields with different strengths;

[0073] FIG. 6B schematically depicts the navigation ability of the one-point catheter in a narrow vascular model;

[0074] FIG. 6C schematically depicts the reprogramming of multi-point sampling cotton thread for various sets of active steering catheter;

[0075] FIG. 6D shows reprogramming of the easy magnetization axis of multi-point sampling cotton thread according to the corner angle of the throat, which can achieve the fast directional steering under the actuation of magnetic torque and can reduce the risk of extrusion with throat wall during insertion;

[0076] FIG. 6E schematically depicts the construction of an adaptive drug capsule millirobot and its multiple locomotion modes as well as controllable disintegration;

[0077] FIG. 6F shows controllable locomotion and disintegration of an as-fabricated M-skin capsule for active delivery in an ex vivo animal model;

[0078] FIG. 7A schematically depicts an example of using the present invention for drug delivery in rabbit stomach, where the magnetic field is applied for robot actuation; radiology imaging is adopted for locomotion evaluation; and ultrasound imaging is adopted for drug release evaluation;

[0079] FIG. 7B shows a series of radiology images of an M-skin capsule according to an embodiment of the present invention steered in a stomach with a controllable O trajectory;

[0080] FIG. 7C shows ultrasound images for an in vivo evaluation of bead diffusion, where the distribution of beads released from the capsule in the rabbit stomach is sparse with limited detection in control group 1, whereas the bright region on the stomach wall in experiment group 1 indicates that the M-skin capsule can concentrate bead release on the targeted region;

[0081] FIG. 7D shows optical images for the retention of biological stain in control group 2 (left) and experiment group 2 (right)

[0082] FIG. 8 shows the comparison of adhesion property between water droplet and M-spray droplet;

[0083] FIG. 9 shows the curing process and magnetic property of M-spray and the equipment used for magnetic field production;

[0084] FIG. 10 shows the actuating performance of the M-skin under magnetic field;

[0085] FIG. 11 shows the mechanical properties and adhesiveness of the cured M-spray;

[0086] FIG. 12 shows the design and locomotion analysis of diverse M-skin millirobots;

[0087] FIG. 13 shows the construction process of M-skin millirobots;

[0088] FIG. 14 show the actuation of M-skin millirobots by permanent magnet;

[0089] FIG. 15 shows locomotion demonstration of the constructed M-skin millirobots;

[0090] FIG. 16 shows the performance evaluation of different motion modes on diverse surfaces;

[0091] FIG. 17 shows the environment adaptability and obstacle overcoming ability of diverse M-skin millirobots;

[0092] FIG. 18 shows the constructed M-skin millirobots work in both land and liquid environment;

[0093] FIG. 19 shows the controllable magnetic-induced disintegration of M-skin in aquatic environment;

[0094] FIG. 20 depicts the process that M-skin detaches after task completing from target inanimate objects;

[0095] FIG. 21 shows the disintegration of M-skin with different material components in strong acid environment (pH 1) without magnetic oscillation;

[0096] FIG. 22 shows the influence of physiological blood flow on the locomotion speed and disintegration process of M-skin catheter.

DETAILED DESCRIPTION OF THE INVENTION

[0097] In the following description, systems and methods for and the likes are set forth as preferred examples. It will be apparent to those skilled in the art that modifications, including additions and/or substitutions may be made without departing from the scope and spirit of the invention. Specific details may be omitted so as not to obscure the invention; however, the disclosure is written to enable one skilled in the art to practice the teachings herein without undue experimentation.

[0098] It should be apparent to practitioner skilled in the art that the foregoing examples of the system and method are only for the purposes of illustration of working principle of the present invention. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed.

[0099] Raw Materials of M-Spray

[0100] The PVA with 87.0 to 89.0% degree of alcoholysis was bought from Aladdin Chemistry Co. Ltd. Gluten (wheat protein) was obtained from Mingzuotang fishing tackle Corporation. Iron micropowder [Spherical, aerodynamic particle sizer (APS) 6 to 10 μm, reduced, 99.5%] was purchased from Alfa Aesar. Water with a resistivity of 18.2 megohms.Math.cm at 25° C. was acquired from a Millipore Milli-Q system and was used for all solution preparations. The 10 wt % PVA solution was prepared under stirring at 500 rpm for 2 hours under 90° C. with a magnetic stirrer (RCT basic, German IKA Corporation). All chemicals with the purity of analytical reagent grade were used as received without further purification.

