WO2024237907A1

WO2024237907A1 - A medical device for preventing fouling of surfaces of the medical device

Info

Publication number: WO2024237907A1
Application number: PCT/US2023/022152
Authority: WO
Inventors: Robert Lee KRAMM III
Original assignee: Visual Pathways Consulting Inc
Current assignee: Visual Pathways Consulting Inc
Priority date: 2023-05-13
Filing date: 2023-05-13
Publication date: 2024-11-21
Anticipated expiration: 2025-11-13

Abstract

A medical device for preventing fouling of surfaces of the medical device. Further, the medical device may include a substrate and a plurality of nanostructures. Further, the substrate may include a surface. Further, the surface of the substrate forms at least one surface of the medical device. Further, the plurality of nanostructures may be comprised on the surface of the substrate. Further, the plurality of nanostructures allows forming of a layer of nanobubbles on the surface of the substrate by submerging the surface of the substrate in one or more liquids. Further, the plurality of nanostructures entrains nanobubbles between the plurality of nanostructures for the forming of the layer of nanobubbles on the surface of the substrate. Further, the layer of nanobubbles isolates the surface of the substrate from the one or more liquids for preventing the fouling of the surfaces of the medical device.

Description

A MEDICAL DEVICE FOR PREVENTING FOULING OF SURFACES OF THE

MEDICAL DEVICE

FIELD OF THE INVENTION

Generally, the present disclosure relates to the field of medical and laboratory equipment. More specifically, the present disclosure relates to a medical device for preventing fouling of surfaces of the medical device.

BACKGROUND OF THE INVENTION

The growing demand for complex medical devices including implants, surgical equipment, catheters, and other invasive devices, drives the need for innovative and biocompatible, high-performance coatings that can meet the operational, clinical, and engineering requirements for functionalities of these devices.

For some currently available devices, surface coatings are applied to minimize fouling of the device in use. However, it is still challenging to maintain the pristine surface properties for an extended period of time as the device (i.e. implants) in some cases needs to function for decades.

For a flow control device, the presence of surface fouling can increase the hydrostatic resistance, and cause pressure fluctuation. An example of a flow control device is an implant tube which is used to shunt small amounts of fluid within the body. Further, for an implant tube that has lumens with small dimensions (i.e. tens of micrometers), a clean and antifouling surface is even crucial, as the flow may be blocked by deposited biomaterials in the lumens leading to failure of the implant tube.

Further, the function of some medical implants requires maintenance of the original surface properties. For example, optical clarity is important for some implants such that biofouling of the surface would degrade performance over time due to scattering of the light by the adsorbed substances, and possibly necessitate surgical removal. In some existing implant designs, the surface may be coated with heparin to reduce biofouling (e.g. fibrosis). As a result, different surface coating technology is needed for these implants to extend their functional lifetime.

Further, existing medical devices such as glaucoma implants, punctal/lacrimal devices with or without a lumen, intraocular implants with or without a lumen, corneal devices, intraocular pressure sensing devices, contact lenses, retinal prostheses, orbital implants/ ophthalmic conformers, Scleral Buckles/Inlays, drug and gene delivery devices, and so on, performance degrade by fouling of surfaces of these devices. Therefore, an innovative surface coating technology is needed for these devices to extend their functional life because their performance can be degraded by the fouling of the surfaces.

Therefore, there is a need for an improved medical device for preventing fouling of surfaces of the medical device that may overcome one or more of the above-mentioned problems and/or limitations.

SUMMARY OF THE INVENTION

This summary is provided to introduce a selection of concepts in a simplified form, which are further described below in the Detailed Description. This summary is not intended to identify key features or essential features of the claimed subject matter. Nor is this summary intended to be used to limit the claimed subject matter’s scope.

Disclosed herein is a medical device for preventing fouling of surfaces of the medical device, in accordance with some embodiments. Accordingly, the medical device may include a substrate and a plurality of nanostructures. Further, the substrate may include a surface. Further, the surface of the substrate forms at least one surface of the medical device. Further, the plurality of nanostructures may be comprised on the surface of the substrate. Further, the plurality of nanostructures allows forming of a layer of nanobubbles on the surface of the substrate by submerging the surface of the substrate in one or more liquids. Further, the plurality of nanostructures entrains nanobubbles between the plurality of nanostructures for the forming of the layer of nanobubbles on the surface of the substrate. Further, the layer of nanobubbles isolates the surface of the substrate from the one or more liquids for preventing the fouling of the surfaces of the medical device. Further disclosed herein is a medical device for preventing fouling of surfaces of the medical device, in accordance with some embodiments. Accordingly, the medical device may include a substrate, a plurality of nanostructures, and a layer of lubricant. Further, the substrate may include a surface. Further, the surface of the substrate forms at least one surface of the medical device. Further, the plurality of nanostructures may be comprised on the surface of the substrate. Further, the layer of lubricant may be infused with the surface of the substrate comprising the plurality of nanostructures. Further, the plurality of nanostructures allows forming of a layer of nanobubbles on the surface of the substrate by submerging the surface of the substrate in one or more liquids. Further, the plurality of nanostructures entrains nanobubbles between the plurality of nanostructures for the forming of the layer of nanobubbles on the surface of the substrate. Further, the layer of nanobubbles isolates the surface of the substrate from the one or more liquids for preventing the fouling of the surfaces of the medical device.

Both the foregoing summary and the following detailed description provide examples and are explanatory only. Accordingly, the foregoing summary and the following detailed description should not be considered to be restrictive. Further, features or variations may be provided in addition to those set forth herein. For example, embodiments may be directed to various feature combinations and sub-combinations described in the detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate various embodiments of the present disclosure. The drawings contain representations of various trademarks and copyrights owned by the Applicants. In addition, the drawings may contain other marks owned by third parties and are being used for illustrative purposes only. All rights to various trademarks and copyrights represented herein, except those belonging to their respective owners, are vested in and the property of the Applicants. The Applicants retain and reserve all rights in their trademarks and copyrights included herein, and grant permission to reproduce the material only in connection with reproduction of the granted patent and for no other purpose. Furthermore, the drawings may contain text or captions that may explain certain embodiments of the present disclosure. This text is included for illustrative, non-limiting, explanatory purposes of certain embodiments detailed in the present disclosure.

