The present invention relates to systems and methods for the manufacturing of microscale or nanoscale concentrically-layered fibers and other structures by electrospinning.
Macro-scale structures formed from concentrically-layered nanoscale or microscale fibers (“core-sheath fibers”) are useful in a wide range of applications including drug delivery, tissue engineering, nanoscale sensors, self-healing coatings, and filters. On a commercial scale, the most commonly used techniques for manufacturing core-sheath fibers are extrusion, fiber spinning, melt blowing, and thermal drawing. None of these methods, however, are ideally suited to producing drug-loaded core-sheath fibers, as they all utilize high temperatures which may be incompatible with thermally labile materials such as drugs or polypeptides. Additionally, fiber spinning, extrusion and melt-blowing are most useful in the production of fibers with diameters greater than ten microns.
Core-sheath fibers with diameters less than 20 microns can also be produced by electrospinning, in which an electrostatic force is applied to a polymer solution to form very fine fibers. Conventional electrospinning methods utilize a needle to supply a polymer solution, which, upon activation of an electric field, is then ejected into a continuous stream toward a grounded collector. As the jet stream travels in the air, solvent evaporation occurs resulting in a single long polymer fiber. Core-sheath fibers have been produced using emulsion-based electrospinning methods, which exploit surface energy to produce core-sheath fibers, but which are limited by the relatively small number of polymer mixtures that will emulsify, stratify, and electrospin. Core-sheath fibers have also been produced using coaxial electrospinning, in which concentric needles are used to eject different polymer solutions: the innermost needle ejects a solution of the core polymer, while the outer needle ejects a solution of the sheath polymer.
Coaxial electrospinning has been used in the fabrication of core-sheath fibers for drug delivery in which the drug-containing layer (the “core”) is confined to the center of the fiber and is surrounded by a drug-free layer (the “sheath”). The sheath then serves as a diffusion barrier to a therapeutic agent in the core. Thus, release rates of the drug can be tightly controlled by varying the thickness, composition, and degradation profile of the sheath material as well as composition and concentration of the drug in the core Additionally, core-sheath fibers can be used for tissue engineering (e.g., incorporation of therapeutics to affect cell growth), filtration (e.g., incorporation of self-cleaning compounds such as titania), sensors (e.g., creation of hollow fibers to allow measurement of small analyte volumes), and as self-healing materials (e.g., spontaneous repair of surfaces with release of core contents). Core-sheath fibers can also be used as a way to create fibers from materials that would be otherwise unable to be electrospun (e.g., polymer pre-cursors such as poly(glycerol sebacic acid) or insulating materials such as Teflon). To do so, the material incompatible with electrospinning is confined in the center of the fiber and is surrounded by a material optimized for electrospinning; upon completion of the process the surrounding sheath material is removed (e.g., dissolved or melted away).
However, the creation of core-sheath fibers using a single needle has limited throughput. To increase throughput, coaxial nozzle arrays have been utilized, but such arrays pose their own challenges, as separate nozzles may require separate pumps, the multiple nozzles may clog, and interactions between nozzles may lead to heterogeneity among the fibers collected. Another means of increasing throughput, which utilizes a spinning drum immersed in a bath of polymer solution, has been developed by the University of Liberec and commercialized by Elmarco, S.R.O. under the mark Nanospider®. The Nanospider® improves throughput relative to other electrospinning methods, but to date core-sheath fibers have not been fabricated using the Nanospider®. There is, accordingly, a need for a mechanically simple, high-throughput means of manufacturing core-sheath fibers.
The present invention addresses the need described above by providing systems and methods for high-throughput production of core-sheath fibers by co-localizing multiple materials to multiple sites of Taylor cone formation, promoting the formation of multiple electrospinning jets and electrospun fibers incorporating a plurality of materials.
In one aspect, the present invention relates to a device for high-throughput production of core-sheath fibers by electrospinning. The device comprises a hollow vessel having a slit therethrough (the “core slit”), through which a solution of the core polymer can be introduced; the device also includes one or more features for the introduction of a sheath polymer into, above, beneath, or alongside the core slit. In some embodiments, the device comprises an additional slit or slits abutting the core slit on one or both slides through which solutions of sheath polymer can be introduced. In some embodiments, the sheath solution is contained within a bath or other vessel in which the hollow vessel containing the core solution is immersed. In some embodiments, the vessel includes structural features such as channels or regions of texture or smoothness through which the sheath polymer solution can run.