Preparation of Agglutinate M-Spray Composition and Characterization

[0101] The raw material for M-spray was composited by mixing or doping gluten and magnetic particles (MPs) with a 10 weight % (wt %) PVA solution in a mass ratio of 1:8:11 at room temperature. Then, the composited material was atomized into droplets and coated on the surface of target object at a speed of ˜1 m/s, and a thin colloidal-like film (˜500 μm) was formed as the merging of droplets in a few seconds (FIG. 1B). As illustrated in FIG. 1C, the M-spray droplet could adhere to the substrates immediately. Furthermore, no spray recoil was observed, which was distinct from what was observed with a water droplet (FIG. 8A). Moreover, after the M-spray landed on the substrate, the radius of the contact area r continuously increased or remained stable but never decreased due to its high agglutination and viscosity. For instance, the contact area of M-spray droplet remained stable on the hydrophobic PDMS surface and increased 56% in ˜1 s on the hydrophilic glass surface (FIG. 1C). To further evaluate the wetting ability of M-spray, control experiments on different substrates including PDMS, glass, paper, plastic, and wood, were conducted for several times (FIG. 8B). The results indicated that the M-spray can achieve a similar contact angle as a water droplet on the hydrophilic surface and a smaller contact angle on the hydrophobic surface, suggesting its high wetting ability to diverse materials. The attributes of high agglutination and viscosity (˜550 mPa.Math.s), as well as wetting ability, made the M-spray stick on various surfaces stably and firmly, which ensures effective adhesion-based robotization of the inanimate targets.

[0102] Self-adhesive ability of the M-spray is endowed by the component of PVA and gluten. As illustrated in FIG. 2A, before curing, the hydroxyl groups in the molecular chain of PVA combine with water molecules, leading to strong hydrogen bonds (˜CH.sub.2—CH—OH . . . H—O—H . . . HO—CH—CH.sub.2˜) and a form of highly viscous polymer paste. When the paste fills the gap and fully contacts with the surface of a target object, they adhere together by van der Waals force (23). On the contrary, after the M-spray is cured to a thin film, or called M-skin, i.e., the liquid state of M-spray is converted into a solid form, where the strong hydrogen bonds between PVA chains and water are replaced by the weak hydrogen bonds between PVA chains during the conversion (24). Meanwhile, the van der Waals force between the cured M-spray and other objects becomes negligible due to a poor contact area at the rigid form. As a result, the M-skin can stably adhere to the target object and remain non-viscous to other objects after curing. Specifically, for objects with a rough surface, the generated paste can diffuse into the micropores and remain as a residue when peeling off, where the adhesion will be enhanced by the hydrogen bonds between the molecular chains of PVA during material tearing (FIGS. 2B and 2C). In the above process, gluten plays two notable roles in making the cured M-skin reliable: one is to enhance the mechanical property of the structure (FIG. 11B), and the other is to increase the adhesive ability (25) on the substrate with a rough surface (FIG. 11D). Compared with PVA, the molecular chain of gluten can form a tight network when absorbing water, allowing the cured M-skin to maintain a strong skeleton. However, it is worth noting that addition of gluten is not unlimited because a larger ration of gluten will increase the chance of agglomeration in the M-spray atomization and eventually result in failure fabrication. In one embodiment, gluten at 5% content is chosen according to various test results described hereinafter.

[0103] To further demonstrate the adhesive ability of the M-spray, the M-spray was applied between two paper belts (contact area, 5 mm by 5 mm) and then separated them at a constant speed of ˜1 mm/s (FIG. 11E). The experimental result indicates that the M-spray is able to bond the paper belts together with an adhesion strength of ˜0.17 N/mm.sup.2 after curing. This value is about 125% of the value obtained with carbon conductive double-faced adhesive tapes (731, carbon tape, 5 mm in diameter, Nisshin EM Co. Ltd.) under the same experimental conditions. As shown in the quantitative peeling-off results presented in FIG. 2D, the average peeling strength of M-spray to different tested materials ranged from 2.8 to 117.2 N/m by case. The adhesion strength to the rough surface is dozens of times stronger than that to the smooth surface, which is mainly caused by the larger bonding force of hydrogen bonds than the van der Waals force as discussed above.

[0104] To further understand the paste-solid transition of M-spray, the effects of temperature, MP content, and PVA solution concentration on the curing process were studied by contrast experiments. FIG. 2E presents the weight change of the M-spray with 40% MP content in the curing process, indicating that higher temperature would greatly speed up the paste-solid transition process. In FIG. 2E, the transition time was shortened from ˜30 min at 30° C. to ˜5 min at 70° C. due to the faster water evaporation. It is found that the final structure and size of the M-skin is not relevant to the curing speed, suggesting that a faster on-demand construction is achievable by accelerating the paste-solid transition, such as higher temperature, lower humidity, or enhanced air convection. On the other hand, the thickness of M-skin is found to be relevant to the MP content and PVA solution concentration (FIG. 2F). Particularly, it decreased nearly threefold (from 251 to 94 μm) when the MP content decreases from 50 to 30% and the PVA solution concentration was adjusted from 15 to 5%, which could provide guidance for adjusting the M-skin's thickness.

[0105] The Magnetization Characterization of M-Skin

[0106] To endow the controllable actuation, the random MPs in the agglutinate M-spray composition were aligned into orientated chains by applying a −100-mT directional magnetic field, in which the formed magnetic chains tend to coincide with the magnetic field lines. After thermal curing, a thinner, solidified magnetic film (˜100 to 250 μm) with an oriented easy magnetization axis was obtained on the surface of the inanimate object in several minutes, namely magnetic skin, or M-skin for short (FIG. 1D and FIG. 9).