FIG. 1 is a cross sectional front perspective view of a medical device 100 for preventing fouling of surfaces of the medical device 100, in accordance with some embodiments.

FIG. 2 is a cross sectional front perspective view of the medical device 100 with the layer of lubricant 202 for preventing fouling of surfaces, in accordance with some embodiments.

FIG. 3 is a cross sectional front perspective view of a lumen 302 of a medical device 300 for preventing fouling of surfaces of the medical device 300, in accordance with some embodiments.

FIG. 4 is a cross sectional front perspective view of a lumen 402 of a medical device 400 for preventing fouling of surfaces of the medical device 400, in accordance with some embodiments.

FIG. 5 is a cross sectional front perspective view of a medical device 500 for preventing fouling of surfaces of the medical device 500, in accordance with some embodiments.

FIG. 6 is a cross sectional front perspective view of the medical device 500 with the layer of lubricant 602 for preventing fouling of surfaces, in accordance with some embodiments.

FIG. 7 is a cross sectional front perspective view of a medical device 700 for preventing fouling of surfaces of the medical device 700, in accordance with some embodiments.

FIG. 8 is a partial view of a medical device 800 for preventing fouling of surfaces of the medical device 800, in accordance with some embodiments. DETAIL DESCRIPTIONS OF THE INVENTION

As a preliminary matter, it will readily be understood by one having ordinary skill in the relevant art that the present disclosure has broad utility and application. As should be understood, any embodiment may incorporate only one or a plurality of the above-disclosed aspects of the disclosure and may further incorporate only one or a plurality of the abovedisclosed features. Furthermore, any embodiment discussed and identified as being “preferred” is considered to be part of a best mode contemplated for carrying out the embodiments of the present disclosure. Other embodiments also may be discussed for additional illustrative purposes in providing a full and enabling disclosure. Moreover, many embodiments, such as adaptations, variations, modifications, and equivalent arrangements, will be implicitly disclosed by the embodiments described herein and fall within the scope of the present disclosure.

Accordingly, while embodiments are described herein in detail in relation to one or more embodiments, it is to be understood that this disclosure is illustrative and exemplary of the present disclosure, and are made merely for the purposes of providing a full and enabling disclosure. The detailed disclosure herein of one or more embodiments is not intended, nor is to be construed, to limit the scope of patent protection afforded in any claim of a patent issuing here from, which scope is to be defined by the claims and the equivalents thereof. It is not intended that the scope of patent protection be defined by reading into any claim limitation found herein and/or issuing here from that does not explicitly appear in the claim itself.

Thus, for example, any sequence(s) and/or temporal order of steps of various processes or methods that are described herein are illustrative and not restrictive. Accordingly, it should be understood that, although steps of various processes or methods may be shown and described as being in a sequence or temporal order, the steps of any such processes or methods are not limited to being carried out in any particular sequence or order, absent an indication otherwise. Indeed, the steps in such processes or methods generally may be carried out in various different sequences and orders while still falling within the scope of the present disclosure. Accordingly, it is intended that the scope of patent protection is to be defined by the issued claim(s) rather than the description set forth herein.

Additionally, it is important to note that each term used herein refers to that which an ordinary artisan would understand such term to mean based on the contextual use of such term herein. To the extent that the meaning of a term used herein — as understood by the ordinary artisan based on the contextual use of such term — differs in any way from any particular dictionary definition of such term, it is intended that the meaning of the term as understood by the ordinary artisan should prevail.

Furthermore, it is important to note that, as used herein, “a” and “an” each generally denotes “at least one,” but does not exclude a plurality unless the contextual use dictates otherwise. When used herein to join a list of items, “or” denotes “at least one of the items,” but does not exclude a plurality of items of the list. Finally, when used herein to join a list of items, “and” denotes “all of the items of the list.”

The following detailed description refers to the accompanying drawings. Wherever possible, the same reference numbers are used in the drawings and the following description to refer to the same or similar elements. While many embodiments of the disclosure may be described, modifications, adaptations, and other implementations are possible. For example, substitutions, additions, or modifications may be made to the elements illustrated in the drawings, and the methods described herein may be modified by substituting, reordering, or adding stages to the disclosed methods. Accordingly, the following detailed description does not limit the disclosure. Instead, the proper scope of the disclosure is defined by the claims found herein and/or issuing here from. The present disclosure contains headers. It should be understood that these headers are used as references and are not to be construed as limiting upon the subjected matter disclosed under the header.

The present disclosure includes many aspects and features. Moreover, while many aspects and features relate to, and are described in the context of a medical device for preventing fouling of surfaces of the medical device, embodiments of the present disclosure are not limited to use only in this context.

Overview: The present disclosure describes a medical device for preventing fouling of surfaces of the medical device. Further, the medical device may include a layer of nanobubbles formed on a surface of a substrate of the medical device. Further, the nanobubbles are very small bubbles that are immobilized on a solid surface with diameters ranging from several nanometers to a few hundred nanometers. Further, the nanobubbles are typically composed of a gas (such as air or nitrogen) surrounded by a liquid medium. Further, the nanobubbles have applications in various non-medical fields such as separation technology, water treatment, and self-cleaning and antifouling surfaces. When used in flow conditions, the nanobubbles on the surface have been shown to reduce the drag for the flow along the walls and enhance the flow transport due to slippery boundary conditions.