In another aspect, the present invention relates to a device for collection of electrospun fibers in yarn form. The device comprises a grounded or oppositely charged collector for electrospun yarns, the collector being configured to rotate so that fibers are twisted into yarns as they are collected from an electrospinning apparatus.
In yet another aspect, the present invention relates to methods of making core-sheath fibers and electrospun yarns using the devices of the present invention.
In the drawings, like reference characters generally refer to the same parts throughout the different views. Drawings are not necessarily to scale, as emphasis is placed on illustration of the principles of the invention
The present invention relates to electrospun fibers, including drug-containing electrospun fibers and yarns described in co-pending U.S. patent application Ser. No. 12/620,334 (United States Publication No. 2010/0291182), the entire disclosure of which is incorporated herein by reference for all purposes.
An example of a fiber produced by the devices and methods of the present invention is shown schematically in
Examples of biodegradable polymers that can be used with this invention include: polyesters, such as poly(ε-caprolactonc), polyglycolic acid, poly(L-lactic acid), poly(DL-lactic acid); copolymers thereof such as poly(lactide-co-ε-caprolactone), poly(glycolido-co-ε-caprolactone), poly(lactide-co-glycolide), copolymers with polyethylene glycol (PEG); branched polyesters, such as poly(glycerol sebacate); poly(propylene fumarate); poly(ether esters) such as polydioxanone; poly(ortho esters); polyanhydrides such as poly(sebacic anhydride); polycarbonates such as poly(trimethylcarbonate) and related copolymers; polyhydroxyalkanoates such as 3-hydroxybutyrate, 3-hydroxyvalerate and related copolymers that may or may not be biologically derived; polyphosphazenes; poly(amino acids) such as poly (L-lysine), poly (glutamic acid) and related copolymers.
Examples, of biologically derived restorable polymers include: polypeptides such as collagen, elastin, albumin and gelatin; glycosaminoglycans such as hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate and heparin; chitosan and chitin; agarose; wheat gluten; polysaccharides such as starch, cellulose, pectin, dextran and dextran sulfate; and modified polysaccharides such as carboxymethylcellulose and cellulose acetate.
Examples of other dissolvable or resorbable polymers include polyethylene glycol and poly(ethylene glycol-propylene glycol) copolymers that are known as pluronics and reverse pluronics.
Examples of non-biodegradable polymers include: nylon 4, 6; nylon 6; nylon 6,6; nylon 12; polyacrylic acid; polyacrylonitrile; poly(benzimidazole) (PBI); poly(etherimide) (PEI); poly(ethylenimine); poly(ethylene terephthalate); polystyrene; poly(styrene-block-isobutylene-block-styrene); polysulfone; polyurethane; polyurethane urea; polyvinyl alcohol; poly(N-vinylcarbazole); polyvinyl chloride; poly (vinyl pyrrolidone); poly(vinylidene fluoride); poly(tetrafluoromethylene) (PTFE); polysiloxanes; and poly (methyl methacrylate).
