Methods for preparing omniphobic materials with hierarchical structures and uses thereof

Abstract

The present disclosure relates to methods of making omniphobic materials that are physically and chemically modified at the surface to create hierarchically structured materials with both nanoscale and microscale structures that provide omniphobic properties. Uses of said materials are also disclosed herein, including as flexible tubular structures that repel contaminants.

Description

[Technical field]

[0001] The present disclosure relates to the field of materials engineering. In particular, the present disclosure relates to a method for making omniphobic materials having hierarchical structures and their uses. [Background technology]

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority from co-pending U.S. Provisional Patent Application No. 63 / 260,372, filed August 18, 2021, the contents of which are incorporated herein by reference in their entirety.

[0003] Surface fouling caused by the attachment of bacteria, blood, cells and proteins remains a problem in the biomedical space. Fouling can lead to infection and coagulation-induced thrombosis, which can lead to thromboembolic complications and device failure. Within biosensors, non-specific adsorption of biological entities present in complex fluids such as whole blood and plasma increases background noise, thereby reducing detection sensitivity. On a larger scale, the presence of pathogens on surfaces within clinical environments often leads to hospital-acquired infections with poor prognosis and high costs of treatment.

[0004] Omniphobic lubicant-infused surfaces have been developed through the locking of a lubricant layer onto the surface by intermolecular interactions between the surface and the lubricant. Such surfaces have attracted interest due to their antifouling properties against bacteria and blood in both biomedical devices and biosensing platforms. One well-studied approach involves functionalizing the surface with fluoro-based silanes for the immobilization of biocompatible perfluorocarbon lubricants through interactions between fluorine groups. [1]Although promising, these lubricant layers suffer from poor stability under dynamic fluid flow, such as that found in various biomedical devices, and lose repellency over time. In order to effectively use lubricant-infused surfaces for a wide range of anti-biofouling purposes, it is desirable to increase the retention of the lubricant. To this end, surface texturing has been found to be a means by which lubricant layers can achieve greater stability and retention under flow. [2、3] US Patent No. 9,121,307 B2 describes slippery liquid-infused porous surfaces (SLIPS) that include roughened (e.g., porous) surfaces that can be used to lock lubricating fluids in place. When a microfabricated surface is infused with a lubricant, the structures that make up the surface mediate the diffusion of the lubricant across the surface by capillary wicking. [4] These capillary forces, combined with intermolecular interactions between the treated surface and a compatible lubricant, hold the lubricant layer in place. However, when exposed to more vigorous fluid flow, the shear stress experienced by the surface can act against the capillary forces that help hold the lubricant layer in place, resulting in its degradation. [2] Introducing hierarchy into the microstructure through nanoscale modifications overcomes this obstacle, since the presence of nanoscale entities substantially increases capillary forces.

[0005] To simplify the fabrication of lubricant-infused hierarchical surfaces that are expected to exhibit improved biological repellency and strong lubricant retention, a recent strategy has successfully modified heat-shrinkable polystyrene using scalable chemical treatments to form hierarchical, micro- and nanostructured surfaces. [5]WO 2020 / 243833 A1 describes omniphobic materials that are physically and chemically modified at their surfaces to create hierarchically structured materials with both nanoscale and microscale structures that provide omniphobic properties. A polystyrene substrate was first coated with a stiff layer of nanoparticles and fluorosilane. Subsequent thermal shrinkage resulted in the formation of microscale wrinkles with nanoscale features due to the stiffness difference between the nanoparticle coating and the underlying polymer. [5、6] Although a promising technology, the resulting surfaces lack optical transparency due to their light scattering nanoparticle coating and exhibit limited flexibility due to the inherent stiffness of the polymer substrate after shrinkage. In the case of wearable devices, transparency avoids visual obstruction when the device is worn on the eye, making skin-worn devices less visible. Transparency also allows the incorporation of light-sensing components into such devices, substantially enhancing their functionality. At the same time, the limited flexibility of these surfaces limits their incorporation into applications requiring non-planar form factors, such as tubular medical devices and wearable sensors. Summary of the Invention

[0006] The present disclosure provides a method for fabricating a material having a hierarchical structured surface, comprising: a) obtaining a mold containing microscale wrinkles and nanoscale features; b) depositing an elastomeric polymer onto said mold; c) curing an elastomeric polymer on said mold; d) removing the elastomeric polymer from the mold to expose a hierarchically structured surface; e) activating the elastomeric polymer by oxidation of said surface; f) coating said surface with lubricant tethering molecules to create at least one layer of lubricant tethering molecules; The present invention provides a method comprising:

[0007] The present disclosure provides a method for fabricating a material having a hierarchical structured surface, comprising: a) providing a mold containing microscale wrinkles and nanoscale features; b) depositing an elastomeric polymer onto said mold; c) curing an elastomeric polymer on said mold to provide a cured elastomeric polymer; d) removing the cured elastomeric polymer from the mold to expose a hierarchically structured surface of the cured elastomeric polymer; e) activating said surface of the cured elastomeric polymer by oxidation; f) coating at least a portion of said activated surface with lubricant-tethering molecules to obtain at least one layer of lubricant-tethering molecules on at least a portion of said activated surface of the elastomeric polymer; The present invention provides a method comprising:

[0008] The present disclosure provides a method for fabricating a material having a hierarchical structured surface, comprising: a) depositing a moldable polymer onto a mold containing microscale wrinkles and nanoscale features; b) curing a moldable polymer on the mold to provide a cured polymer; and c) removing the cured polymer from the mold to expose at least a structured surface of the cured polymer; The present invention provides a method comprising:

[0009] In some embodiments, the method further comprises: d) activating at least said surface of the cured polymer by oxidation; e) coating at least a portion of the activated surface with lubricant anchoring molecules to obtain at least one layer of lubricant anchoring molecules on at least a portion of the activated surface of the cured polymer; Further includes:

[0010] The present disclosure provides a method for fabricating a material having a hierarchical structured surface, comprising: a) depositing a moldable polymer onto a mold containing microscale wrinkles and nanoscale features; b) curing a moldable polymer on said mold to provide a cured polymer; c) removing the cured polymer from the mold to expose at least a structured surface of the cured polymer; d) activating at least said surface of the cured polymer by oxidation; e) coating at least a portion of the activated surface with lubricant anchoring molecules to obtain at least one layer of lubricant anchoring molecules on at least a portion of the activated surface of the cured polymer; The present invention provides a method comprising:

[0011] The present disclosure provides a method for fabricating a material having a hierarchical structured surface, comprising: a) depositing an elastomeric polymer onto a mold containing microscale wrinkles and nanoscale features; b) curing an elastomeric polymer on said mold to provide a cured elastomeric polymer; c) removing the cured elastomeric polymer from the mold to expose a hierarchically structured surface of the cured elastomeric polymer; d) activating said surface of the cured elastomeric polymer by oxidation; e) coating at least a portion of said activated surface with lubricant anchoring molecules to obtain at least one layer of lubricant anchoring molecules on at least a portion of said activated surface of the elastomeric polymer; The present invention provides a method comprising:

[0012] In some embodiments, the method further comprises depositing a lubricity layer over the at least one lubricity anchoring molecule layer after the coating.

[0013] In some embodiments, the method further comprises treating the template with an anti-sticking agent prior to deposition.

[0014] In some embodiments, the moldable polymer is a pre-cured elastomeric polymer or a thermoplastic polymer. Thus, in some embodiments, the cured polymer is a cured elastomeric polymer or a cured thermoplastic polymer.

[0015] In some embodiments, the method further comprises, after deposition, subjecting the mold with the deposited moldable polymer to a vacuum.

[0016] In some embodiments, activating at least the surface of the cured polymer comprises a plasma treatment.

[0017] In some embodiments, coating a surface with lubricant tethering molecules comprises chemical vapor deposition of the lubricant tethering molecules onto said surface.

[0018] In some embodiments, the elastomeric polymer comprises a silicone elastomer.

[0019] In some embodiments, the elastomeric polymer is polydimethylsiloxane (PDMS).

[0020] In some embodiments, the lubricant tethering molecule comprises a fluorosilane, a fluorocarbon, a fluoropolymer, an organosilane, a polysiloxane, or a mixture thereof.

[0021] In some embodiments, the lubricant tethering molecule layer is a fluorosilane layer or monolayer and is formed using one or more compounds of formula I: [ka] (Wherein, X is a single bond or C 1~6alkylene; n is an integer from 0 to 12; R 1 , R 2 and R 3 are each independently a hydrolyzable group.

[0022] In some embodiments, the fluorosilane comprises trichloro(1H,1H,2H,2H-perfluorooctyl)silane (TPFS) or a fluorosilane of similar composition, in some embodiments, the fluorosilane comprises trichloro(1H,1H,2H,2H-perfluorooctyl)silane (TPFS), 1H,1H,2H,2H-perfluorooctyltriethoxysilane (PFOTS), 1H,1H,2H,2H-perfluorodecyltrichlorosilane (PFDTS), or a mixture thereof.

[0023] In some embodiments, the polysiloxane is formed using one or more compounds of formula II: [ka] (In the formula, R 4 , R 5 and R 6 are each independently a hydrolyzable group; R 7 is C 1~30 alkyl, optionally R 7 is C 10~30 Alkyl or C 20~30 (It is alkyl).

[0024] In some embodiments, the template comprises a surface having a hierarchical structure of microscale wrinkles and nanoscale features. In some embodiments, the hierarchical structure of the template is formed using a process that includes heat shrinking. In some embodiments, the template comprises at least one layer of nanoparticles and at least one layer of lubricant tethering molecules. In some embodiments, the template can be prepared using the process described in WO 2020 / 243833 A1.