Further, the nanobubbles may be formed on the surface where a solid substrate is submerged in a liquid medium with oversaturated gas in the liquid medium (1,2). Further, the overs aturation of gas may be created by mixing two liquids (3), pressure reduction (4), temperature increase (5), or gas-evolution chemical reactions (6). The physical and chemical properties of the surface of the solid substrate are important to the probability and the size of the nanobubbles. Further, a surface with a high affinity to the gas phase in the surrounding liquid is preferable for the formation of the nanobubbles. Further, the nanostructures on the surface which have atomically sharp edges (7) or nano-grooves (8) are also beneficial for the formation of the nanobubbles. Further, on any surface of a solid substrate, one of the requirements for the formation and stability of the nanobubbles is the gas overs aturation level, although the process of creating gas overs aturation may differ. Further, a process of creating gas oversaturation may include mixing a water-soluble organic solvent (such as short-chained alcohols) with water, nanobubbles form from the overs aturation due to the solubility reduction. For many types of gases, including carbon dioxide, the solubility of the gas in a water-soluble organic solvent is higher than in water. Moreover, the solubility of gas does not decrease with the increase of water concentration linearly. At the rapid mixing of the organic solvent with water, the gas becomes oversaturated in the solution of the organic solvent in water. This oversaturation level is temporary if the solution is in an open system as the gas can diffuse out. Even under these conditions, this temporal overs aturation of the gas is sufficient to lead to the formation of nanobubbles on the surface of the solid substrate with appropriate physical and chemical properties. A process closely relevant to biological systems is nanobubble formation as the salinity of water changes. In this process, dissolved air is oversaturated as fresh water is mixed with a salt solution. Further, the nanobubbles may be formed in water from temperature fluctuation (9). The reason is that the solubility of air decreases non-monotonically with the increase in temperature. Less oxygen and nitrogen can be dissolved in warmer water. As cool water in equilibrium with air is heated quickly, the dissolved air can reach oversaturation in water, which leads to the formation of nanobubbles on the surface of the walls inside a container. Bubble formation under pressure release is a daily phenomenon when a can of carbonated drink is open. These bubbles have already grown large enough to be visible. If such pressure reduction takes place in a controlled way, nanobubbles may form on the surfaces.

Further, the nanobubbles may be pre-formed on the surface of hard materials that are hydrophobic, or inside soft hydrogel materials with nanocarriers or local hydrophobic domains that can nucleate and stabilize nanobubbles. Oxygen gas molecules diffused from ambient air when the eyes are open can help maintain the liquid medium rich in gas and maintain the long-term stability of nanobubbles. Further, the nanobubbles formed on the surface of the substrate may isolate the substrate from the surrounding medium (liquid medium), and hence reduce the attachment of macromolecules, particles, cells, bacteria, or other objects in the liquid environment to the surface of the solid substrate. Examples of a non-lumened device type where optical clarity is important are corneal inlays, contact lenses, and intraocular devices, which range from simple artificial lenses to telescopic designs that can aid the blind eyes. The biomaterials suitable for ocular devices (such as the medical device) are required to have certain mechanical properties, biocompatibility, and surface properties. Many polymers including polymethyl methacrylate, poly(hydroxy ethyl methacrylate), and silicone have been used for the ocular devices (10). The surface of these polymers can be modified with nanostructures to facilitate the formation and stability of surface nanobubbles. Further, the nanobubbles formed on the hemodialysis membranes (such as the medical device) may remain on the hemodialysis membrane to help eliminate the fouling from the adsorption of biomolecules. The dissolved gas in the bloodstream can help to stabilize the nanobubbles.

Further, the nanobubbles on the surface have an important impact on interfacial phenomena. The long-range attractive interactions between two hydrophobic surfaces immersed in water lead to the adsorption of proteins and other biomacromolecules on the surface (11). And the nanobubbles on the surface reduce the drag along the walls and reduce the pressure drop in the flow transportation (12). The condition is known as a slippery boundary condition. The drag reduction is particularly significant in microfluidics where the resistance from the wall effect is non-negligible. In addition, the nanobubbles present on the surface isolate the substrate from the surrounding medium and hence reduce the attachment of macromolecules, particles, cells, bacteria, or other objects in the liquid environment to the solid surface.

Further, the fluid transport in small medical devices is essential for the medical device’s performance. Small implant lumens of the medical device provide the channels to allow the fluids (such as aqueous humor) to flow through different parts of the body for delivery of oxygen, and nutrients and maintaining a stable pressure. The inlet and outlet can be <100 micrometers in the inner diameter. The surface of the implant lumen needs to be kept clean and free of clogging for the stable transport of fluids through the lumen. For example, in the management of glaucoma, the fluid circulating in the small lumens must maintain a certain pressure for the eye function. The lifetime of the medical device can be as long as three to four decades.

Further, an environment within the body is suitable to host nanobubble layers. For example, the aqueous humor within the eye is a clear fluid consisting of water, electrolytes, and proteins, resembling blood plasma in composition (13). There are rich dissolved gases in aqueous humor. For example, the content of carbon dioxide in the aqueous humor ranges from about 40 to 60 mm Hg. The temperature in the aqueous humor is relatively low (around 33.7 degrees C). Carbon dioxide and oxygen are continuously exchanged between the aqueous humor and the atmosphere by diffusion through the tear film (14). The partial pressure of dissolved oxygen depends on the internal circulation and the atmosphere outside.

The materials creating the implant lumen of the medical device for current designs may be polymers (e.g. silicone, polypropylene) or metals (e.g. titanium). The surface topography of the lumen material influences the cell adhesion and fouling properties of the devices.

Further, the formation of the nanobubble does not alter the intrinsic surface chemistry of the medical device, as the surface change induced by nanobubbles can be reversible through the formation and disappearance of nanobubbles. Based on the properties of the layer of nanobubbles, it can be formulated for short-term or for long-term persistence.