Electrospun core-sheath fibers and other structures produced by the systems and methods of the invention may include any suitable drug, compound, adjuvant, etc. and may be used for any indication that may occur to one skilled in the art. In preferred embodiments, the drug or other material chosen is insoluble in the polymers and solvents comprising the core polymer solution, or the concentration of drug or material used exceeds the solubility limit of the drug or material in the polymers or solvents. Without limiting the foregoing, general categories of drugs that are useful include, but are not limited to: opioids; ACE inhibitors; adenohypophoseal hormones; adrenergic neuron blocking agents; adrenocortical steroids; inhibitors of the biosynthesis of adrenocortical steroids; alpha-adrenergic agonists; alpha-adrenergic antagonists; selective alpha-two-adrenergic agonists; androgens; anti-addictive agents; antiandrogens; antiinfectives, such as antibiotics, antimicrobials, and antiviral agents; analgesics and analgesic combinations; anorexics; antihelminthics; antiarthritics; antiasthmatic agents; anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals; antiemetic and prokinetic agents; antiepileptic agents; antiestrogens; antifiungal agents; antihistamines; antiinflammatory agents; antimigraine preparations; antimuscarinic agents; antinauseants; antineoplastics; antiparasitic agents; antiparkinsonism drugs; antiplatelet agents; antiprogestins; antipruritics; antipsychotics; antipyretics; antispasmodics; anticholinergics; antithyroid agents; antitussives; azaspirodecanediones; sympathomimetics; xanthine derivatives; cardiovascular preparations, including potassium and calcium channel blockers, alpha blockers, beta blockers, and antiarrhythmics; antihypertensives; diuretics and antidiuretics; vasodilators, including general coronary, peripheral, and cerebral; central nervous system stimulants; vasoconstrictors; hormones, such as estradiol and other steroids, including corticosteroids; hypnotics; immunosuppressives; muscle relaxants; parasympatholytics; psychostimulants; sedatives; tranquilizers; nicotine and acid addition salts thereof; benzodiazepines; barbiturates; benzothiadiazides; beta-adrenergic agonists; beta-adrenergic antagonists; selective beta-one-adrenergic antagonists; selective beta-two-adrenergic antagonists; bile salts; agents affecting volume and composition of body fluids; butyrophenones; agents affecting calcification; catecholamines; cholinergic agonists; cholinesterase reactivators; dermatological agents; diphenylbutylpiperidines; ergot alkaloids; ganglionic blocking agents; hydantoins; agents for control of gastric acidity and treatment of peptic ulcers; hematopoietic agents; histamines; 5-hydroxytryptamine antagonists; drugs for the treatment of hyperlipiproteinemia; laxatives; methylxanthines; monoamine oxidase inhibitors; neuromuscular blocking agents; organic nitrates; pancreatic enzymes; phenothiazines; prostaglandins; retinoids; agents for spasticity and acute muscle spasms; succinimides; thioxanthines; thrombolytic agents; thyroid agents; inhibitors of tubular transport of organic compounds; drugs affecting uterine motility; anti-vasculogenesis and angiogenesis; vitamins; and the like; or a combination thereof.
In certain alternate embodiments, multiple apparatuses 200 may be placed in rows comprising up to 50 units, either in parallel or end-to-end, with a preference for 10 or fewer units per row. An advantage of using multiple units versus one long unit for increased throughput is better control over the flow of the polymer solutions. Alternatively, multiple apparatuses may be placed in rows and operated via a central power supply and/or central polymer delivery system that distributes an electric voltage and polymer solution to multiple individual apparatuses.
The core polymer solution 230 preferably has a viscosity of between 1 and 100,000 centipoise, and is more preferably between 200 and 5,000 centipoise. Core polymer solution 230 is preferably pumped through the lumen of tube 210 and slit 220 at rates of between 0.01 and 1000 milliliters per hour per centimeter, more preferably between 5 and 200 milliliters per hour per centimeter. A voltage, preferably between 1 and 250 kV, more preferably between 20-100 kV, is applied. The positive electrode of the power supply is preferably connected to the conducting slit-cylinder directly or via a wire, such that a potential difference exists between the slit cylinder and a grounded collector 250. Grounded collector 250 is preferably placed at a distance between 1 and 100 centimeters from slit 220 and parallel to the axial dimension of tube 210. Grounded collector 250 consists of various geometries (e.g. rectangular, circular, triangular, etc.), rotating drum/rod, wire mesh, air gaps, or other 3D collectors including spheres, pyramids, etc. In alternate embodiments the collector is oppositely charged relative to the polymer solution(s). In some embodiments, the collector 250 includes one or more grounded or oppositely charged points (for example, two grounded points separated by a space), and fibers collect around the one or more points and/or between them. Upon application of a sufficient voltage, Taylor cones 240 and electrospinning jets 241 will form at the exposed surface of core polymer solution 230, and the jets will attract toward collector 250, forming homogeneous fibers.