[0107] To quantitively evaluate the magnetization (magnetic moment density) of M-skin under different magnetic field strengths and MP mass fractions, the M-skin in a dimension of 10 mm by 10 mm by 0.2 mm was peeled off from the substrate carefully and its magnetization was measured by a vibrating sample magnetometer (DMS 1660, ADE Technologies) (FIGS. 1E and 1F). The results indicate that the M-skin with 40% MPs mass fraction exhibited a nearly linear increase in magnetization from 0 to 166.1 kA/m with an increase in the applied magnetic field from 0 to 200 mT (FIG. 1E). In addition, the magnetization also almost linearly increased from 72.2 to 154.9 kA/m corresponding to the increment of MP mass fraction from 30 to 50% while keeping the applied magnetic field at about 100 mT (FIG. 1F). This directional and controllable actuating capability of M-skin (FIG. 10) made it possible to turn inanimate objects into magnetic millirobots.

The Peeling Strength Test of M-Spray to Different Materials

[0108] The combining force between the M-spray and inanimate objects was evaluated by the peeling strength. In the test, the M-spray was daubed as a strip (25 mm by 50 mm) on the surface of different testing objects, including standard A4 paper (Double A, premium), wood (Cedar), PDMS (0.1 equivalent curing agents, Sylgard 184, Dow Corning), glass slide (catalog no. 7107, Sail brand), and plastic sheet (polyethylene). After the evaporation of excess water, the cured M-spray was peeled off along the long axis direction at a constant speed of 2.5 mm/s. The dynamometer (ELK-20, 0.01 N precision, Elecall Corporation) was used to obtain the average force during the peeling process.

The Fabrication Process of the M-Skin Millirobots

[0109] In general, the fabrication of the M-skin millirobot followed the same coating, magnetizing, and curing process. For a fully coated walking robot (FIG. 13A), the M-spray was first coated on a curved PDMS film and then stretched it to a plane and magnetized at about 100 mT along the long axis during the curing process. After curing, the walking robot was obtained by recovering the PDMS film to curve. For the soft reptile robot and rolling robot, which were partly coated (FIGS. 13C and 13D), a mask was used to protect the unselected region before coating M-spray. Then, the magnetic field with a strength of 100 mT was adopted to magnetize the robot with a single magnetization direction during curing. Last, the designed reptile robot and rolling robot could be obtained after curing.

[0110] The multi-foot origami robot (FIG. 13B) was constructed with multiple partial coats and with multiple magnetization directions. First, the designed pattern was printed on the paper as the substrate of the constructed origami robot. Second, the mask with a designed penetrable area was used to select the first coating region. After the spraying, magnetizing, and curing, the first coating region was obtained. Then, other regions with the mask were selected and the spraying, the magnetizing, and curing were repeated. Last, the magnetic multi-foot origami robot was obtained by cutting and folding the substrate.

Disintegration Evaluation of M-Skin

[0111] The cured M-skin in still water could maintain stability but become disintegrable after applying magnetic agitation generated by the Helmholtz coil system. Here, the disintegration rate was defined as the ratio between the area of fragmentation and the original area of M-skin. Fragmentations with a size smaller than 2.5% of the origin area were considered as disintegrated. For the disintegration analysis of free M-skin, the size of M-skin was 5 mm by 5 mm, and the applied magnetic field had a strength of 10 mT and frequency from 0 to 5 Hz. To investigate the influences of different substrate surfaces on the M-skin disintegration, the M-spray with the same size of 5 mm by 5 mm was daubed to the different material substrates (table 1) under an applied magnetic field with a strength of 10 mT and a frequency of 1 Hz.

TABLE-US-00001 TABLE 1 Substrates used in the M-skin disintegration testing: Materials Size (mm.sup.3) Weight (g) Remarks Wood 10 × 10 × 5.0 0.4643 Cedar Paper 10 × 10 × 0.1 0.0085 A4 paper PDMS 10 × 10 × 0.7 0.0632 0.1 equivalent curing agents Glass 10 × 10 × 1.0 0.2681 CAT. NO. 7107, Sail brand Plastic 10 × 10 × 0.3 0.0323 Polyethylene

In Vivo Model Setup

[0112] This test aims to collect basic evidence for drug delivery function of the proposed millirobot in live animals. Four 8- to 12-week-old male New Zealand rabbits, weighing 1.8 to 2.1 kg, were obtained from Shenzhen Advanced Medical Services Co. Ltd. and randomly divided into four groups. No animal was excluded from this study. All rabbits underwent 8 hours of fasting treatment before the experiment. Both water feeding and anesthesia were maintained during the whole experiment process. Experiment group 1 was treated by oral administration of the constructed M-skin capsules containing 1.0-g glass bead particles (500 μm), and the same glass beads without M-skin capsules were orally delivered to control group 1. Experiment 2 was treated by the constructed M-skin capsules containing 0.05-g biological stain (Indigo carmine, Phygene Scientific, PH9195), and control group 2 was given the same amount of stain without M-skin capsules by oral delivery. The locomotion of M-skin capsule was achieved by magnetic field, and its position was detected by radiology imaging (DSA, CGO-2100, Wandong). Because of the harmfulness of radiology imaging, the magnetic actuation and imaging were conducted at intervals. After half an hour, the retention of glass beads in vivo (control group 1 and experiment group 1) was evaluated by ultrasound imaging (Philips EPIQ 7 ultrasound system), and the diffusion of biological stain (control group 2 and experiment group 2) was observed by collecting the stomachs after euthanasia.