[0025] It can be appreciated that the components of the lubricant layer should be selected to be compatible with the lubricant anchoring molecule layer. In some embodiments, the lubricant layer comprises a hydrocarbon liquid, a fluorinated organic liquid, or a perfluorinated organic liquid.

[0026] In some embodiments, the lubricating layer comprises perfluoroperhydrophenanthrene (PFPP).

[0027] In some embodiments, the material is flexible.

[0028] In some embodiments, the material is transparent.

[0029] In some embodiments, the material is repellent to liquids containing biospecies.

[0030] In some embodiments, the material is repellent to bacteria and biofilm formation.

[0031] In some embodiments, the material is repellent to biological fluids.

[0032] In some embodiments, the material is repellent to blood.

[0033] In some embodiments, the material attenuates clotting.

[0034] In some embodiments, the material is not heat shrinkable, hi some embodiments, the cured polymer is not heat shrinkable.

[0035] The present disclosure also provides materials comprising surfaces having hierarchical structures prepared using the methods disclosed herein.

[0036] The present disclosure also provides devices or articles comprising the materials disclosed herein.

[0037] In some embodiments, the material is on a surface of a device or article, hi some embodiments, the material is present on more than one surface of a device or article.

[0038] The present disclosure also provides a device for preventing, reducing, or delaying adhesion, adsorption, surface-mediated clotting, or coagulation of biological material in contact with the device, the device comprising a low-adhesion surface having a hierarchical structure, at least one lubricant tethering molecule layer, and a lubricating layer, the biological material being repelled from the surface. The present disclosure also provides a device comprising a low-adhesion surface having a hierarchical structure, the surface comprising an elastomeric polymer, at least one lubricant tethering molecule layer, and a lubricating layer, the surface comprising a material of the present disclosure, the surface being repelled by biological material. The present disclosure also provides a device of the present disclosure for use in preventing, reducing, or delaying adhesion, adsorption, surface-mediated clotting, or coagulation of biological material in contact with the device.

[0039] The present disclosure also provides a method of preventing, reducing, or delaying adhesion, adsorption, surface-mediated clot formation, or clotting of biological material on a device in contact with the device, comprising providing a device as disclosed herein and contacting the biological material with a low-adhesion surface. The present disclosure also provides a method of preventing, reducing, or delaying adhesion, adsorption, surface-mediated clot formation, or clotting of biological material on a device or article, comprising surface treating the device or article with a material of the present disclosure to obtain a low-adhesion surface on the device or article. In some embodiments, the surface treatment comprises coating the device with a material of the present disclosure. In some embodiments, the surface treatment comprises forming one or more surfaces of the device with a material of the present disclosure.

[0040] Other features and advantages of the present disclosure will become apparent from the following detailed description. However, it should be understood that the detailed description and specific examples, while showing embodiments of the present disclosure, are given by way of example only, and the claims should not be limited by these embodiments, but should be accorded the broadest interpretation consistent with the entire specification.

[0041] Certain embodiments of the present disclosure will now be described in more detail with reference to the accompanying drawings. [Brief description of the drawings]

[0042] [Figure 1] Figure 1 shows an overview of the developed hierarchically structured PDMS surface in an exemplary embodiment of the present disclosure: (a) Schematic of the pattern transfer protocol used to prepare the hierarchically structured PDMS substrate; (b) Scanning electron microscope image of the hierarchically structured PDMS substrate with 1 μm and 100 nm scale bars, respectively; (c) Optical image showing the high degree of (i) transparency and (ii) flexibility of the hierarchically structured substrate; (d) Schematic of post-fabrication surface modification for infusion of lubricant.

[0043] [Diagram 2] FIG. 2 illustrates the structural features effectively transferred by casting (scale bar represents 1 μm) in an exemplary embodiment of the present disclosure, showing a side-by-side comparison of (a) a hierarchically structured polystyrene template and (b) the developed hierarchically structured PDMS surface.

[0044] [Diagram 3] FIG. 3 shows background fluorescence assessed in DAPI (ab), FITC (cd), and TRITC (ef) channels in an exemplary embodiment of the present disclosure: comparative images show wrinkled polystyrene molds (a, c, e) versus hierarchically structured PDMS (b, d, f); scale bars represent 50 μm.

[0045] [Figure 4] FIG. 4 shows the characterization of hierarchically structured PDMS and hierarchically structured TPFS surfaces compared to planar control samples with and without PFPP lubricant-infused in an exemplary embodiment of the present disclosure: (a) contact angles of the four substrate conditions with water and hexadecane (the table below the graph reports the sliding angles of water on the four tested substrates)—no sliding is indicated as a sliding angle >90°; (b) lubricant retention of the four substrate conditions measured gravimetrically (asterisks indicate significance corresponding to *P<0.05, **P<0.01, and ***P<0.001; all reported values ​​are the average of at least three samples, with the associated error bars representing the standard deviation).

[0046] [Diagram 5] FIG. 5 shows results from a colony forming unit assay using MRSA in planar and hierarchically structured TPFS conditions in an exemplary embodiment of the present disclosure - data points are shown on a logarithmic scale and error bars represent standard error from the mean (each measurement consists of at least three data points; **significance indicated by an asterisk corresponding to P<0.01).

[0047] [Figure 6]FIG. 6 illustrates the bacterial adhesion, hemorepellency and antithrombogenic properties testing under static test conditions in an exemplary embodiment of the present disclosure: (a) (i) MRSA and (ii) Pseudomonas aeruginosa (P. (b) colony forming unit assays performed on four classes of surfaces using A. aeruginosa (shown on a logarithmic scale with error bars representing standard error from the mean; each measurement consists of at least three data points); (b) contact angles of human whole blood on planarly and hierarchically structured PDMS; (c) blood stain assays on the six substrate conditions normalized to the planar average value, aligned with representative optical images; (d) thrombin generation values ​​of the six substrate conditions graphed over the duration of the assay - the accompanying table quantitatively summarizes the performance of each condition on the four performance metrics (significance indicated by asterisks corresponding to *P<0.05, **P<0.01 and ***P<0.001; for (b)-(d), all reported values ​​are the average of at least three samples and the accompanying error bars represent standard deviation from the mean).

[0048] [Figure 7] FIG. 7 shows bacterial repellency in a dynamic flow environment of tubing in an exemplary embodiment of the present disclosure: (a) schematic showing the conversion of a flat hierarchically structured substrate to a tubular morphology and subsequent lubricant-infused; (b) fluorescence image of the tubular sample after 48 hours of bacterial flow (scale bar represents 50 μm); (c) relative area of ​​fluorescence normalized to planar PDMS to allow quantification of collected images - area of ​​fluorescence was used instead of number of cells to prevent misidentification of cell clusters; (d) fluorescence, scanning electron microscopy and optical images of the three test conditions (scale bar of scanning electron microscopy image represents 10 μM, scale bar of fluorescence image represents 50 μM); (e) relative fluorescence of whole blood perfused tubing normalized to planar condition (error bars represent standard deviation, asterisks indicate significance corresponding to *P<0.05 and ***P<0.001).

[0049] [Figure 8] FIG. 8 shows results obtained after 24 hours of perfusion of human blood plasma spiked with FITC-fibrinogen in an exemplary embodiment of the present disclosure: (a) planar TPFS-PFPP and (b) hierarchically structured TPFS-PFPP were used for testing (scale bar represents 50 μm); (c) relative fluorescence intensity normalized to the planar TPFS-PFPP condition (error bars represent standard deviation, with asterisks indicating significance corresponding to ***P<0.001). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0050] I. Definition Unless otherwise indicated, it is intended that the definitions and embodiments described in this and other sections are applicable to all embodiments and aspects of the disclosure described herein for which one of ordinary skill in the art would understand that the definitions and embodiments are suitable. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

[0051] In understanding the scope of the present disclosure, the term "comprising" and its variations as used herein are intended to be open-ended terms that specify the presence of the stated features, elements, components, groups, integers, and / or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers, and / or steps. The above also applies to words having similar meanings, such as the terms "including," "having," and their variations. The term "consisting" and its variations as used herein are intended to be closed terms that specify the presence of the stated features, elements, components, groups, integers, and / or steps, but exclude the presence of other unstated features, elements, components, groups, integers, and / or steps. The term "consisting essentially of" as used herein is intended to specify the presence of the stated features, elements, components, groups, integers, and / or steps, as well as those that do not substantially affect the basic and novel characteristic(s) of the features, elements, components, groups, integers, and / or steps.

[0052] As used herein, terms of degree such as "substantially," "about," and "approximately" refer to a reasonable amount of deviation from the modified term so that the end result is not significantly altered. These terms of degree should be interpreted to include a deviation of at least ±5% from the modified term, if the deviation does not negate the meaning of the word that the term modifies. In addition, all ranges given herein include the endpoints of the ranges and any points in the middle of the ranges, whether or not they are explicitly stated.

[0053] As used in this disclosure, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0054] In embodiments that include an "additional" or "second" component, the second component, as used herein, is chemically distinct from the other component or the first component. A "third" component is distinct from the other component, the first component, and the second component, and further listed or "additional" components are similarly distinct.

[0055] As used herein, the term "and / or" means that the listed items may be present or used either individually or in any combination. In effect, the term means that "at least one" or "one or more" of the listed items are used or present.

[0056] The abbreviation "eg" is derived from the Latin exempli gratia and is used herein to indicate a non-limiting example. Thus, the abbreviation "eg" is synonymous with the term "for example." The word "or" is intended to include "and" unless the context clearly dictates otherwise.

[0057] As used herein, the term "creasing" refers to any process for forming wrinkles in a material.