The invention includes means for co-localizing sheath and core polymer solutions at multiple sites of Taylor cone formation so that core-sheath fibers are produced. In certain embodiments, devices of the invention comprise a hollow vessel having a lengthwise slit therethrough, through which a solution of the core polymer can be introduced. The devices additionally comprise two slits abutting the core slit on both slides through which solutions of the sheath polymer are supplied. Flow of both core and sheath polymer solutions is initiated and an electric field is introduced. These steps are performed in any suitable order: for example, in some embodiments, flow of the core polymer solution is initiated, a field is introduced and Taylor cones and electrospinning jets comprising core polymer solution are formed; then sheath polymer flow is initiated such that the sheath polymer is incorporated into Taylor cones and electrospinning jets. In other embodiments, the sheath polymer flow is initiated first, then the field is introduced and, after formation of Taylor cones and electrospinning jets, the core polymer flow is initiated. In still other embodiments, both polymer solutions are provided simultaneously, then the field is introduced, etc.
Application of an electric field of sufficient strength to apparatuses of the invention leads to formation of Taylor cones and electrospinning jets in the polymer solution or solutions. In some embodiments, Taylor cones and electrospinning jets are formed in the core polymer solution 230, then the sheath polymer solution 260 is added alongside or above the core polymer solution 230 so that the sheath polymer solution 260 is drawn up into Taylor cones 240 and electrospinning jets 241. In preferred embodiments, Taylor cones and jets are formed in the sheath polymer solution 260 and the core polymer solution 230 is added, preferably beneath the sheath polymer solution 260, so that it is incorporated or pulled into electrospinning jets. As illustrated in
In alternate embodiments of the present invention, three parallel troughs are utilized, as illustrated in
In certain alternate embodiments, such as that illustrated in
In certain alternate embodiments, as illustrated in
While the bath is depicted in
In other embodiments, such as the one described in Example 2, infra, the sheath polymer solution 260 can be introduced directly to the sites of Taylor cone and jet initiation 240, 241, by using a syringe pump and needle. This method is superior to previously used coaxial nozzle arrays, as single bore needles are used, reducing the likelihood of clogging.
In an alternate embodiment, the invention comprises a collector plate configured as a drum 400, which can be placed into a yarn-spinning apparatus as shown in
The structural uniformity of core-sheath fibers produced by the apparatuses and methods of the invention depends in part upon the supply of core polymer solution 230 and sheath polymer solution 260 to the interior and exterior of the hollow tube 210. Without wishing to be bound to any theory, it is believed that supplying fluid evenly over time and across the width of the slit permits the fluid surface exposed to the electrical field to be kept relatively even and flat and to prevent variations in electrical field strength across the long axis of the slit over time (except for electrical field variations originating from electrospinning jet formation). In certain embodiments of the invention, the evenness of fluid flow is reflected, among other ways, in the evenness of the meniscus within the slit or other elongate area in which Taylor cones or electrospinning jets 240, 241 form.
In preferred embodiments, core and/or sheath polymer solutions 230, 260 are provided to the interior and exterior of the hollow tube 210 at the slit 220 in a steady, laminar fashion such that fluid velocity and pressure of the core and/or sheath polymers 230, 260 are constant across the width of the slit 230 over time. Such steady, laminar flow can be achieved by a variety of methods, which may be used alone or combined, and the inventors have found that driving polymer flow pneumatically, hydraulically, mechanically (piston-driven) or by gravity can result in a suitably consistent supply of the required fluids; this aim can also be met by employing flow directing structures such as diffusers in flow paths for the core and sheath polymers 230, 260
With respect to pneumatic driving of fluids,
Any suitable gas may be used to drive the flow of core and/or sheath fluids 230, 260, including air, but in preferred embodiments a non-reactive or inert gas is used such as Nitrogen, Helium, Argon, Krypton, Xenon, Carbon dioxide, Helium, Nitrous Oxide, Oxygen combinations thereof and the like. The gas used to drive flows is optionally insoluble in the solvents used in the core or sheath polymer solutions 230, 260 to prevent the formation of gas bubbles during electrospinning. Additional steps may be taken to prevent bubble formation during electrospinning, including de-gassing the core and sheath polymer solutions 230, 260 prior to use and separating the gas used to drive fluid flows from the polymer solutions 230, 260 through the use of an impermeable membrane or piston. In some embodiments, an inflatable balloon is used to displace polymer solutions 230, 260 from the reservoirs 231, 261. The reservoirs 231, 261 and the gas inputs 280 are preferably sufficiently airtight to prevent leakage at the gas pressures used.