Principle of Turning Inanimate Objects Into Millirobots

[0113] The roboticization of inanimate objects is realized by the directional magnetization of M-skin and the controllable actuation magnetic field. For an inanimate object with a soft or deformable structure, an easy magnetization axis of M-skin perpendicularly to the deformation direction was oriented to achieve a repeatable morphological change (FIG. 12A). On the other hand, for a rigid or nondeformable inanimate object, the easy magnetization axis of M-skin was aligned in parallel to its long axis for holistic locomotion, such as slipping, flipping, and rolling (FIG. 12B). Theoretically, given a constructed M-skin millirobot with an arbitrary structure, it can be modeled as M parts and N contact lines (or points) with the ground. When the magnetic field is applied or removed away, the motion of the ith single anchor is reliable if the criterion meets:

F.sub.fn+.sup.i+1.sub.iF.sub.x−.sup.i−1.sub.iF.sub.x+.sup.i−1.sub.iF.sub.z+m.sub.ig−.sup.i+1.sub.iF.sub.z−F.sub.Nn−F.sub.zi=m.sub.ia≠0; or

T.sub.yi+.sup.i−1.sub.iT.sub.y−.sup.i+1.sub.iT.sub.y−(μsin θ.sub.i−cos θ.sub.i)F.sub.Nnr.sub.i=J{umlaut over (θ)}.sub.i≠0,

where r.sub.i(i=1, . . . , M) is the distance between contact line c.sub.n and mass center m.sub.i of the i.sub.th part of robot, μ is friction coefficient, θ.sub.i is the angle between line c.sub.n-m.sub.i and horizontal direction, F.sub.Nn,F.sub.fn are supporting force and friction force from the ground, and T.sub.yiF.sub.xi, F.sub.zi are magnetic moment and pulling forces along Y axis, X axis, Z axis, respectively. .sup.i−1.sub.iT.sub.y, .sup.i−1.sub.iF.sub.x, .sup.i−1.sub.iF.sub.z are explaining equivalent moment to m.sub.i and forces exerted by m.sub.i−1 part, and .sup.i+1.sub.iT.sub.y, .sup.i+1.sub.iF.sub.x, .sup.i+1.sub.iF.sub.z are equivalent moment to m.sub.i and forces exerted by m.sub.i+1 part, respectively (FIG. 3A). In other words, when existing at least one value i that satisfies the above criterions, the designed parasitic millirobot will respond to the magnetic field, i.e., a.sub.i≠0 indicates translation and {umlaut over (θ)}.sub.i≠0 indicates swing or rotation.

[0114] To explain the above model and exhibit the versatility of M-spray in turning diverse objects into millirobots, FIG. 3B depicts the process of converting cotton rope (line), origami (flat), PDMS (curve), and plastic pipe (round) into soft reptile robot, multiple-joint robot, walking robot, and rolling robot, respectively (26, 27). The fabrication of these millirobots follows the similar coating, magnetization, and curing process as the M-skin, except for peeling off. Specifically, for the robot with more than one coating area, such as the multi-foot origami robot, a mask is used to protect the unselected region and guarantee accuracy. The detailed fabrication process of these robots is given in Materials and Methods and illustrated in FIG. 13. The actuation of these millirobots is realized by a portable permanent magnet (50 mm by 50 mm by 25 mm) underneath (40 mm), which could generate a magnetic field with a strength of ˜50 mT and a gradient of ˜1000 mT/m. For the deformable soft reptile robot, the applied swing magnetic field is generated by the reciprocating motion of permanent magnet in the xy plane. With the cooperation of the magnetic pulling force, the constructed reptile robot can creep forward by sliding its two con-tact points alternately (FIGS. 12C, 14A, and 15A). For the multi-foot origami robot, the permanent magnet moves up and down in the xz plane to achieve curling and stretching of the robot; by repeating, the robot can crawl like a multi-foot insect (FIGS. 12D, 14B, and 15B). For the walking robot, the permanent magnet moves in the xz plane with an O trajectory, moving the robot forward in an inchworm-like locomotion style (FIGS. 12E, 14C, and 15C). For the nondeformable plastic pipe, the magnetic force provides the power for rolling, and the magnetic torque steers the rolling direction (FIGS. 12F, 14D, and 15D). These results indicate that diverse millirobots can be constructed with different attributes just by following the similar standardized M-spray adhesion process, offering an effective on-demand millirobot construction strategy to fulfill tasks with different environments, surface conditions, and obstacles. More detailed locomotion demonstration, modeling, and analysis of each millirobot are given in Supplementary Text (FIGS. 16 and 17, table 2).