Further, the nanobubble-modified surface (for example, a lumen’s inner surface of the medical device) of the medical device may be self-cleaning, and antifouling for stable fluid transport.

Further, the composition of the bodily fluid may help stabilize the nanobubble coating (such as the layer of nanobubbles). The gas-liquid interfacial tension is lower in body fluids than in water. The composition of the bodily fluid such as electrodes, pH level, and proteins in the aqueous humor may reduce the interfacial tension, thereby increasing nanobubble stability. For example, the aqueous humor within the eye is rich in gaseous content, such as carbon dioxide and oxygen, both of which are supplied internally and externally. For a lumen of the medical device external to the eye, the temperature of the lumen is notably lower than body temperature, allowing for even greater gas solubility. As the circulating fluid enters the lumen, the gas solubility increases as the aqueous fluid temperature decreases. The energy barrier for the heterogeneous nucleation is reduced by the geometrical structures on the surface thereby helping to stabilize the nanobubble coating within the body.

Further, the nanostructures comprised on the surface of the medical device may be tailored to facilitate the enrichment of a thin interfacial layer of gas, allowing nanobubbles to form through heterogeneous nucleation processes. The energy barrier for nanobubble formation is reduced by the properties of the surface. A second mechanism for nanobubble formation is gas entrainment. For example, the viscous hydrophobic lubricant layer may trap dissolved gas from the aqueous fluid. Such a gas-lubricant composite interface is reported to enhance the drag reduction significantly.

Further, polydimethylsiloxane (PDMS), fluorinated polymers, and some biomolecules (polysaccharides, peptides, or proteins) have excellent stability against biofouling. These and other materials may be grafted to or be intrinsic to the medical device’s material (implant or other) and used as a long-term coating layer in the environment inside the body. The coating layer may help enrich gas at the solid-liquid interface, due to the weak affinity to water. The surface energy of the coating layer is usually low, and the contact angle of water in the air on a smooth surface with the same coating is higher than 90 degrees. The nanoscale interfacial layer with nanobubbles enhances the flow transport, reduces the drag reduction, and prevents fouling.

Further, a thin, oily lubricant layer may be used to infuse the nanostructured surface. The thickness of the layer may be on a molecular level or a few nanometers. The top of an entirely infused surface is homogeneous and smooth as the lubricant fills and covers the physical structures and chemical features on the surfaces. Such surfaces may exhibit the properties to reduce the drag reduction of the fluid. However, at some locations on the surface, the lubricant may be partially depleted with time. The nanobubbles may nucleate and form on the substrate. As the liquid of the lubricant layer is viscous, nanobubbles may be trapped at the solid-lubricant composite surface. The gas-enriched surface can reduce the resistance of the flow and have antifouling properties. Further, the layer of lubricant on the surface entrains nanobubbles and enhances the slippery conditions. Further, the lubricant binds to the medical device’s surface via strong covalent bonds to make it stable over time. Further, gas enriches the lubricant layer, helping reduce the drag of the flow, lubricate the fluid, and keep the device surface clean.

Further, the nanostructures on the surface of the substrate may be pre-treated with functional chemical groups to bind the lubricant layer strongly. The binding between the lubricant layer and the surface may be a noncovalent interaction or a strong covalent bond. The covalently-attached lubricant layer does not change the topography of the surface but provides the lubrication effect. Further, the nanostructures on the substrate include fabricated and intrinsic structures of the substrate materials. Further, the nanostructures may include nano-grooves, nano-wrinkles, nano-wells, nano-pins, nano-mushrooms, nano-pores, and crystalline ultra-smooth surfaces with atomically shape edges. Further, the nanostructures are effective for nanobubble formation. Further, the nanostructures may be fabricated on the surface along the fluid direction. The valleys of the nanostructures provide favorable geometry for bubble nucleation and growth. An interfacial nanoscale gas layer fills the valleys and lubricates the fluid transport. The ridges and the corrugation of the nanostructures provide minimal contact area with the biomolecules or cells in the fluid and hence reduce the attachment of foreign materials on the surface. Further, sophisticated nano-architectures of the nanostructures help the formation and stabilization of nanobubbles and keep the surface of the substrate in Cassie-Baxter state. If infused with the lubricant layer, these nanostructures are vertical to the surface, helping affix the lubricant layer to the surface and entrain nanobubbles between the structures. Further, the nanostructures such as the nanopores may be fabricated on the substrate by depositing nanoparticles. The extended, dendrite aggregates of the nanoparticles may entrain gas into the voids to form nanobubbles, or be infused by lubricant first, and then entrain nanobubbles.

Further, the attachment of the biomolecules may be reduced on ultra-smooth surfaces. The atomic steps on the surface facilitate the formation of nanobubbles. Some mineral surfaces after cleavage are ultra- smooth from the crystalline structures. Further, the nanobubbles form easily on these mineral surfaces even if the surface is hydrophilic. The nucleation of nanobubbles is enhanced by the sharp edges between atomically smooth layers. Further, the two-dimensional biocompatible nanomaterials, such as graphene or reduced graphene oxide, and transition metal dichalcogenide monolayers can be used to create smooth surfaces that facilitate nanobubble formation when deposited onto surfaces.

Further, the lubricant layer may be covalently attached to the surface of the solid substrate. The lubricant layer is usually polymer brushes that are slippery, antifouling, and self-healing. The surface appears to be as smooth as a liquid surface, which has a low hysteresis of the contact angle for water or aqueous solutions. Dissolved gas may infuse into this lubricant layer and enhance the slipperiness and antifouling properties of the surface.