As shown in
With respect to hydraulic driving of fluids, as shown in
In some embodiments, the piston includes one or more sealing features 286 such as gaskets or O-rings to prevent the driving fluid from mingling with the polymer solution. This aim may also be achieved in some embodiments by tailoring the surfaces of the piston 285 and/or the reservoir to repel the fluid 281 used to drive the piston 285—for example, in embodiments where water is used to drive the piston 285, the piston and the wall of the reservoir may include hydrophobic surfaces to prevent the migration of water past the piston.
With respect to piston-driven fluids, piston 285 may be made of any suitable material, including plastics, metals and combinations thereof. In some embodiments, the piston 285 is made of a material that is the same as or similar to a material included in the hollow tube 210; in other embodiments, the piston is non-conductive and/or includes a dielectric material. The piston preferably includes a material that is non-reactive with the polymer solutions 230, 260. The piston and/or the reservoir may include a coating or surface to render it non-reactive and/or to prevent a gas or liquid used to drive the piston from mingling with the polymer solution. The piston and/or the reservoir may also include a coating to minimize friction between the piston and the walls of the reservoir to prevent binding between the piston to the walls and variation in fluid velocities and pressures delivered to the slit 220.
Pistons may be driven pneumatically, hydraulically (as discussed above) or by mechanical actuators such as screw actuators or linear actuators. Multiple pistons may be used to drive core polymer solution 230 and sheath polymer solution 260. As shown in
Pressure diffusers can be used to even out flow across a vessel and/or a slit for electrospinning. Pressure diffusers, as the term is used herein, refers to structures that obstruct at least a portion of a flow path to re-direct a relatively narrow stream of fluid over a larger area. A pressure diffuser may include holes, slits, or other apertures to permit fluid to flow through the diffuser. A diffuser may also include angled, curved, or beveled surfaces to force fluid contacting such surfaces to flow in desired directions around the diffuser. One or more diffusers can be arranged, in parallel or in series, across a flow path to more fully diffuse the flow of a solution. The diffuser can include surfaces parallel to, perpendicular to, or otherwise angled to a desired direction of flow. A selection of diffusers compatible with the invention are illustrated in
With respect to gravity-driven fluid flows, in such embodiments, a reservoir such as a core polymer solution reservoir 231 will be positioned above the hollow tube 210 and the slit 220, such that the polymer solution 230/260 will flow downward by gravity from the reservoir toward the slit. The apparatus 200 includes a vent or valve through which air can enter the reservoir 231/261 to occupy space vacated by polymer solution 230/260 as it flows toward the slit 220.
In some embodiments, the polymers used in the present invention include additives such as drug particles, metallic or ceramic particles to yield fibers having a composite structure.
Although the disclosure herein has focused on linear vessels having linear slits, any suitable geometry may be used, including round designs as shown in
In addition, although the disclosure focuses on systems and methods utilizing a single lengthwise slit, any suitable aperture geometry may be used, including without limitation multiple short slits, holes, curved slits, slits and holes together, etc. Similarly, the invention includes systems and methods utilizing complex three-dimensional arrangements, such as that shown in
Preferred embodiments of the invention utilize elongate areas including slits for electrospinning. Using elongate areas rather than, say, radially symmetrical or square areas advantageously permits multiple solutions or materials to be continuously and evenly supplied to sites of Taylor cone and electrospinning jet formation such that they are closely opposed, yet remain separate. In non-elongate areas such as squares, Taylor cones and electrospinning jets that form in the center of the area tend to deplete the supply of materials or polymer solutions in the center of the area, which materials cannot be replaced as efficiently and evenly while remaining in an unmixed fashion as is possible in narrower, more elongate areas. In addition, the use of elongate areas provides a straightforward path to scaling-up fiber production: as the long dimension of the elongate area increases, it is possible to form more Taylor cones and electrospinning jets within the area, yet by keeping a short dimension relatively constant, materials and polymer solution can be rapidly supplied from alongside or underneath the area to prevent depletion. Suitable dimensions for slits in apparatuses of the invention are disclosed in Examples 7 and 8, below.
The systems and methods described herein can be adapted to form structures other than core-sheath fibers. For example, core-sheath particles may be formed using core and/or sheath polymer solutions with low viscosity. Upon introduction on an electric field, Taylor cones and structures similar to electrospinning jets (which are referred to as “spray jets” herein) will form. Due to the low viscosity of the solutions, the spray jets will break-up midstream leading to particle formation. Optionally, vibration can be used to disrupt the flow of the core and/or sheath solutions to further encourage the formation of spray jets and/or particles.