TABLE-US-00002 TABLE 2 The performance evaluation summary of different motion modes under diverse surface conditions: Motion performance evaluation Locomotion mode Glass Ice Skin Wood Sand Reptile crawling Medium Medium Good Medium Medium Multi-foot crawling Medium Medium Good Good Good Curved-film Good Good Medium Medium Poor walking Pipe rolling Medium Poor Good Good Good Stick slipping Medium Medium Medium Poor Poor Capsule flipping Medium Medium Good Good Good

[0115] The strategy of turning inanimate objects into M-skin millirobots fully uses the structure of the objects, leading to several advantages in adaptivity, miniaturization, and efficiency. As the comparison curves show in FIG. 3C, the deformation and locomotion of M-skin millirobot are regulated by the strength and direction of magnetic field, the objects' material property, and inherent structure. Due to the efficient utilization of the target structure, an inanimate target can be actuated by using a small amount of M-spray with a negligible size increment to the object, which can be as low as 1 per mil in volume. Moreover, because most of the applied magnetic energy contributes to the actuation of the target and very little energy is needed to maintain the M-skin itself, the proposed M-spray has an ultrahigh transportation ability of up to several hundred times its own weight. For instance, 0.01 g of M-spray (after curing) can drive a bulk plastic tube with a weight of 3.63 g under normal-level magnetic field (strength, ˜50 mT and gradient, ˜1000 mT/m), which is ˜360 times its own weight and ˜1600 times its own volume (FIG. 15D). The advantages of M-skin millirobot in high adaptability, negligible size variation, and high working efficiency offer a unique strategy for robot-object interaction at small scales, especially for tasks with limited space.

[0116] In practice, the reprogramming of the easy magnetization axis in the M-skin with 40% MP mass friction can always be ensured in 5 min as long as the magnetic field strength is sufficient, i.e., larger than 200 mT, based on our experiment trials (FIG. 4C). The results also indicate that the reprogramming efficiency is positively proportional to the applied magnetic field strength. For instance, it takes ˜5 min to reprogram the direction of easy magnetization axis from horizontal to vertical under a 200-mT magnetic field, and this process is extended to ˜17 min under a 100-mT magnetic field. Note that the magnetic field for actuation (˜50 mT) is much lower than the strength for easy magnetization axis reprogramming (200 mT); thereby, the robot constructed by M-skin can keep stable and locomote effectively at the wet or liquid environment, as evidenced by the jellyfish robot in FIG. 18. To quantitatively evaluate the efficiency and stability of the easy magnetization axis after realignment, contrast tests were performed to measure the magnetization of M-skin before and after reprogramming. As shown in FIG. 4D, after reprogramming under a 200-mT magnetic field for 10 min, the magnetization of all the three M-skins exhibited a small discrepancy (13.0, 6.8, and 9.2 kA/m under 200 mT) compared with their initial states, i.e., discrepancy of 7.7, 3.9, and 5.4% for samples 1, 2, and 3, respectively. These results suggest that the proposed reprogramming strategy is feasible and repeatable for rearranging the easy magnetization axis of M-skin.

[0117] The on-demand reprogramming ability endows an M-skin millirobot with high adaptivity to achieve diverse locomotion. To demonstrate this, a simple reptile millirobot (28) was constructed by coating M-spray on three sections of a plastic belt (FIG. 4E). Initially, the easy magnetization axes of these three M-skins are aligned along the horizontal. When a swing magnetic field is applied, the M-skins will tilt up or down, and the robot crawls forward by alternating the front anchor and rear anchor like a caterpillar. On the other hand, after the easy magnetization axes are reprogrammed along the diagonal, the millirobot can shrink to an “S” form under a horizontal magnetic field and restore when removing the magnetic field. By repeatedly applying and withdrawing the magnetic field, the millirobot deforms like a concertina to move forward by alternating anchors. Further quantitative analyses reveal that the millirobot with the same structure can exhibit essentially different locomotion styles in deformation angle (FIG. 4F), step size (FIG. 4G), and height variation (FIG. 4H) by reprogramming. Benefiting from the on- demand reprogramming ability, the M-skin millirobot can switch its motion between 3D caterpillar and 2D concertina to adapt to different environments, such as moving with a high speed by cater- pillar motion (˜10-fold faster than concertina motion) at free space and clinging to the ground by concertina motion for crossing a narrow crevice (interval, ˜2 mm) (FIG. 4E). More details about the locomotion analysis can be found in Supplementary Text.