[0058] As used herein, the term "wrinkles" refers to micro- and / or nano-scale folds on the surface of a material.

[0059] As used herein, the term "hierarchical" refers to a material that has both microscale and nanoscale structural features on the surface of the material.

[0060] The term "omniphobic" as used herein with respect to materials refers to materials that exhibit both hydrophobic (low wettability for water and other polar liquids) and oleophobic (low surface tension and low wettability for non-polar liquids) properties. Such omniphobic materials with high contact angles are often recognized as "self-cleaning" materials because contaminants typically bead up and roll off the surface.

[0061] The term "alkyl" as used herein, whether used alone or as part of another group, refers to a straight or branched chain saturated alkyl group, i.e., a saturated carbon chain containing a substituent at one of its termini. The number of possible carbon atoms in a referenced alkyl group is indicated by the numerical prefix "C n1~n2 For example, the term C 1~4 Alkyl means an alkyl group having 1, 2, 3 or 4 carbon atoms.

[0062] As used herein, the term "alkylene," whether used alone or as part of another group, refers to a straight or branched chain saturated alkylene group, i.e., a saturated carbon chain containing substituents at two of its termini. The number of possible carbon atoms in a referenced alkylene group is indicated by the numerical prefix "C n1~n2 For example, the term C 1~6 Alkylene means an alkylene group having 1, 2, 3, 4, 5 or 6 carbon atoms.

[0063] The term "halo" as used herein refers to halogen atoms and includes F, Cl, Br and I.

[0064] As used herein, the term "hydroxyl" refers to the functional group OH.

[0065] The term "suitable" as used herein means that the selection of a particular compound or condition will depend on the particular synthetic operation being performed and the molecule or molecules being transformed, but the selection is well within the skill of one of ordinary skill in the art. All process / method steps described herein are intended to be performed under conditions that allow the reaction to proceed to a sufficient extent to provide the indicated product. One of ordinary skill in the art will understand that all reaction conditions, including, for example, reaction solvent, reaction time, reaction temperature, reaction pressure, reactant ratios, and whether the reaction should be carried out under anhydrous or inert atmosphere, can be varied to optimize the yield of the desired product, and it is within the skill of one of ordinary skill in the art to do so.

[0066] It will be understood that any component, e.g., any particular compound or method step, defined herein as being included may be expressly excluded by a disclaimer or negative limitation, whether implicitly or explicitly defined herein.

[0067] II. Methods and Compositions of the Disclosure

[0068] This disclosure describes a method to create a material that exhibits anti-biofouling properties through a combination of surface hierarchy and maximized lubricant retention. Optionally, the material is flexible and / or transparent. The fabrication process is inexpensive, commercially scalable, and also uses biocompatible reagents that maximize the potential applications of the material in clinical settings. Disclosed herein is a strategy to transfer a wrinkled structure present on a mold, such as a polystyrene mold, with a layered surface onto an elastomeric polymer, such as polydimethylsiloxane (PDMS). PDMS is a transparent, flexible, biocompatible elastomer that exhibits minimal fluorescence. Subsequent fluorosilane treatment and lubricant-infused are introduced to enhance repellency properties. These lubricant-infused, hierarchically structured materials were tested with bacteria and blood to evaluate their inhibition of both biofilm formation and blood staining and clotting, respectively. The materials were then modified into tubular form to evaluate their anti-biofouling properties within clinically relevant flow conditions to ensure their applicability in fluidic systems.

[0069] Accordingly, provided herein is a method for fabricating a material having a hierarchically structured surface, the method comprising the steps of: a) providing a mold containing microscale wrinkles and nanoscale features; b) depositing an elastomeric polymer onto said mold; c) curing an elastomeric polymer on said mold to provide a cured elastomeric polymer; d) removing the cured elastomeric polymer from the mold to expose a hierarchically structured surface of the cured elastomeric polymer; e) activating said surface of the elastomeric polymer by oxidation; f) coating at least a portion of said activated surface with lubricant tethering molecules to obtain at least one layer of lubricant tethering molecules on said activated surface of the elastomeric polymer; A method is provided, comprising:

[0070] Also provided herein is a method for fabricating a material having a hierarchical structured surface, comprising the steps of: a) depositing an elastomeric polymer onto a mold containing microscale wrinkles and nanoscale features; b) curing an elastomeric polymer on said mold to provide a cured elastomeric polymer; c) removing the cured elastomeric polymer from the mold to expose a hierarchically structured surface of the cured elastomeric polymer; d) activating said surface of the elastomeric polymer by oxidation; e) coating at least a portion of said activated surface with lubricant anchoring molecules to obtain at least one layer of lubricant anchoring molecules on said activated surface of the elastomeric polymer; A method is provided, comprising:

[0071] Also provided herein is a method for fabricating a material having a hierarchical structured surface, comprising the steps of: a) depositing a moldable polymer onto a mold containing microscale wrinkles and nanoscale features; b) curing a moldable polymer on said mold to provide a cured polymer; c) removing the cured polymer from the mold to expose at least a structured surface of the cured polymer; d) activating at least said surface of the cured polymer by oxidation; and e) coating at least a portion of the activated surface with lubricant anchoring molecules to obtain at least one layer of lubricant anchoring molecules on the activated surface of the cured polymer; A method is provided, comprising:

[0072] Also provided herein is a method for fabricating a material having a hierarchical structured surface, comprising the steps of: a) obtaining a mold containing microscale wrinkles and nanoscale features; b) depositing an elastomeric polymer onto said mold; c) curing an elastomeric polymer on said mold; d) removing the elastomeric polymer from the mold to expose a hierarchically structured surface; e) activating the elastomeric polymer by oxidation of said surface; f) coating said surface with lubricant tethering molecules to create at least one layer of lubricant tethering molecules; A method is provided, comprising:

[0073] The present disclosure provides a method for fabricating a material having a hierarchical structured surface, comprising: a) depositing a moldable polymer onto a mold containing microscale wrinkles and nanoscale features; b) curing a moldable polymer on the mold to provide a cured polymer; and c) removing the cured polymer from the mold to expose at least a structured surface of the cured polymer; The present invention provides a method comprising:

[0074] In some embodiments, the method further comprises: d) activating at least said surface of the cured polymer by oxidation; e) coating at least a portion of the activated surface with lubricant anchoring molecules to obtain at least one layer of lubricant anchoring molecules on at least a portion of the activated surface of the cured polymer; Further includes:

[0075] In some embodiments, the moldable polymer is an elastomeric polymer, an uncured elastomeric polymer, or a thermoplastic polymer. Thus, in some embodiments, the cured polymer is a cured elastomeric polymer or a cured thermoplastic polymer.

[0076] In some embodiments, the moldable polymer deposited is an elastomeric polymer that uses a curing agent for curing, or an uncured elastomeric polymer. In some embodiments, such elastomeric polymers are known as polymer bases, polymer resins, base resins, or prepolymers. In some embodiments, depositing the uncured elastomeric polymer includes depositing a curing agent with the elastomeric polymer. In some embodiments, depositing the curing agent is performed as a deposition of a mixture including the uncured elastomeric polymer and the curing agent.

[0077] In some embodiments, the method further comprises depositing a lubricity layer over the at least one lubricity anchoring molecule layer after the coating.

[0078] In some embodiments, the method further comprises treating the mold with an anti-sticking agent prior to the depositing. In some embodiments, the anti-sticking agent comprises a fluorosilane, a fluorocarbon, a fluoropolymer, an organosilane, a polysiloxane, or a mixture thereof. In some embodiments, the anti-sticking agent is a lubricating tethering molecule.

[0079] In some embodiments, the method further comprises subjecting the mold with the deposited polymer to a vacuum after said depositing. In some embodiments, a vacuum is used as needed to remove air bubbles from the moldable polymer if they are present. In some embodiments, other methods are used to ensure that the mold is adequately filled with the moldable polymer, such as centrifugation.

[0080] In some embodiments, the elastomeric polymer comprises a silicone elastomer. In some embodiments, the silicone elastomer is cured by platinum catalyzed cure, condensation cure, peroxide cure, or oxime cure systems. In some embodiments, the silicone elastomer is cured by heating. In some embodiments, the silicone elastomer is a commercially available silicone rubber such as EcoFlex™.

[0081] In some embodiments, curing of the elastomeric polymer is carried out according to known procedures for curing elastomeric polymers. In some embodiments, curing is carried out in the presence of a curing agent that is included with the elastomeric polymer when it is deposited onto the mold. In some embodiments, curing is carried out with heating, for example, at a temperature of about 50° C. to about 200° C., about 75° C. to about 175° C., about 100° C. to about 160° C., or about 150° C., for about 1 minute to about 1 hour, about 5 minutes to about 20 minutes, or about 10 minutes.

[0082] In some embodiments, the elastomeric polymer is polydimethylsiloxane (PDMS). In some embodiments, the PDMS is cured by heating, for example, by heating at about 150° C. for about 10 minutes. In some embodiments, the elastomeric polymer comprises a commercially available polysiloxane, such as Sylgard™.

[0083] In such an embodiment, the transfer of the hierarchical structure from the template to the polymer is carried out by a hot embossing process.

[0084] In some embodiments, activating at least the surface of the cured polymer comprises introducing hydroxyl groups into or onto the cured polymer. In some embodiments, activation comprises plasma treatment. In some embodiments, activation comprises oxygen plasma treatment. In some embodiments, plasma treatment is for a time period of about 30 seconds to about 2 minutes, or about 1 minute.

[0085] In some embodiments, activation includes activating more than the surface of the cured polymer, and optionally includes activating the entirety of the cured polymer.