The invention also includes combinations of the systems and methods described above. For example, structures incorporating multiple sheath polymers can be formed using a vessel/bath setup as described above in combination with a syringe pump to provide a second sheath polymer solution to sites of Taylor cone formation.
In some embodiments, one or more of the core polymer solution and the sheath polymer solution is delivered in a pulsatile manner to create fibers with gradients of core densities and/or sheath thicknesses.
The invention includes systems and methods in which limited or no structure is used to separate core and sheath polymer solutions 220, 260. As shown in
The devices and methods of the present invention may be further understood according to the following non-limiting examples:
To illustrate the principle by which multiple Taylor cones and electrospinning jets are generated by the systems and methods of the invention, homogeneous fibers made of poly(lactic co-glycolic acid) (L-PLGA) were manufactured in accordance with the present invention. A solution containing 4.5 wt % of 85/15 L-PLGA in hexafluoroisopropanol was pumped into one end of a 10 cm long hollow tube (1 cm diameter) having a 0.4 cm slit of the present invention at a rate of 8 milliliters per hour. A grounded, flat, rectangular collecting plate was placed approximately 15 centimeters from the slit of the cylinder, and a voltage of 25-35 kV was applied, and the resultant fibers were collected on the collecting plate and examined under scanning electron microscopy as illustrated in
Core-sheath fibers were manufactured in accordance with the present invention, as shown in
Slit-surfaces of various geometries were fabricated and the formation of electrospinning jets from these surfaces was demonstrated.
Even flow of polymer solution to a slit was achieved by the use of a mechanical piston.
Even flow of polymer solution to the slit was achieved by incorporating pressure diffusers to divert momentum of fluid flow across the slit. Shown in
Another method for even flow can be achieved by redirecting polymer solution to flow in the opposite direction of initial direction. Shown in
Core-sheath fibers were manufactured using an apparatus according to the embodiment of
A sheath solution 260 of 2.8 wt % 85/15 PLGA in 6:1 (by vol) chloroform/methanol and a core solution 230 of 2.8 wt % 85/15 PLGA in 6:1 (by vol) chloroform/methanol containing 30% wt % dexamethasone drug with respect to PLGA was used. The sheath flow rate was set at 100 ml/h while the core flow rate was set at 50 ml/h. A voltage of 50 kV was applied.
Core-sheath fibers were manufactured using an apparatus according to the embodiment of
Fibers with various core-sheath structures were fabricated using an apparatus according to the embodiment of
An apparatus incorporating a round slit rather than a linear one has been used. A showerhead fixture was modified, replacing a center piece with a plug to form a circumferential slit. When a 1 wt % PLGA solution was provided to the slit, multiple Taylor cones and electrospinning jets were observed, as shown in
The term “and/or” is used throughout this application to mean a non-exclusive disjunction. For the sake of clarity, the term A and/or B encompasses the alternatives of A alone, B alone, and A and B together. The aspects and embodiments of the invention disclosed above are not mutually exclusive, unless specified otherwise, and can be combined in any way that one skilled in the art might find useful or necessary.
The term “elongate” is used throughout this application to refer to structures having at least two dimensions, one dimension being longer, and preferably substantially longer, than the other(s). For the sake of clarity, the term “elongate” encompasses structures that are linear, cylindrical, cuboidal, curved, curvilinear, toroidal, annular, angled, rectangular, etc. and any structure that could be formed by bending or curving one of the elongate structures listed above.
While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the functions and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the scope of the present invention.
The breadth and scope of the invention is intended to cover all modifications and variations that come within the scope of the following claims and their equivalents:
This application is a Continuation of U.S. patent application Ser. No. 13/362,467 entitled “Electrospinning Process for Fiber Manufacture”, filed Jan. 31, 2012, which claims priority to U.S. Provisional Application No. 61/437,886 entitled “Electrospinning Process for Fiber Manufacture” by Quynh Pham et al., filed Jan. 31, 2011.
Number | Date | Country | |
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61437886 | Jan 2011 | US |
Number | Date | Country | |
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Parent | 13362467 | Jan 2012 | US |
Child | 14637305 | US |