Magnetic-Induced Disintegration

[0118] The cured M-skin has good stability in still water or under a static magnetic field due to the low solubility of PVA at normal temperature (FIG. 19A), which means that an M-skin millirobot can remain stable in an aqueous environment. However, it can be controllably disintegrated by increasing the kinetic energy of MPs to overcome the inner constraints via applying an oscillating magnetic field in an aqueous environment (FIG. 5A and FIG. 19B). As shown in FIG. 5B, the disintegrated speed of M-skin is positively proportional to oscillating frequency f from 0 to 3 Hz, and the disintegration can be completed within 4 min under a 10-mT magnetic field with a frequency of 1 Hz. It is noted that the disintegration time will take several-fold longer after M-skin adheres to objects because the joint surface can enhance its structural integrity (FIG. 5C and FIG. 20). The optical images in FIG. 5D display the shedding and disintegration of M-skin from the multi-foot origami robot under the aqueous environment, where a 10-mT oscillation magnetic field with a frequency of 1 Hz was applied. Although the existing millirobot provides opportunities for effective cargo transportation, the postprocessing of the robot after task remains a big challenge, which may still cause unpredicted side effects. Magnetic-induced disintegration ensures that the constructed M-skin millirobot can disintegrate on command (FIGS. 18C and 20C), making it suitable for controllable cargo unloading. Moreover, the component of MPs is pure Fe in our M-skin design. As a natural metal (ferritin) in the human body, the side effect from its disintegration is negligible (29), making it a good candidate for biomedical applications.

[0119] To further understand the disintegration process, the effect of mass fraction and pH value on the disintegration speed was evaluated. Because gluten can enhance the mechanical property of an M-skin and PVA can endow an M-skin with better film-forming ability and adhesiveness, both a lower mass fraction of gluten and a lower concentration of PVA solution will accelerate disintegration (FIG. 5E and FIG. 19C). For instance, an M-skin without gluten can be disintegrated completely under the magnetic oscillation within 2 min, whereas an M-skin with 10% gluten can remain more than half intact after 4 min under disintegration conditions. Similarly, the M-skin adopting a 10% PVA solution concentration can be disintegrated in about 4 min, whereas the one adopting a 20% concentration of PVA solution disintegrated 20% in the same time. However, it is worth noting that the mass fraction of gluten and the concentration of PVA solution should be kept in a proper value when in use, i.e., PVA solution concentration of ˜10% and gluten of ˜5%, by weighing the fabrication, adhesiveness, actuation, and reliability of M-skin.

[0120] Regarding the effect of pH value, the swelling and disintegrating process of M-skin are accelerated when the acidity is enhanced because the weak hydrogen bonds between PVA chains will be replaced by the strong hydrogen bonds between PVA chains and hydrogen ions (FIGS. 5F and 5G, and tables 3 and 4). Specifically, the M-skin will start to disintegrate in about 8 min under the strong acid environment (pH 1) even without magnetic oscillation, caused by the chemical reaction between iron particles inside the M-skin and the hydrogen ions inside the acid (FIG. 21, A and B). To prolong the effective working time of M-skin in the strong acid environment, two kinds of improvements can be adopted: one is to coat an additional PVA layer on the surface of M-skin after curing; the other is to change the MPs into other contents that do not react with the hydrogen ions inside the acid, such as nickel. As shown in FIG. 21 (C and D), the additional PVA covering can extend the disintegration without magnetic oscillation from ˜8 to ˜15 min, whereas the M-skin with nickel particles can keep stable in the strong acid environment even after 30 min.

TABLE-US-00003 TABLE 3 The swelling and disintegration of M-skin without magnetic oscillation under different environmental temperature and pH: Temperature Time (s) (° C.) State pH 1 pH 4 pH 7 pH 10 pH 13 Room Full Swelling 320 ± 26 394 ± 48 431 ± 52 485 ± 33 666 ± 50 Temperature Disintegration 1480 ± 83  4480 ± 703 6260 ± 600 8700 ± 950 Never (20° C.) Body Full Swelling 148 ± 18 311 ± 31 376 ± 36 422 ± 36 467 ± 43 Temperature Disintegration 620 ± 91 3040 ± 682 4820 ± 330 6386 ± 388 10400 ± 916 (37° C.)

TABLE-US-00004 TABLE 4 The swelling and disintegration time of cured film composed of different materials without magnetic oscillation: Material Time (s) Composition State pH 1 pH 4 pH 7 pH 10 pH 13 PVA Solution Full Swelling 168 ± 39 256 ± 50 350 ± 38 416 ± 85 477 ± 48 Disintegration 3500 ± 641 4486 ± 280  5386 ± 1120  7560 ± 1101 Never 40% Fe in PVA Full Swelling  93 ± 20 199 ± 50 266 ± 44 315 ± 33 358 ± 13 Solution Disintegration  760 ± 124 3040 ± 307 4300 ± 283 5780 ± 510 Never 40% Fe and 10% Full Swelling 320 ± 26 394 ± 48 431 ± 52 485 ± 33 666 ± 50 gluten in PVA Disintegration 1480 ± 183 4480 ± 703 6260 ± 600 8700 ± 950 Never Solution