[0086] In some embodiments, coating at least a portion of the activated surface with lubricant tethering molecules comprises chemical vapor deposition (CVD). In some embodiments, CVD is followed by a heat treatment, such as heating at about 50° C. to about 150° C. for about 30 minutes to about 36 hours, or at about 60° C. overnight to about 120° C. for about 1 hour. In some embodiments, the coating is a full coating of the activated surface.

[0087] In some embodiments, the lubricant tethering molecule comprises a fluorosilane, a fluorocarbon, a fluoropolymer, an organosilane, a polysiloxane, or a mixture thereof.

[0088] In some embodiments, the lubricant tethering molecule layer is a fluorosilane layer and is formed using one or more compounds of formula I: [ka] (Wherein, X is a single bond or C 1~6 alkylene; n is an integer from 0 to 12; R 1 , R 2 and R 3 are each independently a hydrolyzable group.

[0089] In some embodiments, the polysiloxane is formed using one or more compounds of formula II: [ka] (In the formula, R 4 , R 5 and R 6 are each independently a hydrolyzable group; R7 is C 1~30 alkyl, optionally R 7 is C 10~30 Alkyl or C 20~30 (It is alkyl).

[0090] A layer may be understood to include single and multiple layers.

[0091] Hydrolyzable group R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently any suitable hydrolyzable group, the selection of which can be made by one of skill in the art. In some embodiments, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently halo or OC 1~4 In some embodiments, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently halo. In some embodiments, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are all independently -OC 1~4 In some embodiments, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are all OEt. In some embodiments, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are all Cl. In some embodiments, X is C 1~6In some embodiments, X is C 1~4 In some embodiments, X is -CH2CH2-. In some embodiments, n is an integer from 3 to 12. In some embodiments, n is an integer from 3 to 8. In some embodiments, n is an integer from 4 to 6. In some embodiments, n is 5. In some embodiments, R 1 , R 2 and R 3 are all Cl, X is -CHCH-, and n is 5. In some embodiments, R 1 , R 2 and R 3 are all OEt, X is -CH2CH2-, and n is 5.

[0092] In some embodiments, R 4 , R 5 and R 6 are all Cl. In some embodiments, R 4 , R 5 and R 6 are all OEt.

[0093] In some embodiments, the fluorosilane layer or monolayer is formed using any fluorocarbon-containing silane, such as, but not limited to, trichloro(1H,1H,2H,2H-perfluorooctyl)silane, 1H,1H,2H,2H-perfluorooctyltriethoxysilane, 1H,1H,2H,2H-perfluorodecyltriethoxysilane, 1H,1H,2H,2H-perfluorododecyltrichlorosilane, 1H,1H,2H,2H-perfluorodecyltrimethoxysilane, trimethoxy(3,3,3 trifluoropropyl)silane, (pentafluorophenyl)triethoxysilane, (3-glycidyloxypropyl)trimethoxysilane, and heptadecafluoro-1,1,2,2-tetrahydrodecyltrichlorosilane, and mixtures thereof.

[0094] In some embodiments, the fluorosilane comprises trichloro(1H,1H,2H,2H-perfluorooctyl)silane (TPFS) and / or fluorosilanes of similar composition. In some embodiments, the fluorosilanes are commercially available.

[0095] In some embodiments, the mold comprises a surface having a hierarchical structure of microscale wrinkles and nanoscale features. In some embodiments, the hierarchical structure of the mold is formed using a process that includes heat shrinking. In some embodiments, the mold comprises at least one nanoparticle layer and at least one lubricant tethering molecular layer. In some embodiments, the mold is prepared using a process described in WO 2020 / 243833 A1. In some embodiments, the omniphobic molecular layer reduces the surface energy of the material and improves omniphobic properties. In some embodiments, the omniphobic molecular layer comprises a fluorosilane.

[0096] It can be appreciated that the components of the lubricating layer should be selected to be compatible with the lubricant anchoring molecule layer. In some embodiments, the lubricating layer comprises a hydrocarbon liquid, a fluorinated organic liquid, or a perfluorinated organic liquid. In some embodiments, the lubricating layer comprises perfluorodecalin, silicone oil, poly(3.3.3-trifluoropropulmethylsiloxane), or a mixture thereof.

[0097] In some embodiments, the lubricating layer comprises perfluoroperhydrophenanthrene (PFPP).

[0098] Also provided herein are materials comprising surfaces having hierarchical structures prepared using the methods described herein. In some embodiments, the materials exhibit both hydrophobic and oleophobic properties. In some embodiments, the materials exhibit omniphobic properties. In some embodiments, the materials exhibit a water contact angle of greater than 160°, a hexadecane contact angle of greater than 100°, and a water sliding angle of less than 5°.

[0099] In some embodiments, the material is flexible. In some embodiments, the moldable polymer, such as an elastomeric or thermoplastic polymer, retains its inherent flexibility after completion of the methods described herein. In some embodiments, the material is a flat flexible film. In some embodiments, the material has a thickness of about 0.3 mm to about 0.8 mm, or about 0.5 mm. It will be appreciated that because the material can be flexible, the material can be bent, folded, or rolled to form different shapes. In some embodiments, the material is shaped into a tube.

[0100] In some embodiments, the material is transparent, hi some embodiments, the moldable polymer, such as an elastomeric polymer or a thermoplastic polymer, retains transparency after completion of the methods described herein.

[0101] In some embodiments, the material exhibits biofouling resistance, hi some embodiments, the material exhibits biofouling resistance in both static conditions and in dynamic environments (i.e., flowing fluid conditions).

[0102] In some embodiments, the material is repellent to liquids containing biological matter. In some embodiments, biological matter includes microorganisms such as bacteria, fungi, viruses, or diseased cells, parasitic cells, cancer cells, foreign cells, stem cells, and infected cells. In some embodiments, biological matter also includes biological matter components such as cell organelles, cell fragments, proteins, nucleic acid vesicles, nanoparticles, biofilms, and biofilm components.

[0103] In some embodiments, the material is repellent to bacteria and biofilm formation. In some embodiments, the surface is repellent to bacteria and biofilm formation. In some embodiments, the bacteria is selected from one or more of gram-negative bacteria or gram-positive bacteria. In some embodiments, the bacteria is selected from one or more of Escherichia coli, Streptococcus species, Helicobacter pylori, Clostridium species, and meningococcus. In some embodiments, the bacteria is selected from the group consisting of Escherichia coli, Salmonella typhimurium, Helicobacter pylori, Pseudomonas aerugenosa, Neisseria meningitidis, Klebsiella aerogenes, Shigella sonnei, Brevundimonas diminuta, Hafnia alvei, Yersinia ruckeri, Actinobacillus actinomycetemcomitans, Achromobacter xylosoxidans, Moraxella osloensis, and the like. The gram-negative bacteria is selected from one or more of Acinetobacter osloensis, Acinetobacter lwoffii, and Serratia fonticola.In some embodiments, the bacteria is a gram-positive bacterium selected from one or more of Listeria monocytogenes, Bacillus subtilis, Clostridium difficile, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, Mycoplasma capricolum, Streptomyces violaceoruber, Corynebacterium diphtheria, and Nocardia farcinica. In some embodiments, the bacteria is Pseudomonas aeruginosa or Staphylococcus aureus. In some embodiments, bacterial adhesion is reduced by about 96%. For example, the reduction in bacterial adhesion can be measured using a bacterial fluorescence assay or an assay that measures bacterial colony forming units.

[0104] In some embodiments, the material is water repellent. In some embodiments, the material is repellent to biological fluids. In some embodiments, the biological fluids are selected from the group consisting of whole blood, plasma, serum, sweat, feces, urine, saliva, tears, vaginal fluid, prostatic fluid, gingival fluid, amniotic fluid, intraocular fluid, cerebrospinal fluid, semen, sputum, peritoneal fluid, pus, nasopharyngeal fluid, wound exudate, aqueous humor, vitreous fluid, bile, cerumen, endolymph, perilymph, gastric juice, mucus, peritoneal fluid, pleural fluid, sebum, vomit, and combinations thereof.

[0105] In some embodiments, the material attenuates clotting, in some embodiments, blood adhesion is reduced by about 95%, in some embodiments, the material exhibits antithrombogenic properties.

[0106] In some embodiments, blood adhesion is determined by incubating the material in blood for about 20 minutes, then placing the material in deionized water and shaking the material in the water for about 30 minutes to allow the blood adhered to the surface to mix into the water, then removing the material from the water and taking an absorbance value of the water to determine the change in the amount of blood (hemoglobin) present on each surface.

[0107] In some embodiments, the material is not heat shrinkable. In some embodiments, the elastomeric polymer is not heat shrinkable. In some embodiments, the cured elastomeric polymer is not heat shrinkable.

[0108] Also provided herein are devices or articles comprising the materials described herein. In some embodiments, the material is on a surface of the device or article, such as coated on the surface. In some embodiments, the material forms a surface of the device or article.

[0109] In some embodiments, the device or article is selected from any healthcare and laboratory device, personal protection equipment, and medical device. In some embodiments, the device or article is selected from a cannula, a connector, a catheter, a catheter, a clamp, a skin hook, a cuff, a retractor, a shunt, a needle, a capillary tube, an endotracheal tube, a ventilator, a ventilator tubing, a drug delivery vehicle, a syringe, a microscope slide, a plate, a film, a laboratory work surface, a well, a well plate, a Petri dish, a tile, a jar, a flask, a beaker, a vial, a test tube, a tubing connector, a column, a container, a cuvette, a bottle, a drum, a vat, a tank, a dental tool, a dental implant, a biosensor, a bioelectrode, an endoscope, a mesh, a wound dressing, a vascular graft, and combinations thereof. In some embodiments, the device is a catheter, such as a urinary catheter or an intravenous catheter.