Further, the medical device with the nanobubbles may be used for extracorporeal fluid removal and/or infusion where maintenance of the lumen, filter, or membrane is required. For example, the medical device may be used for performing hemodialysis, which is a bloodcleaning approach to treat end-stage kidney disease where a membrane of the medical device is used to remove toxins in the blood of the patients. The membranes are not implanted but are in contact with blood. The fouling of the membrane from the adsorption of blood components may create an inflammation response and serious complications (15) for the patients. The materials of the membranes are usually polymer nanofibers. Polysulfone is extensively used in membranes, due to its mechanical strength, processability, and other advantageous properties (16). The nanofiber membranes are porous, with voids from networks of nanofibers. Such surface properties of the membranes can be beneficial for the formation and stability of nanobubbles. Once formed, surface nanobubbles may remain on the membrane to help eliminate the fouling from the adsorption of biomolecules. The dissolved gas in the bloodstream can help to stabilize the nanobubbles.

Further, the present disclosure describes a medical device that may be implanted or may not be implanted in the body. Further, the medical device may include a substrate having a surface. Furthermore, the medical device may include a nanobubble-infused coating applied to the surface, the coating resulting in less fouling through inhibition of cell attachment as well as other inhibition of non-cellular fouling materials. Moreover, the nanobubbles may protect the surfaces of the medical device from getting foul and causing problems with their function. Further, for the medical device having a lumen, the nanobubbles on the medical device’s surface can enhance fluid transport, block the attachment of biomolecules, and keep the surfaces clean and pristine. Further, for the medical device without a lumen, the nanobubbles on the medical device’s surface can block the attachment of biomolecules and keep the surfaces clean and pristine maintaining their original qualities such as optical clarity. Further, the surfaces of the medical device may have nanostructures with or without being infused with a thin layer of lubricant.

Further, the medical device comprising a surface or film comprising nanobubbles to prevent fouling of the medical device’s surface has utility in a diverse set of applications inside and outside the body. For example, the medical device with the nanobubbles on the surface of the medical device is useful in medical applications for extracorporeal fluid removal and/or infusion where maintenance of the lumen, filter, or membrane is required. Further, the surface comprising the nanobubbles is useful in medical implants and methods of treating a patient in need of an implant, including ophthalmic implants, orthopedic implants, dental implants, cardiovascular implants, neurological implants, neurovascular implants, gastrointestinal implants, and muscular implants. Further, the layer of nanobubbles has applications in ophthalmology where fouling on the surface of the medical device degrades the performance of the medical device. Further, the medical device may include Glaucoma shunts, stents, and other tube designs (with or without the valve, plate, or adjustable pressure control mechanisms), punctal/lacrimal devices with or without a lumen, intraocular lenses or another capsular or scleral-fixated implant, corneal inlays and artificial corneas (Keratoprostheses), intraocular pressure sensors, an ocular medical device providing sustained release drug and gene delivery from the ocular medical device and incorporating a nanobubble layer into which the therapeutic (medicine) is embedded (with or without stimuli- responsive release), contact lenses (refractive or non-refractive), retinal prostheses, orbital implants/ophthalmic conformers, scleral buckles/inlays, etc.

Further, the present disclosure describes a surface or film comprising nanobubbles to prevent fouling of the medical device surface are disclosed. The surface or film comprising nanobubbles is useful in medical implants and methods of treating a patient in need of an implant, including ophthalmic implants, orthopedic implants, dental implants, cardiovascular implants, neurological implants, neurovascular implants, gastrointestinal implants, and muscular implants. The surface or film comprising nanobubbles is also useful in medical applications for extracorporeal fluid removal and/or infusion.

Further, the present disclosure describes a method to maintain the surface properties of medical devices based on self-replenishing surface nanobubbles. When applied to small lumens, the body fluid can move smoothly inside the small dimensions, due to the slippery surfaces of nanobubbles. When applied to other device surfaces without a lumen, the original surface properties such as optical clarity can be maintained by minimizing fouling of the device. If maintained in a suitable aqueous environment during transport and storage, a nanobubble will maintain the properties necessary to function in vivo due to the pinning effect from the device surface.

Further, the present disclosure describes nanobubble surface-coated medical devices and methods of using the nanobubble surface-coated medical devices.

Further, the present disclosure describes a method of creating a layer of nanobubbles on a medical device. Further, the medical device may include a substrate comprising a surface. Further, the surface of the substrate forms at least one surface of the medical device. Further, the medical device may include a plurality of nanostructures comprised on the surface of the substrate. Further, the plurality of nanostructures may be fabricated on the surface of the substrate. Further, the method may include submerging the surface of the substrate in one or more liquids. Further, the one or more liquids may be oversaturated with at least one gas. Further, the submerging of the surface of the substrate in the one or more liquids creates a layer of nanobubbles on the surface. FIG. 1 is a cross sectional front perspective view of a medical device 100 for preventing fouling of surfaces of the medical device 100, in accordance with some embodiments. Accordingly, the medical device 100 may include a substrate 102 and a plurality of nanostructures 106-110. Further, in an embodiment, the medical device 100 may be implantable in a body of a human. Further, in an embodiment, the medical device 100 may not be implantable in the body.

Further, the substrate 102 may include a surface 104. Further, the surface 104 of the substrate 102 forms at least one surface of the medical device 100. Further, in an embodiment, the substrate 102 may be comprised of at least one hydrophobic material. Further, in an embodiment, the substrate 102 may be comprised of at least one hydrophilic material. Further, in an embodiment, the surface 104 of the substrate 102 may form an inner surface of a lumen of the medical device 100. Further, in an embodiment, the surface 104 of the substrate 102 may form an outer surface of the medical device 100.