M-Skin-Covered Catheter For On-Demand Active Navigating

[0121] The catheter is a widely used tool to treat diseases or to perform surgical procedures in the body cavity, duct, or vessel. Because of its thin and flexible structure, the insertion is usually conducted passively, and the corner crossing is very challenging in practice. Here, an M-skin catheter was constructed with active steering and navigating abilities by coating M-spray (thickness, ˜150 μm; length, 8 mm) on the existing flexible catheter head end (diameter, 1 mm) followed by an axial magnetization (FIG. 6A). In this design, the M-spray mainly plays two functions: One is to provide the magnetic force F to pull the flexible wire forward, and the other is to steer the course by magnetic torque T. Same as existing magnetic steering catheters (30-32), the bending radius r and degree θ of the tip depend on the ratio of flexible length L.sub.Flex and stiff length L.sub.Stiff, as well as the strength and direction of applied magnetic field. By leveraging an appropriate constraint and magnetic field, the constructed M-skin catheter can perform sharp or smooth turns.

[0122] To demonstrate the active guidance ability of the M-skin catheter, the thrombus in a narrow blood vessel model (minimum diameter, 4 mm and maximum diameter, 9 mm) with a 120° branch corner was targeted. As illustrated in FIG. 6B, the con-structed M-skin catheter first moves forward ˜45 mm to the fork of blood vessels in 20 s by manual feeding and magnetic pulling. After that, magnetic torque was steered to a direction by rotating 60° clockwise in order to make the catheter turn right about 60° into the target branch. Last, the catheter transports forward ˜30 mm in 60 s to approach the target. Considering the blood flow in practical vessels, the motion ability and stability of an M- skin catheter were studied under the effects of liquid flow. First, the impact of still blood itself on the disintegration is negligible, and the M-skin of the catheter can keep stable even after 2 hours (FIG. 22A). The moving speed of catheter decreased as the liquid flow velocity increased (FIG. 22D), but the influence of the blood flow on locomotion would not be a major issue because manual wire feeding is always used in clinical applications. For disintegration without the oscillating magnetic field, the M-skin was stable for 50 to 20 min as the liquid flow velocity changed from 50 to 200 mm/s (FIG. 22E), which is an acceptable value to meet the requirement of many clinical application cases.

[0123] Benefiting from the features of on-demand fabrication and reprogramming, our method can also set more than one coating region to construct the multi-point M-skin catheter flexibly. Different from the conventional magnetic steering catheter whose turning radius depends on the length of flexible section and the constraints from inner walls of working space, the multi-point M-skin catheter can achieve various sets of steering by programming the easy magnetization axis of each coating section (FIG. 6C), leading to higher adaptability in implementing tasks in harsh environments. Taking a multi-point M-skin sampling cotton thread as an example (Supplementary Text), to better fit the irregular corner structure of a throat with sharp turn of ˜90° and a narrow radius of ˜10 mm, the thread was reprogrammed accordingly to angles of 90°, 30°, and 0° for the three sections, respectively. As the results show in FIG. 6D, the target-based reprogrammed cotton thread can achieve the fast directional steering under the action of magnetic torque and can reduce the risk of extrusion with throat wall during insertion as well. The ability to quickly set the desired orientation and designed configuration without changing the main structure of the catheter offers promising potentials for catheter manipulation in the complex esophagus, vessel, and urethra, where navigation is always required.

M-Skin-Covered Capsule For Active Delivery

[0124] An active drug delivery system demonstrates many advantages in disease treatment over traditional pills because of its higher local drug concentration and enhanced retention in the gastric mucous layer (33). Effective transportation of cargo containing drugs in multiple environments (dry, wet, flat, and pleated surface) would promote clinical applications. For instance, the stomach is relatively “dry” when empty but will become “wet” when full of food, water, and gastric juice. Moreover, if the lesion (e.g., stomach ulcer) is at the top of the stomach where liquid media cannot reach it easily due to gravity, a robot that can work at such environment could help. Compared with existing drug delivery systems (33-35), which are usually designed to work in liquid media (gastric juice and blood), our M-skin millirobot could achieve effective locomotion on different surfaces and in different media. That makes it a useful tool for the task in complex cavities, such as esophagus, stomach, and intestine. Moreover, the controllable disintegration property of the covered M-skin endows existing pills with an ability to release on demand, for instance, only releasing in the infection region rather than scattering randomly in the whole organ.