[0110] In some embodiments, the device is a biosensor, including but not limited to an optical biosensor, hi some embodiments, the optical biosensor includes a fluorescence-based biosensor.

[0111] In some embodiments, the device is a wearable device or article. In some embodiments, the wearable device includes, but is not limited to, a wearable biosensor with a light sensing component. In some embodiments, the wearable device is worn on the eye, e.g., a contact lens-based sensor, or is a skin-worn device, e.g., a wireless health monitoring sensor.

[0112] Also provided herein is a device for preventing, reducing, or delaying adhesion, adsorption, surface-mediated clotting, or coagulation of biological material in contact with the device, comprising a low-adhesion surface with a hierarchical structure, at least one lubricant tethering molecule layer, and a lubricating layer, where the biological material is repelled from the surface. The present disclosure also provides a device comprising a low-adhesion surface with a hierarchical structure, the surface comprising an elastomeric polymer, at least one lubricant tethering molecule layer, and a lubricating layer, the surface comprising a material of the present disclosure, the surface being repelling biological material. The present disclosure also provides a device of the present disclosure for use in preventing, reducing, or delaying adhesion, adsorption, surface-mediated clotting, or coagulation of biological material in contact with the device.

[0113] Also provided herein is a method of preventing, reducing, or delaying adhesion, adsorption, surface-mediated clot formation, or clotting of biological material on a device in contact with the device, comprising providing a device as described herein and contacting the biological material with a low-adhesion surface. The present disclosure also provides a method of preventing, reducing, or delaying adhesion, adsorption, surface-mediated clot formation, or clotting of biological material on a device or article, comprising surface treating the device or article with a material of the present disclosure to obtain a low-adhesion surface on the device or article. In some embodiments, the surface treatment comprises coating the device with a material of the present disclosure. In some embodiments, the surface treatment comprises forming one or more surfaces of the device with a material of the present disclosure. EXAMPLES

[0114] The following non-limiting examples illustrate the present disclosure.

[0115] Example 1. Pattern transfer and characterization of hierarchical structures Materials and Methods

[0116] Reagents. Polydimethylsiloxane (SYLGARD 184) was purchased from Dow Corning (Midland, MI). Trichloro(1H,1H,2H,2H-perfluorooctyl)silane, (3-glycidyloxypropyl)trimethoxysilane, and perfluoroperhydrophenanthrene were both purchased from Millipore Sigma (Oakville, ON).

[0117] Surface fabrication. PDMS was prepared with a weight ratio of base resin:hardener of 10:1. The mixture was stirred for 10 min and placed under vacuum for 20 min to remove air bubbles. The PDMS was then spread over the hierarchically structured polystyrene mold using a spatula to create a coating approximately 0.5 mm thick. To ensure that the PDMS filled the hierarchical structures on the mold, the PDMS-coated mold was placed under vacuum for 25 min. The PDMS layer was then cured upon heating at 150° C. for 10 min. The PDMS layer was carefully separated from the hierarchically structured mold using a spatula. To induce hydroxyl groups on the surface for TPFS attachment, the PDMS substrate was oxygen plasma treated at 25° C. for 1 min. The plasma-treated substrate was placed under a vacuum of −0.08 MPa with 200 μL of TPFS for 3 h, resulting in chemical vapor deposition of silane onto the substrate. An overnight heat treatment at 60° C. ensured the development of a stable self-assembled monolayer of TPFS. PFPP was pipetted onto the substrate immediately prior to its use and excess lubricant was removed by tilting.

[0118] Contact angle and sliding angle measurements. All measurements consisted of at least three data points. A drop shape analyzer (DSA30, Kruss Scientific, Hamburg, Germany) was used for contact angle measurements. Deionized water was dispensed using an automated syringe, while hexadecane and blood were dispensed manually using a pipette. All measurements were taken using a drop volume of 2 μL. Measurements were taken using an automated baseline configuration of the image processing software (Kruss ADVANCE). The sliding angle was measured using a digital angle level (ROK, Exeter, UK) with a drop volume of 5 μL.

[0119] Scanning Electron Microscopy. Due to the micro- and nano-scale features of these surfaces, the use of an electron microscope allowed for a better conceptualization of the topography. Samples were prepared as above and cut to size (approximately 0.5 cm x 0.5 cm). For initial examination, each sample was mounted using carbon tape and nickel paste, then coated with 5 nm of platinum using a sputter coater (Polaron model E1500, Polaron Equipment Ltd., Watford, Hertfordshire). For samples imaged after blood testing, osmium staining was performed before slow dehydration using ethanol. Once immersed in 100% ethanol, these biological samples were dried using a critical point dryer. Mounting and coating were then completed as described above. Samples were imaged from a top-down perspective using a JEOL JSM-7000F.

[0120] Lubricant Retention Test. Samples were cut using a biopsy punch to form 6 mm diameter disks and weighed. 10 μL of PFPP was pipetted onto the surface of each sample and incubated for 2 min. Excess lubricant was removed by tilting the surface and the sample was weighed. The difference in weight before and after lubricant incubation provided a measure of lubricant retention.

[0121] result

[0122] The preparation of hierarchical wrinkled surfaces on heat-shrinkable polymers has been reported previously. [5、6]Briefly, silica nanoparticles were deposited onto ultraviolet ozone (UVO) treated, pre-shrunk polystyrene substrates. (3-aminopropyl)triethoxysilane was used as a crosslinker between the hydroxyl groups on the UVO-treated substrate and the nanoparticles. The nanoparticle-coated substrates were subsequently treated with fluorosilane and heat-shrunk. The resulting substrates served as molds onto which PDMS was cast. These molds were pre-treated with trichloro(1H,1H,2H,2H-perfluorooctyl)silane (TPFS) to ensure that the cast polymer could be easily removed (Figure 1a). A thin layer of PDMS was coated onto these hierarchical molds and subjected to reduced pressure (vacuum) to remove air pockets trapped between the micro / nanofeatures of the mold, thus maximizing the resolution of the transferred pattern. After thermal curing, the solidified PDMS layer was removed from the polystyrene molds to reveal a negative print of the structural features of the mold on the PDMS (Figure 2). Scanning electron microscope (SEM) images confirmed the transfer of both microscale and nanoscale features onto the PDMS substrates (Figure 1b). These substrates also exhibited the desired high degree of transparency and flexibility, as shown in Figure 1c.

[0123] To understand the suitability of these hierarchically structured PDMS substrates for sensing applications, their background fluorescence was evaluated across three fluorescence channels, using a wrinkled polystyrene template for comparison (Figure 3). The PDMS substrates exhibited significantly lower fluorescence across all channels, indicating improved suitability for fluorescence-based sensing platforms compared to their polystyrene counterparts. The hierarchically structured PDMS substrates were then oxygen plasma activated and treated with TPFS to induce the formation of a fluorocarbon self-assembled monolayer (Figure 1d). Such monolayers exhibit high steric effects and low packing density, resulting in improved surface repellency. The repellency of the hierarchically structured and hierarchically structured TPFS surfaces was evaluated by contact angle (CA) and sliding angle (SA) measurements using water (surface tension = 71.99 mN / m) and hexadecane (surface tension = 27.05 mN / m) (Figure 4a). Planar and planar TPFS samples were used as controls. Planar PDMS exhibited hydrophobicity with a CA of 112.8 ± 1.1°, whereas hierarchically structured PDMS demonstrated superhydrophobic behavior with a CA of 153.4 ± 3.6°. Without wishing to be limited by theory, this increase may be attributed to the formation of a Cassie-Baxter wetting state, where contact between water and the surface traps air in the grooves between the microstructures on the surface, inducing an increase in CA. After TPFS treatment, planar PDMS showed slightly improved performance with a CA of 114.9 ± 2.1°, whereas hierarchically structured TPFS surfaces exhibited a CA of 166.7 ± 4.6°. The superhydrophobicity of hierarchically structured and hierarchically structured TPFS surfaces was further supported by the rolling angles of <5° compared to rolling angles of >90° for both planar and planar TPFS. The role of TPFS treatment in improving omniphobicity was highlighted via hexadecane CA, which increased from 28.1 ± 2.1° to 76.3 ± 1.8° for planar PDMS and from 43.5 ± 0.7° to 100.0 ± 6.3° for hierarchically structured PDMS.

[0124] To evaluate how the hierarchical structures interact with lubricants, the difference in lubricant retention between planar (control) and hierarchically structured PDMS substrates, as well as their TPFS-treated counterparts, was investigated (Figure 4b). Samples were weighed before and after a short incubation with perfluoroperhydrophenanthrene (PFPP), a biocompatible lubricant commonly used for clinical applications. Planar TPFS showed an almost two-fold increase in lubricant retention compared to planar PDMS. Without wishing to be limited by theory, this increase may be due to the strong intermolecular interactions between the fluorine groups present on both the PFPP and the treated surfaces. Texturing resulted in a two-fold increase in retention (P<0.05) in the absence of TPFS. This may be due to the larger surface area of ​​the hierarchically structured surfaces where interactions between PFPP and the surface can be formed. Additionally, the grooves between the microscale structures provide pockets that can store larger amounts of lubricant within the pockets. By combining the wrinkling and TPFS treatments, a four-fold increase in lubricant retention was achieved compared to planar PDMS (P<0.001). Considering its combination of strong omniphobicity and efficient lubricant retention, we next investigated whether the hierarchically structured surface with TPFS-PFPP modification exhibited anti-biofouling properties against bacteria and blood.