Further, the plurality of nanostructures 106-110 may be comprised on the surface 104 of the substrate 102. Further, the plurality of nanostructures 106-110 allows forming of a layer of nanobubbles 112-118 on the surface 104 of the substrate 102 by submerging the surface 104 of the substrate 102 in one or more liquids. Further, the one or more liquids may include an aqueous solution. Further, the one or more liquids may include a bodily fluid. Further, the bodily fluid may include blood, plasma, aqueous humor, etc. Further, the plurality of nanostructures 106-110 entrains nanobubbles between the plurality of nanostructures 106-110 for the forming of the layer of nanobubbles 112-118 on the surface 104 of the substrate 102. Further, the layer of nanobubbles 112-118 isolates the surface 104 of the substrate 102 from the one or more liquids for preventing the fouling of the surfaces of the medical device 100. Further, in an embodiment, each of the plurality of nanostructures 106-110 may have a shape corresponding to a geometry. Further, in an embodiment, the plurality of nanostructures 106-110 may be nano-grooves.

Further, in some embodiments, at least one of the plurality of nanostructures 106-110 may be comprised of at least one surface with at least one edge. Further, the at least one surface may be smooth and the at least one edge may be atomically sharp. Further, in some embodiments, the one or more liquids may be oversaturated with at least one gas.

Further, in an embodiment, an overs aturation of the one or more liquids with the at least one gas corresponds to a level of the oversaturation. Further, the forming of the layer of nanobubbles 112-118 on the surface 104 of the substrate 102 corresponds to a threshold of the level of the overs aturation.

In further embodiments, the medical device 100 may include a layer of lubricant 202 infused with the surface 104 of the substrate 102 comprising the plurality of nanostructures 106-110. Further, in an embodiment, the layer of lubricant 202 may be a viscous hydrophobic lubricant.

Further, in an embodiment, the surface 104 of the substrate 102 may be treated with at least one chemical composition for allowing binding the layer of lubricant 202 to the surface 104 of the substrate 102 comprising the plurality of nanostructures 106-110. Further, the at least one chemical composition may be comprised of at least one functional group. Further, the binding of the layer of lubricant 202 allows the infusing of the layer of lubricant 202 with the surface 104 of the substrate 102.

Further, in some embodiments, each of two nanostructures of the plurality of nanostructures 106-110 forms a valley between each of the two nanostructures. Further, each of the two nanostructures may be adjacent on the surface 104 of the substrate 102. Further, the valley facilitates a bubble nucleation process for the forming of the layer of nanobubbles 112-118. Further, the valley may be a crevice between each of the two nanostructures.

Further, in some embodiments, the plurality of nanostructures 106-110 may be comprised of at least one material. Further, the at least one material may be a two- dimensional biocompatible nanomaterial. Further, the two-dimensional biocompatible nanomaterial may include graphene, reduced graphene oxide, transition metal dichalcogenide monolayers, etc.

Further, in an embodiment, the at least one material may be deposited on the surface 104 of the substrate 102 using at least one material depositing process for forming the plurality of nanostructures 106-110 on the surface 104 of the substrate 102. Further, in some embodiments, at least one of the plurality of nanostructures 106-110 may include at least one of nano-grooves, nano- wrinkles, nano-wells, nano-pins, nanomushrooms, and nano-pores.

Further, in some embodiments, one or more nanobubbles of the layer of nanobubbles 112-118 may be fillable with at least one material. Further, the at least one material may include genetic material, drug product, etc. Further, the one or more nanobubbles may release the at least one material in a presence of at least one external stimulus. Further, the at least one external stimulus may include a change in pH level, a change in temperature level, etc., of the one or more liquids. Further, the presence of the at least one external stimulus corresponds to a stimuli-responsive targeting of the layer of nanobubbles 112-118. Further, the layer of nanobubbles 112-118 with the stimuli-responsive targeting, may undergo physicochemical structural changes that result in a release of the at least one material (such as a drug) at a particular time and a particular location when the layer of nanobubbles 112-118 is exposed to the at least one external stimulus, such as temperature changes, pH changes, light, electric/magnetic fields, and ultrasound.

Further, in some embodiments, the layer of nanobubbles 112-118 formed on the surface 104 of the substrate 102 may be stabilized by at least one fluid associated with the medical device 100. Further, the at least one fluid may be bodily fluid.

FIG. 3 is a cross sectional front perspective view of a lumen 302 of a medical device 300 for preventing fouling of surfaces of the medical device 300, in accordance with some embodiments. Further, the lumen 302 may be comprised of a substrate comprising a surface 304. Further, the medical device 300 may include a layer of nanobubbles 306-316 formed on the surface 304. Further, one or more liquids may flow through the lumen 302 along the layer of nanobubbles 306-316 formed on the surface 304. Further, the layer of nanobubbles 306- 316 isolates the surface 304 from the one or more liquids. FIG. 4 is a cross sectional front perspective view of a lumen 402 of a medical device 400 for preventing fouling of surfaces of the medical device 400, in accordance with some embodiments. Further, the lumen 402 may be comprised of a substrate comprising a surface 404. Further, the medical device 400 may include a plurality of nanostructures 406-408 comprised on the surface 404. Further, the plurality of nanostructures 406-408 allows forming of a layer of nanobubbles 410-412 on the surface 404. Further, the layer of nanobubbles 410-412 may prevent at least one object from attaching to the surface 404. Further, the at least one object may include macromolecules, particles, cells, bacteria, etc.

FIG. 5 is a cross sectional front perspective view of a medical device 500 for preventing fouling of surfaces of the medical device 500, in accordance with some embodiments. Accordingly, the medical device 500 may include a substrate 502 and a plurality of nanostructures 506-512. Further, the plurality of nanostructures 506-512 may be nano-wrinkles. Further, the plurality of nanostructures 506-512 may allow forming of a layer of nanobubbles 514-518 on a surface 504 of the substrate 502.

Further, in some embodiments, the medical device 500 may include a layer of lubricant infused 602 with the surface 504.

FIG. 7 is a cross sectional front perspective view of a medical device 700 for preventing fouling of surfaces of the medical device 700, in accordance with some embodiments. Accordingly, the medical device 700 may include a substrate 702 and a plurality of nanostructures 706-708. Further, the plurality of nanostructures 706-708 may be nano-pores. Further, the plurality of nanostructures 706-708 may allow forming of a layer of nanobubbles 710-712 on the surface 704. Further, the medical device 700 may include a layer of lubricant 714 infused with the surface 704.