[0125] To demonstrate the adaptive locomotion and controllable drug releasing ability, a nondeformable ellipsoidal capsule was converted into an M-skin millirobot by coating it with M-spray. The capsule shell was cut into two halves and agglutinated with M-spray to achieve controllable drug release by disintegrating the M-skin. As illustrated in FIG. 6E, the constructed adaptive drug capsule contains three layers in total, i.e., M-skin cover (thickness, ˜100 μm), middle capsule shell (short axis, 8 mm; long axis, 14 mm), and the internal drugs (dyed by red stain Rhodamin 6G for visualization). Under the actuation of magnetic field, the constructed M-skin capsule was able to locomote at different modes including, but not limited to, slipping, flipping, and rolling, which correspond to the environment. For instance, the M-skin capsule could swing with a small amplitude of ˜3 mm to decrease the friction from the ground, reach a motion speed of ˜1 mm/s by adopting the longitudinal slipping motion along the groove of creases in the narrow curved channel (locomotion type i), flip across the staggered creases with a ˜5 times higher speed than slipping in the large crease area (locomotion type ii), and roll with a ˜10 times higher speed than slipping on the relatively open and flat space (locomotion type iii). Even challenged by the slippery surface and viscous resistance of the ropy gastric juice, the locomotion of M-skin capsule was still controllable and efficient (FIG. 6F). After reaching the target lesion, by applying the oscillating magnetic field (10 mT, 1 Hz), the connection between two halves of the capsule became unstable, and the drug (red stain) began to seep through the crevice.

In Vivo Demonstration in Rabbit Stomach Model

[0126] To further verify the feasibility and effectiveness of an M-spray-enabled millirobot for biomedical applications, an in vivo drug delivery test was conducted in the rabbit stomach using the M-skin capsule. As illustrated in FIG. 7A, the targeted region was set at the end of the stomach and close to the intestine. To demonstrate the drug delivery both in vivo (ultrasound imaging) and in vitro (cutting open stomach), microglass beads (500 μm) and biological stain (Indigo carmine, Phygene Scientific, PH9195) were encapsulated into the capsule. During the experiment, 1.0-g beads for control group 1 and 0.05-g biological stain for control group 2 were orally administered, whereas the M-skin capsule contained 1.0-g beads for experiment group 1 and 0.05-g biological stain for experiment group 2. These four rabbit groups underwent 8 hours of fasting treatment before the experiment, and water feeding and anesthesia were kept during the whole experiment process (Materials and Methods).

[0127] Owing to the covering of M-skin, the capsule in the stomach can be detected by radiology imaging [digital subtraction angiography (DSA), CGO-2100, Wandong], the position and orientation of which can then be used as a feedback for the robot actuation by magnetic field. As the time-lapse radiology images (from experiment group 1) in FIG. 7B show, the constructed M-skin capsule tolerated the ropy and the acid environment and achieved controllable locomotion with an “O” trajectory in the stomach. When the M-skin capsule approached the designed targeted region, the M-skin was disintegrated by applying the oscillating magnetic field to controllably release the encapsulated beads and stain. FIG. 7C gives the in vivo comparison results of the microbead release by ultrasound imaging. It indicates that the M-skin capsule can concentrate the beads' release on the targeted region, i.e., the bright region on the stomach wall, whereas the distribution of beads was almost sparse and could be hardly detected in control group 1. To further intuitively demonstrate the targeted diffusion and retention of drug, the beads were replaced by biological stain and repeated the control experiment with the same process. Then, the rabbits were euthanized, and their stomachs were collected to observe the distribution of biological stain after half an hour. As illustrated in FIG. 7D, comparing with the unintended diffusion in control group 2, the active drug delivery of M-skin capsule in experiment group 2 could effectively enhance the retention and the concentration of drug in specific lesions (˜150 mm.sup.2). These results suggest that the constructed M-skin capsule is feasible and effective for in vivo drug delivery.

DISCUSSION

[0128] Constructing a robot that can effectively adapt to different environments and interact with diverse objects is a grand challenge in robotics. Considering that target objects usually vary from each other in size, shape, and structure, it is challenging to develop an end effector or robot to handle all cases. Moreover, for the tasks in limited space, e.g., object transportation, the acceptable size increment superposed to the target is strictly limited, which raises higher demand for the robot design at small scale.

[0129] A simple fabrication process for on-demand milli-robots is therefore provided herein. The present invention leverages the adhesiveness and wetting ability of M-spray to turn a variety of milli-objects into millirobots regardless of the surface condition, e.g., flat or curve and hydrophilic or hydrophobic. Because the M-skin only accounts for a small volume ratio, it is able to preserve the original size, morphology, and structure of covered objects. Because the structure of an inanimate target is fully used for locomotion, the constructed robot demonstrates high working efficacy and loading ability, which can reach up to thousand-fold of its own volume and hundredfold of its own weight. Moreover, our millirobots are also reprogrammable and can demonstrate multimodal locomotion, thus enabling our robots to better adapt to various environments. Note that the M-spray is unharmful to the host owing to its disintegrable properties. The strategy of turning inanimate objects into moveable millirobots on demand can quickly realize the effective object operation, offering potentials for manipulation, transportation, and delivery in unpredictable, limited spaces.

[0130] The foregoing description of the present invention has been provided for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations will be apparent to the practitioner skilled in the art.

[0131] The embodiments were chosen and described in order to best explain the principles of the invention and its practical application, thereby enabling others skilled in the art to understand the invention for various embodiments and with various modifications that are suited to the particular use contemplated.

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