[0125] Example 2. Bacterial repellency of hierarchically structured PDMS surfaces Materials and Methods

[0126] Reagents. Polydimethylsiloxane (SYLGARD 184) was purchased from Dow Corning (Midland, MI). Trichloro(1H,1H,2H,2H-perfluorooctyl)silane, (3-glycidyloxypropyl)trimethoxysilane, and perfluoroperhydrophenanthrene were both purchased from Millipore Sigma (Oakville, ON). MOPS medium was purchased from TekNova (Hollister, CA, USA). TrypLE Express and FITC dye were purchased from Thermo Fisher Scientific (Burlington, ON, Canada).

[0127] Biofilm culture and experimental set-up. Substrates were cut to size using a 6 mm biopsy punch to ensure consistency of sample surface area. 700 μL of 2% molten agarose (Bioshop, Burlington, Ontario) was added to the wells of a 48-well plate (Corning, USA). Samples were gently inserted into the agarose dispensed into each well. This ensured that the untreated sides and bottom of each substrate were inaccessible during testing. Wells were then allowed to dry overnight to solidify the agarose inlay. Pseudomonas aeruginosa PA01 and Staphylococcus aureus USA300 JE2 (MRSA) were streaked from frozen onto LB agar and grown overnight at 37°C. From this, overnight cultures were diluted 1 / 100 into MOPS minimal medium supplemented with 0.4% glucose and 0.5% casamino acids (TekNova, USA) for P. aeruginosa or tryptic soy broth supplemented with 0.4% glucose and 3% NaCl for MRSA. Each well of the pre-prepared assay plate was filled with 200 μl of the diluted bacterial suspension or control medium without bacterial cells. The assay plate was then incubated at 37° C. without shaking for 72 hours for P. aeruginosa and 24 hours for MRSA to allow biofilms to form on the substrate. After incubation, the agarose inlays containing the substrate were gently removed from each well using sterile forceps and placed in a sterile Petri dish. The substrate was released from each agarose inlay by cutting the surrounding agarose using forceps and then gently submerged three times in sterile water to remove planktonic bacteria. The surfaces were then placed into a clean Petri dish and dried at 37°C for 30 min before being transferred to a new 48-well plate for downstream assays.

[0128] Colony forming unit (CFU) assay. To quantify the colony forming units attached to each surface, 200 μL of recombinant trypsin solution (TrypLE Express, Gibco) was added to each well of a 48-well plate to cover the entire surface. The sample plate was then incubated at 37° C. for 30 min with shaking to disperse the biofilm and attached bacterial cells from the surface. Colony forming units were quantified by plating serial dilutions from each well onto LB agar Petri dishes.

[0129] result

[0130] To understand how surfaces interact with bacteria, bacterial attachment and subsequent biofilm formation was investigated on four classes of PDMS surfaces: planar, planar TPFS-PFPP, hierarchically structured, and hierarchically structured TPFS-PFPP. Planar TPFS and hierarchically structured TPFS were included in some preliminary studies, as well as their non-fluorinated counterparts (Figure 5). Tests were performed using Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa, due to the habitual presence of these pathogens in clinical environments.

[0131] To detect differences in bacterial attachment between the test conditions, samples were subjected to colony forming unit (CFU) assays. After overnight incubation in bacterial culture medium and washing with sterile deionized water, samples were transferred to fresh bacterial growth medium and agitated to release attached bacteria and biofilm. CFU was then determined by serially diluting the bacterial medium and plating on agar plates. The resulting colony formation on the agar plates was used to quantify the number of bacteria released from the surface into the growth medium. Planar, planar TPFS-PFPP and hierarchically structured samples incubated with MRSA produced 8.6 × 10 4 ~3.3×10 5The mean bacterial abundance ranged from 1 × 10 CFU / mL, with non-significant differences among the three conditions (Fig. 6a, i). The planar TPFS-PFPP showed high variability between samples, highlighting the instability of the lubricant layer on its surface. In contrast, the hierarchically structured TPFS-PFPP surface showed low sample-to-sample variability, with 1 × 10 4 The planar, planar TPFS-PFPP and hierarchically structured PDMS showed significantly lower bacterial abundance, approaching CFU / mL - nearly a 1 log reduction compared to the planar condition, corresponding to an 86% reduction in bacterial adhesion (P<0.01). For P. aeruginosa, the planar, planar TPFS-PFPP and hierarchically structured PDMS showed approximately 1 × 10 4 The hierarchically structured TPFS-PFPP showed a similar level of bacterial presence in terms of CFU / mL (Fig. 6a, ii). However, the hierarchically structured TPFS-PFPP showed a nearly 2-log reduction of 1 × 10 2 The results showed a reduction in CFU / mL, corresponding to a 98.5% reduction in bacterial adhesion (P<0.001), and a 99.6% reduction compared to the planar TPFS-PFPP condition (P<0.01). The superior performance against P. aeruginosa compared to MRSA is due to its rod-like structure, which makes capture between the hierarchically structured microscales difficult as a result of steric hindrance; in contrast, the spherical shape of S. aureus allows some degree of capture between the microscale structures on the developed surfaces. These studies indicate that the omniphobic nature of the hierarchically structured TPFS-PFPP surface is reflected in its superior bacterial repellency compared to the other hierarchically structured and planar surfaces tested herein.

[0132] Example 3. Hemophobic and anticoagulant properties of hierarchically structured PDMS surfaces

[0133] Materials and Methods

[0134] Reagents. Polydimethylsiloxane (SYLGARD 184) was purchased from Dow Corning (Midland, MI). Trichloro(1H,1H,2H,2H-perfluorooctyl)silane, (3-glycidyloxypropyl)trimethoxysilane, and perfluoroperhydrophenanthrene were both purchased from Millipore Sigma (Oakville, ON). N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) and calcium chloride were purchased from Bioshop Canada (Burlington, ON). Z-Gly-Gly-Arg-AMC, a thrombin-directed fluorescent substrate, was purchased from Bachem (Bubendorf, Switzerland). Pooled citrated plasma was collected from healthy donors as previously described. [7] Venous blood from healthy volunteers was collected by a qualified phlebotomist in tubes containing sodium citrate. All procedures were approved by the McMaster University Research Ethics Board. Blood samples were collected from consenting subjects into citrated BD collection tubes (Hamilton, Ontario) according to procedures approved by the McMaster Research Ethics Board.

[0135] Blood staining assay. To test for blood staining, samples were immersed in citrated human whole blood for 30 seconds and then transferred to wells filled with 700 μL of deionized water. The well plate (Corning, Canton, NY) containing all the test samples immersed in water was placed on an incubating mini shaker (VWR, Mississauga, ON) for 30 minutes to release any blood attached to the sample. 200 μL from each well containing sample was transferred to a new well plate for optical density measurement using a plate reader (Synergy Neo2, BioTek, Winooski, VT). Blank wells contained 200 μL of deionized water.

[0136] Thrombin generation assay. To examine the antithrombogenic properties of the substrates, a fluorogenic thrombin generation assay was performed. Samples were cut to size using a 6 mm biopsy punch and fixed to the bottom of a black flat-bottom 96-well plate (Evergreen Scientific, Vernon, CA, USA) using Elkem Silbione adhesive (Factor II, Lakeside, AZ). Empty wells were used as controls. 80 μL of citrated plasma was added to each well, followed by 20 μL of 20 mM HEPES buffer (pH 7.4). The plates were then incubated at 37 °C for 10–15 min. A fluorogenic solution was made using a buffer containing the fluorogenic substrate Z-Gly-Gly-Arg-AMC (zGGR) at a final concentration of 20 mM and 25 mM CaCl2 in HEPES. To initiate clotting after incubation, 100 μL of fluorogenic solution was added to each well. The plate was immediately loaded into a SPECTRAmax fluorescent plate reader (Molecular Devices) and substrate hydrolysis was monitored at 1 min intervals for 90 min using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Collected data was analyzed using Technoclone software-Technothrombin TGA protocol (Vienna, Austria). Lag time to thrombin generation (min), peak thrombin concentration (nM), time to peak thrombin concentration (min) and area under the curve or total thrombin generation (Endogenous thrombin potential) (ETP) (nM.min) were calculated and reported using the software.

[0137] result

[0138] As a preliminary assessment of hemorepellency, the CA of human whole blood (surface tension = ∼55 mN / m) was measured for both planar and hierarchically structured surfaces (Figure 6b). Planar PDMS exhibited a CA of 95.8 ± 4.7°, whereas hierarchically structured PDMS exhibited a CA of 143.2 ± 3.1°, thus demonstrating significantly improved repellency (P < 0.0001). Subsequent blood testing evaluated the performance of six conditions: planar, planar TPFS, planar TPFS-PFPP, hierarchically structured, hierarchically structured TPFS, and hierarchically structured TPFS-PFPP. To examine adhesion in an environment that induces greater contact with blood, samples were subjected to a blood stain assay (Figure 6c) in which the substrate was immersed in anticoagulated human whole blood. After submersion in blood, the surface was subsequently added into a well containing water and agitated to release any attached blood. The absorbance of the solution released from the surfaces was measured using spectrophotometry. Hierarchically structured PDMS performed 30% worse than planar PDMS, while planar TPFS and hierarchically structured TPFS performed slightly worse compared to their untreated counterparts, with 10% and 7% increases in absorbance, respectively. Given that surface wrinkling and TPFS treatment both increase hydrophobicity, all three of these increases in blood adhesion could be attributed to hydrophobic interactions between these surfaces and blood proteins. With the introduction of lubricant, planar TPFS-PFPP showed a statistically insignificant improvement in performance compared to planar PDMS. However, hierarchically structured TPFS-PFPP showed a 95% and 96% improvement compared to planar PDMS and untreated hierarchically structured PDMS, respectively (P<0.01, P<0.0001). Based on these observed hemorepellent properties, we further investigated whether the hierarchically structured TPFS-PFPP surface has antifouling properties in environments with increased blood contact duration and induction of clotting.