FIG. 8 is a partial view of a medical device 800 for preventing fouling of surfaces of the medical device 800, in accordance with some embodiments. Accordingly, the medical device 800 may include a substrate 802, a plurality of nanostructures 806-810, and a layer of lubricant 820.

Further, the substrate 802 may include a surface 804. Further, the surface 804 of the substrate 802 forms at least one surface of the medical device 800.

Further, the plurality of nanostructures 806-810 may be comprised on the surface 804 of the substrate 802.

Further, the layer of lubricant 820 may be infused with the surface 804 of the substrate 802 comprising the plurality of nanostructures 806-810. Further, the plurality of nanostructures 806-810 allows forming of a layer of nanobubbles 812-818 on the surface 804 of the substrate 802 by submerging the surface 804 of the substrate 802 in one or more liquids. Further, the plurality of nanostructures 806-810 entrains nanobubbles between the plurality of nanostructures 806-810 for the forming of the layer of nanobubbles 812-818 on the surface 804 of the substrate 802. Further, the layer of nanobubbles 812-818 isolates the surface 804 of the substrate 802 from the one or more liquids for preventing the fouling of the surfaces of the medical device 800.

Further, in some embodiments, at least one of the plurality of nanostructures 806-810 may be comprised of at least one surface with at least one edge. Further, the at least one surface may be smooth and the at least one edge may be atomically sharp.

Further, in some embodiments, the one or more liquids may be oversaturated with at least one gas.

Further, in an embodiment, an overs aturation of the one or more liquids with the at least one gas corresponds to a level of the oversaturation. Further, the forming of the layer of nanobubbles 812-818 on the surface 804 of the substrate 802 corresponds to a threshold of the level of the overs aturation.

Further, in some embodiments, the surface 804 of the substrate 802 may be treated with at least one chemical composition for allowing binding the layer of lubricant 820 to the surface 804 of the substrate 802 comprising the plurality of nanostructures 806-810. Further, the binding of the layer of lubricant 820 allows the infusing of the layer of lubricant 820 with the surface 804 of the substrate 802.

Further, in some embodiments, each of two nanostructures of the plurality of nanostructures 806-810 forms a valley between each of the two nanostructures. Further, each of the two nanostructures may be adjacent on the surface 804 of the substrate 802. Further, the valley facilitates a bubble nucleation process for the forming of the layer of nanobubbles 812-818.

Further, in some embodiments, the plurality of nanostructures 806-810 may be comprised of at least one material. Further, the at least one material may be a two- dimensional biocompatible nanomaterial.

Further, in an embodiment, the at least one material may be deposited on the surface 804 of the substrate 802 using at least one material depositing process for forming the plurality of nanostructures 806-810 on the surface 804 of the substrate 802.

Although the present disclosure has been explained in relation to its preferred embodiment, it is to be understood that many other possible modifications and variations can be made without departing from the spirit and scope of the disclosure.

REFERENCES

[1] Lohse, D.; Zhang, X. Surface nanobubble and surface nanodroplets. Rev. Mod. Phys. 2015, 87, 981-1035.

[2] Lohse, D.; Zhang, X. Pinning and gas overs aturation imply stable single surface nanobubbles. Phys. Rev. E 2015, 91, 031003.

[3] Zhang, X. H.; Khan, A.; Ducker, W. A. A Nanoscale Gas State. Phys. Rev. Lett. 2007, 98, 136101.

[4] Zhang, X.; Chan, D. Y. C.; Wang, D.; Maeda, N. Stability of Interfacial Nanobubbles. Langmuir 2013, 29, 1017-1023.

[5] Xu, C.; Peng, S.; Qiao, G. G.; Gutowski, V.; Lohse, D.; Zhang, X. Nanobubble formation on a warmer substrate. Soft Matter 2014, 10, 7857-7864. [6] Liu, Y.; Edwards, M. A.; German, S. R.; Chen, Q.; White, H. S. The Dynamic Steady State of an Electrochemically Generated Nanobubble. Langmuir 2017, 33, 1845— 1853.

[7] Zhang, X.; Maeda, N. Interfacial Gaseous States on Crystalline Surfaces. The Journal of Physical Chemistry C 2011, 115, 736-743.

[8] Wang, L.; Wang, X.; Wang, L.; Hu, J.; Wang, C. L.; Zhao, B.; Zhang, X.; Tai, R.; He, M.; Chen, L.; Zhang, L. Formation of surface nanobubbles on nanostructured substrates. Nanoscale 2017, 9, 1078-1086.

[9] Petsev, N. D.; Shell, M. S.; Leal, L. G. Dynamic equilibrium explanation for nanobubbles’ unusual temperature and saturation dependence. Phys. Rev. E 2013, 88, 010402.

[10] Uwaezuoke, O.J., Kumar, P., Pillay, V. et al. Fouling in ocular devices: implications for drug delivery, bioactive surface immobilization, and biomaterial design. Drug Deliv. and Transl. Res. 11, 1903-1923 (2021)

[11] Liu, G.; Wu, Z.; Craig, V. S. J. Cleaning of Protein-Coated Surfaces Using Nanobubbles: An Investigation Using a Quartz Crystal Microbalance. The Journal of Physical Chemistry C 2008, 112, 16748-16753.

[12] Vega-Sanchez, C.; Peppou-Chapman, S.; Zhu, L.; Neto, C. Nanobubbles explain the large slip observed on lubricant-infused surfaces. Nature Communications 2022, 13, 351.

[13] Aqueous Humor, https://www.aao.org/eye-health/anatomy/aqueous-humor, Accessed: 2023-01-30.