[0139] To determine whether the observed hemorepellency translated into reduced thrombogenicity, a thrombin generation assay was performed (Figure 6d). Lag time, peak thrombin, time to peak thrombin, and endogenous thrombin potential (ETP) were evaluated, with all four parameters showing similar trends in performance among the conditions tested. Planar TPFS and planar TPFS-PFPP showed slight improvements across all four measurements compared to untreated planar PDMS. Hierarchically structured and hierarchically structured TPFS performed slightly better than their planar counterparts. All of these surfaces still induced significant thrombin generation compared to background conditions. On the other hand, the hierarchically structured TPFS-PFPP surface showed strong antithrombogenicity at or near background levels. This condition was significantly better than all other conditions, as detailed in Table 1. The antithrombogenicity of the hierarchically structured TPFS-PFPP surfaces supports their application within clinical devices, thus proving the need for subsequent studies examining such properties in dynamic environments. Table 1. Summary of P values ​​obtained by analysis of variance comparing the hierarchically structured TPFS-PFPP against all other test conditions in the thrombin generation assay. Significance was established in at least one test parameter for all conditions, with most conditions showing significance across all parameters. NS represents no statistical significance, although an improvement in performance for the hierarchically structured TPFS-PFPP condition was still observed. [Table 1]

[0140] Example 4. Hierarchically structured PDMS repellency under dynamic conditions Materials and Methods

[0141] Reagents. Polydimethylsiloxane (SYLGARD 184) was purchased from Dow Corning (Midland, MI). Trichloro(1H,1H,2H,2H-perfluorooctyl)silane, (3-glycidyloxypropyl)trimethoxysilane, and perfluoroperhydrophenanthrene were both purchased from Millipore Sigma (Oakville, ON). Phosphate buffered saline (pH 7.4) was purchased from Bioshop Canada (Burlington, ON). FITC-conjugated human fibrinogen, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), and calcium chloride were purchased from Bioshop Canada (Burlington, ON). FITC dye was purchased from Thermo Fisher Scientific (Burlington, ON, Canada). Z-Gly-Gly-Arg-AMC, a thrombin-directed fluorescent substrate, was purchased from Bachem (Bubendorf, Switzerland). Pooled citrated plasma was collected from healthy donors as previously described. [7] Venous blood from healthy volunteers was collected by a qualified phlebotomist in tubes containing sodium citrate. All procedures were approved by the McMaster University Research Ethics Board. Blood samples were collected from consenting individuals in citrated BD collection tubes (Hamilton, Ontario) according to procedures approved by the McMaster Research Ethics Board. Escherichia coli K-12 MG1655 transfected with pUA66-GadB harboring green fluorescent protein (GFP) was generously provided by the Brown Laboratory at McMaster University (Hamilton, Ontario).

[0142] Fabrication of tubular test devices. The test surface was rolled onto a 1 mL syringe barrel (BD, Mississauga, Ontario) which provided a structural scaffold. The width of the test surface was equal to the circumference of the barrel, creating a uniform test interface. Attachment to a second syringe barrel using epoxy adhesive (Gorilla Glue, Sharonville, Ohio) resulted in luer locks on each end of the test device. Female barbed luer connectors (Quosina®, Ronkonkoma, NY, 0.89 mm inner diameter) were added to each end to allow attachment to silicone tubing. The resulting device had an inner diameter of 3.78 mm.

[0143] Bacterial flow assay. For E. coli perfusion experiments, green fluorescent protein-expressing pUA66-GadB (10 diluted in PBS) was used. 6 A perfusion medium consisting of 6 mL of E. coli K12MG1655 with 100% CFU / mL was prepared and mixed in the presence of a flame to prevent aerosolization contamination. A four-channel peristaltic pump (Ismatec Reglo, Cole Parmer®, Montreal, QC) was connected to sterile tubing (inner diameter 0.89 mm, Tygon, PA, USA) to form a closed loop of the tubular test device. The loop was rinsed with 70% ethanol and then with PBS at a flow rate of 3 ml / min. Four collection tubes (Corning, Canton, NY) each containing 6 mL of GFP-E. coli were subsequently withdrawn and loaded into the peristaltic pumping reservoir. Pumping was started at a flow rate of 1 mL / min. The bacterial medium was perfused for 48 h. After perfusion, the test surface was gently removed from the system and rinsed with a stationary sterile PBS washing reservoir. After rinsing, the surfaces were imaged using a fluorescence microscope (Eclipse Ti2 series, Nikon®, Melville, NY).

[0144] FITC-fibrinogen preparation. 10 mg of peak 1 fibrinogen was dissolved with FITC dye (Invitrogen, Thermo Fisher Scientific) and the reaction was incubated for 1 h in the dark at room temperature. The reaction product was passed through a PD-10 column packed with Sephadex G-25 beads and 1 mL fractions were collected after incubation. The absorbance was read using a spectrophotometer at 280 nm and 494 nm to determine the protein concentration.

[0145] Blood plasma perfusion assay. Perfusion medium containing equal parts of human platelet poor plasma and HEPES-FITC-fibrinogen solution (final concentration 175ug / mL) was prepared at room temperature and mixed gently by pipetting for 30 seconds. At the same time, a 4-channel peristaltic pump (Ismatec Reglo, Cole Parmer®, Montreal, Quebec) was connected and the sterile tubing was rinsed with HEPES buffer at a high flow rate (3mL / min). Four collection tubes, each containing 6mL of plasma HEPES-FITC-fibrinogen solution, were then drawn off and loaded into the peristaltic pumping reservoir. After connecting the tubular test device, the closed loop was primed with the solution. Pumping was then started at a flow rate of 1mL / min for 24 hours. After perfusion, the test surface was gently removed from the system and rinsed in a static HEPES washing reservoir. After rinsing, images of the surface were acquired using a fluorescent microscope.

[0146] Whole blood perfusion assay. Perfusion medium containing equal parts of citrated human whole blood and HEPES-FITC-fibrinogen solution (final concentration 175ug / ml) was prepared following the same protocol as used for plasma perfusion studies. An 8-channel syringe pump (New Era Pump Systems®, Farmingdale, NY) was connected and sterile tubing was used with HEPES buffer at a flow rate of 3mL / min. Four collection tubes, each containing 5mL of whole blood HEPES-FITC-fibrinogen, were then withdrawn and spiked with 1M calcium chloride solution (12.5mM final concentration) to restore clotting activity. The contents were mixed for 30 seconds and immediately transferred to a 5mL needled syringe (BD, Mississauga, ON), which was loaded into the syringe pump. The tubular test device was then attached and the system was primed with whole blood HEPES-FITC-fibrinogen solution. Pumping was started at a flow rate of 1 mL / min, but the perfusion time was reduced to approximately 25 min - equal to the tubular occlusion point. At this point, the device usually occludes, preventing further perfusion. After perfusion, the surface was removed, rinsed with a HEPES wash reservoir, and imaged using both a fluorescent microscope and a digital color camera.

[0147] result

[0148] Although the hierarchically structured TPFS-PFPP surfaces exhibited excellent anti-biofouling properties in static conditions, the dynamic environments within various biomedical devices and sensing platforms present very different physical and mechanical conditions that need to be considered. Therefore, the developed surfaces were tested under flow to ensure their viability in such applications. The high flexibility of the substrates allowed the modification of the substrates from flat surfaces to tubular devices (Figure 7a). In such conditions, planar substrates, planar TPFS-PFPP substrates and hierarchically structured TPFS-PFPP substrates were tested.

[0149] To test for bacterial repellency, E. coli K12 constitutively expressing green fluorescent protein was incubated for 10 min in phosphate-buffered saline (PBS). 6The lubricant was diluted to a concentration of 1000 CFU / mL and flowed through the tubular device for 48 h. After perfusion, the tubes were dissected, washed, and imaged using a fluorescent microscope (Figure 7b). The planar tubes showed significant bacterial adhesion as indicated by uniform coverage of fluorescent spots across the entire surface. The planar TPFS-PFPP tubes showed a significant improvement over the non-lubricated tubes, while the hierarchically structured TPFS-PFPP surface showed very minimal bacterial adhesion, significantly better than both planar conditions. The extent of bacterial adhesion was quantified based on the area covered with fluorescent bacteria (Figure 7c). Planar TPFS-PFPP showed a 92.5% reduction in bacterial adhesion compared to planar PDMS, while hierarchically structured TPFS-PFPP showed a 96.5% reduction compared to planar PDMS (P<0.0001, P<0.0001). The hierarchically structured TPFS-PFPP showed a 53% reduction compared to the planar TPFS-PFPP ( P < 0.05), indicating the effectiveness of the hierarchical structure on PDMS tubes in preventing bacterial adhesion.

[0150] Blood adhesion and clotting under flow were also investigated. Citrated human blood plasma was tested first to allow for long perfusion times while minimizing the possibility of clotting. FITC-fibrinogen was added to the plasma so that the adhesive fibrin network could be visualized by monitoring fluorescence. The mixture was perfused through the planar and hierarchically structured TPFS-PFPP tubes using pulsatile flow for 24 hours, after which the samples were dissected, briefly washed, and imaged (Figure 8). The planar TPFS-PFPP surface showed an abundant fibrin network heavily coating the surface. In contrast, the hierarchically structured TPFS-PFPP showed minimal fibrin adhesion despite the prolonged perfusion times, as indicated by an 85% reduction in fluorescently labeled fibrin (P<0.001).