[14] Leung, B.; Bonanno, J.; Radke, C. Oxygen-deficient metabolism and corneal edema. Progress in Retinal and Eye Research 2011, 30, 471-492.

[15] Heloisa Westphalen, Amira Abdelrasoul, Ahmed Shoker, Protein adsorption phenomena in hemodialysis membranes: Mechanisms, influences of clinical practices, modeling, and challenges, Colloid and Interface Science Communications, Volume 40, 2021

[16] Shafiq Uz Zaman, Sikander Rafiq, Abulhassan Ali, Muhammad Shozab Mehdi, Amber Arshad, Saif-ur Rehman, Nawshad Muhammad, Muhammad Irfan, Muhammad Shahzad Khurram, Muhammad Khaliq U. Zaman, Abdulkader S. Hanbazazah, Hooi Ren Lim, Pau Loke Show, Recent advancement challenges with synthesis of biocompatible hemodialysis membranes, Chemosphere, Volume 307, Part 2, 2022, 135626

Claims

CLAIMS What is claimed is:

1. A medical device for preventing fouling of surfaces of the medical device, the medical device comprising: a substrate comprising a surface, wherein the surface of the substrate forms at least one surface of the medical device; and a plurality of nanostructures comprised on the surface of the substrate, wherein the plurality of nanostructures allows forming of a layer of nanobubbles on the surface of the substrate by submerging the surface of the substrate in one or more liquids, wherein the plurality of nanostructures entrains nanobubbles between the plurality of nanostructures for the forming of the layer of nanobubbles on the surface of the substrate, wherein the layer of nanobubbles isolates the surface of the substrate from the one or more liquids for preventing the fouling of the surfaces of the medical device.

2. The medical device of claim 1, wherein at least one of the plurality of nanostructures is comprised of at least one surface with at least one edge, wherein the at least one surface is smooth and the at least one edge is atomically sharp.

3. The medical device of claim 1, wherein the one or more liquids is oversaturated with at least one gas.

4. The medical device of claim 3, wherein an oversaturation of the one or more liquids with the at least one gas corresponds to a level of the oversaturation, wherein the forming of the layer of nanobubbles on the surface of the substrate corresponds to a threshold of the level of the oversaturation.

5. The medical device of claim 1 further comprising a layer of lubricant infused with the surface of the substrate comprising the plurality of nanostructures.

6. The medical device of claim 5, wherein the surface of the substrate is treated with at least one chemical composition for allowing binding the layer of lubricant to the surface of the substrate comprising the plurality of nanostructures, wherein the binding of the layer of lubricant allows the infusing of the layer of lubricant with the surface of the substrate.

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7. The medical device of claim 1, wherein each of two nanostructures of the plurality of nanostructures forms a valley between each of the two nanostructures, wherein each of the two nanostructures is adjacent on the surface of the substrate, wherein the valley facilitates a bubble nucleation process for the forming of the layer of nanobubbles.

8. The medical device of claim 1, wherein the plurality of nanostructures are comprised of at least one material, wherein the at least one material is a two-dimensional biocompatible nanomaterial.

9. The medical device of claim 8, wherein the at least one material is deposited on the surface of the substrate using at least one material depositing process for forming the plurality of nanostructures on the surface of the substrate.

10. The medical device of claim 1, wherein at least one of the plurality of nanostructures comprises at least one of nano-grooves, nano-wrinkles, nano-wells, nano-pins, nanomushrooms, and nano-pores.

11. The medical device of claim 1, wherein one or more nanobubbles of the layer of nanobubbles is fillable with at least one material, wherein the one or more nanobubbles releases the at least one material in a presence of at least one external stimulus.

12. The medical device of claim 1, wherein the layer of nanobubbles formed on the surface of the substrate is stabilized by at least one fluid associated with the medical device.

13. A medical device for preventing fouling of surfaces of the medical device, the medical device comprising: a substrate comprising a surface, wherein the surface of the substrate forms at least one surface of the medical device; a plurality of nanostructures comprised on the surface of the substrate; and a layer of lubricant infused with the surface of the substrate comprising the plurality of nanostructures, wherein the plurality of nanostructures allows forming of a layer of nanobubbles on the surface of the substrate by submerging the surface of the substrate in one or more liquids, wherein the plurality of nanostructures entrains nanobubbles between the plurality of nanostructures for the forming of the layer of nanobubbles on the surface of the substrate, wherein the layer of nanobubbles isolates the surface of the substrate from the one or more liquids for preventing the fouling of the surfaces of the medical device.

14. The medical device of claim 13, wherein at least one of the plurality of nanostructures is comprised of at least one surface with at least one edge, wherein the at least one surface is smooth and the at least one edge is atomically sharp.

15. The medical device of claim 13, wherein the one or more liquids is oversaturated with at least one gas.

16. The medical device of claim 15, wherein an overs aturation of the one or more liquids with the at least one gas corresponds to a level of the oversaturation, wherein the forming of the layer of nanobubbles on the surface of the substrate corresponds to a threshold of the level of the oversaturation

17. The medical device of claim 13, wherein the surface of the substrate is treated with at least one chemical composition for allowing binding the layer of lubricant to the surface of the substrate comprising the plurality of nanostructures, wherein the binding of the layer of lubricant allows the infusing of the layer of lubricant with the surface of the substrate.

18. The medical device of claim 13, wherein each of two nanostructures of the plurality of nanostructures forms a valley between each of the two nanostructures, wherein each of the two nanostructures is adjacent on the surface of the substrate, wherein the valley facilitates a bubble nucleation process for the forming of the layer of nanobubbles.

19. The medical device of claim 13, wherein the plurality of nanostructures are comprised of at least one material, wherein the at least one material is a two-dimensional biocompatible nanomaterial.

20. The medical device of claim 19, wherein the at least one material is deposited on the surface of the substrate using at least one material depositing process for forming the plurality of nanostructures on the surface of the substrate.