[0151] To better replicate clinical conditions, flow studies were then performed using citrated human whole blood spiked with FITC-fibrinogen. Blood was perfused through the planar tube, the planar TPFS-PFPP tube, and the hierarchically structured TPFS-PFPP tube. Calcium chloride was added to the blood immediately prior to perfusion to induce clotting. Flow was continued until the tube was occluded, at which point the sample was imaged optically and fluorescently (Figure 7d). The planar PDMS tube demonstrated extensive blood staining, and a dense fluorescent fibrin network was observed across the entire surface. The planar TPFS-PFPP showed less staining, but a similar abundant fibrin network, mimicking that observed in the plasma study. Again, the hierarchically structured TPFS-PFPP tube showed very minimal blood staining and no fibrin network, as evidenced by a 95.8% reduction in fluorescence compared to either of the planar conditions (Figure 7e, P<0.001, P<0.001). These samples were then imaged by SEM to visualize the blood clots formed on the surface. The planar PDMS surface revealed extensive clotting, with red blood cells and fibrin networks decorating the entire surface (Figure 8d). The planar TPFS-PFPP showed some adhesion of fibrin onto the substrate, but less than that observed on the non-lubricated counterpart. The hierarchically structured TPFS-PFPP substrate showed no signs of clotting or cell attachment, confirming its repellent and antithrombogenic properties under flow. The change in appearance of the hierarchical structures was confirmed to be due to the osmium coating used for SEM sample preparation. Taken together, the effectiveness of the hierarchically structured TPFS-PFPP tube in preventing biofouling under dynamic conditions confirms its ability to address gaps that exist within the biomedical space - particularly within in vivo devices such as intravenous and urinary catheters that currently suffer from extensive biofouling.

[0152] conclusion

[0153] Using the pattern transfer protocol, inexpensive anti-biofouling substrates were developed that address the niches of biomedical spaces through their optical transparency and high degree of flexibility. The combination of hierarchical structuring and lubricant-infusion on these substrates results in significant repellency against biological entities. As demonstrated by the associated control conditions, hierarchical structuring serves two purposes in terms of repellency: liquid repellency through induction of a wetted state and omniphobicity through increased TPFS-mediated lubricant retention.

[0154] Due to its effectiveness in preventing biofouling against bacteria and blood under both static and dynamic conditions, this surface exhibits properties that make it applicable within various biomedical platforms. For example, chip-based and wearable biosensors that suffer from non-specific adhesion of biological entities as well as biomedical devices prone to biofilm formation and thrombosis will benefit from the developed substrate. Considering their tendency to promote both infection and blood-related complications, urinary and intravenous catheters in particular show promising applications of the developed substrate, especially considering its excellent performance under flow, where prolonged perfusion times did not result in performance degradation. Finally, the incorporation of this lubricant-infused hierarchically structured substrate into existing biomedical devices and sensors will help improve performance and resulting clinical outcomes.

[0155] Although the present disclosure has been described with reference to examples, it should be understood that the scope of the claims should not be limited to the embodiments described in the examples, but should be accorded the broadest interpretation consistent with the entire specification.

[0156] All publications, patents, and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference in its entirety. If a term in this disclosure is defined differently in a document incorporated herein by reference, the definition provided herein shall serve as the definition of that term. References (1)Leslie,DC;Waterhouse,A.;Berthet,JB;Valentin,TM;Watters,AL;Jain,A.;Kim,P.;Hatton,BD;Nedder,A.;Donovan,K.;S uper,EH;Howell,C.;Johnson,CP;Vu,TL;Bolgen,DE;Rifai,S.;Hansen,AR;Aizenberg,M.;Super,M.;Aizenberg,J.;Ingber,DEA Bioinspired Omniphobic Surface Coating on Medical Devices Prevents Thrombosis and Biofouling.Nature Biotechnology 2014,32(11),1134-1140.https: / / doi.org / 10.1038 / nbt.3020. (2)Kim,P.;Kreder,MJ;Alvarenga,J.;Aizenberg,J.Hierarchical or Not?Effect of the Length Scale and Hierarchy of the Surface Roughness on Omniphobicity of Lubricant-Infused Substrates.Nano Lett.2013,13(4),1793-1799.https: / / doi.org / 10.1021 / nl4003969. (3)Ware,C.S.;Smith-Palmer,T.;Peppou-Chapman,S.;Scarratt,L.R.J.;Humphries,E.M.;Balzer,D.;Neto,C.Marine Antifouling Behavior of Lubricant-Infused Nanowrinkled Polymeric Surfaces.ACS Appl.Mater.Interfaces 2018,10(4),4173-4182.https: / / doi.org / 10.1021 / acsami.7b14736. (4)Wong,T.-S.;Kang,S.H.;Tang,S.K.Y.;Smythe,E.J.;Hatton,B.D.;Grinthal,A.;Aizenberg,J.Bioinspired Self-Repairing Slippery Surfaces with Pressure-Stable Omniphobicity.Nature 2011,477(7365),443-447.https: / / doi.org / 10.1038 / nature10447. (5)Imani,S.M.;Maclachlan,R.;Rachwalski,K.;Chan,Y.;Lee,B.;McInnes,M.;Grandfield,K.;Brown,E.D.;Didar,T.F.;Soleymani,L.Flexible Hierarchical Wraps Repel Drug-Resistant Gram-Negative and Positive Bacteria.ACS Nano 2020,14(1),454-465.https: / / doi.org / 10.1021 / acsnano.9b06287. (6)Imani,S.M.;Maclachlan,R.;Chan,Y.;Shakeri,A.;Soleymani,L.;Didar,T.F.Hierarchical Structures,with Submillimeter Patterns,Micrometer Wrinkles,and Nanoscale Decorations,Suppress Biofouling and Enable Rapid Droplet Digitization.Small 2020,16(50),2004886.https: / / doi.org / 10.1002 / smll.202004886. (7)Yau,J.W.;Stafford,A.R.;Liao,P.;Fredenburgh,J.C.;Roberts,R.;Weitz,J.I.Mechanism of Catheter Thrombosis:Comparison of the Antithrombotic Activities of Fondaparinux,Enoxaparin,and Heparin in Vitro and in Vivo.Blood 2011,118(25),6667-6674.https: / / doi.org / 10.1182 / blood-2011-07-364141.

Claims

1. 1. A method for fabricating a material having a hierarchically structured surface, comprising: a) depositing a moldable polymer onto a mold containing microscale wrinkles and nanoscale features; b) curing the moldable polymer on the mold to provide a cured polymer; and c) removing the cured polymer from the mold to expose at least a structured surface of the cured polymer; A method comprising:

2. d) activating at least the surface of the cured polymer by oxidation; and e) coating at least a portion of the activated surface with lubricant tethering molecules to obtain at least one layer of lubricant tethering molecules on at least a portion of the activated surface of the cured polymer; The method of claim 1 further comprising:

3. The method of claim 2 , wherein coating the surface with the lubricant tethering molecules comprises chemical vapor deposition of the lubricant tethering molecules onto the surface.

4. The method of claim 2 , wherein the lubricant tethering molecule comprises a fluorosilane, a fluorocarbon, a fluoropolymer, an organosilane, a polysiloxane, or a mixture thereof.

5. 5. The method of claim 4, wherein the polysiloxane is formed using one or more compounds of formula II or the fluorosilane is selected from one or more compounds of formula I, preferably the fluorosilane comprises trichloro(1H,1H,2H,2H-perfluorooctyl)silane (TPFS). 【Chemical 1】 (In the formula, R ４ , R ５ and R ６ are each independently a hydrolyzable group; R ７ is C １～３０ alkyl) 【Chemistry 2】 wherein X is a single bond or C 1-6 alkylene; n is an integer from 0 to 12; and R 1 , R 2 and R 3 are each independently a hydrolyzable group.

6. further comprising, after said coating, depositing a lubricant layer on said at least one lubricant tethering molecule layer; wherein optionally, the lubricating layer comprises a hydrocarbon liquid, a fluorinated organic liquid, or a perfluorinated organic liquid, and preferably, the lubricating layer comprises perfluoroperhydrophenanthrene (PFPP); The method of claim 2.

7. The method of claim 2 , wherein activating at least the surface of the cured polymer comprises plasma treatment.

8. The method of claim 1 , wherein the template comprises a surface having a hierarchical structure of microscale wrinkles and nanoscale features, at least one layer of nanoparticles, and at least one layer of lubricant tethering molecules.

9. The method of claim 1 further comprising, after said depositing, subjecting said mold with said deposited moldable polymer to a vacuum.

10. the moldable polymer is an elastomeric polymer, an uncured elastomeric polymer, or a thermoplastic polymer; wherein optionally, the elastomeric polymer comprises a silicone elastomer, and preferably, the elastomeric polymer is polydimethylsiloxane (PDMS). The method of claim 1.

11. the material is flexible; the material is transparent, the material is repellent to liquids containing biospecies; the material is repellent to bacteria and biofilm formation; the material is repellent to biological fluids; the material is blood repellent; the material weakens coagulation, or a combination thereof is satisfied, The method of claim 2.

12. The method of claim 1 , wherein the material is not heat shrinkable, the moldable polymer is not heat shrinkable, or the cured polymer is not heat shrinkable.

13. A material comprising a surface with a hierarchical structure prepared using the method of any one of claims 1 to 12.

14. 14. A device or article comprising the material of claim 13, the material is on or forms the surface of the device or article; Device or article.

15. 14. A method for preventing, reducing, or delaying adhesion, adsorption, surface-mediated clot formation, or coagulation of biological material onto a device or article, comprising surface treating the device or article with the material of claim 13 to obtain a low-adhesion surface on the device or article.

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