Patent Abstract:
Devices and methods for high-throughput manufacture of concentrically layered nanoscale and microscale fibers by electrospinning are disclosed. The devices include a hollow tube having a lengthwise slit through which a core material can flow, and can be configured to permit introduction of sheath material at multiple sites of Taylor cone formation formation.

Full Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to systems and methods for the manufacturing of microscale or nanoscale concentrically-layered fibers by electrospinning 
       CROSS REFERENCE TO RELATED APPLICATIONS 
       [0002]    The present invention claims priority to U.S. Provisional Application No. 61/437,886 entitled “Electrospinning Process for Fiber Manufacture,” filed Jan. 31, 2011; and to U.S. application Ser. No. 13/362,467 entitled “Electrospinning Process for Manufacture of Multi-Layered Structures,” filed Jan. 31, 2012. 
       BACKGROUND 
       [0003]    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. 
         [0004]    Core-sheath fibers can 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 charged needle to supply a polymer solution, which is then ejected in a continuous stream toward a grounded collector. After removal of solvents by evaporation, a single long polymer fiber is produced. 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. This method is particularly useful for fabrication of core-sheath fibers for drug delivery in which the drug-containing layer is confined to the center of the fiber and is surrounded by a drug-free layer. However, both emulsion and coaxial electrospinning methods can have relatively low throughput, and are not ideally suited to large-scale production of core-sheath fibers. 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 it is not currently possible to manufacture core-sheath fibers using the Nanospider®. There is, accordingly, a need for a mechanically simple, high-throughput means of manufacturing core-sheath fibers. 
       SUMMARY OF THE INVENTION 
       [0005]    The present invention addresses the need described above by providing a system and method for high-throughput production of core-sheath fibers. 
         [0006]    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 tube having a lengthwise slit therethrough, which can be filled with a solution of the core polymer, and optionally includes a bath in which the hollow tube is immersed, which can be filled with a solution of the sheath polymer. The tube also optionally includes structural features such as channels or regions of texture or smoothness through which the sheath polymer solution can run. In an alternate embodiment, the device comprises three adjacent troughs arranged so that two external troughs sandwich a central trough. The central trough is filled with a solution of the core polymer, while the external troughs are filled with solutions of the sheath polymer. 
         [0007]    In another aspect, the present invention relates to a device for collection of electrospun fibers in yarn form. The device comprises a grounded 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. 
         [0008]    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. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]    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 
           [0010]      FIG. 1A-1D  show schematic illustrations of a fiber generated by the present invention. 
           [0011]      FIG. 2  is a schematic illustration of a portion of an electrospinning apparatus according to an embodiment of the invention. 
           [0012]      FIG. 3A-3B  show schematic illustrations of a portion of an electrospinning apparatus according to an embodiment of the invention. 
           [0013]      FIG. 4A-4B  show schematic illustrations of a portion of an electrospinning apparatus according to another embodiment of the invention. 
           [0014]      FIG. 5A-5B  show schematic illustrations of a portion of an electrospinning apparatus according to yet another embodiment of the invention. 
           [0015]      FIG. 6  is a schematic illustration of a yarn-making apparatus according to an embodiment of the invention. 
           [0016]      FIG. 7A-7B  comprise photographs of an example of the present invention. 
           [0017]      FIG. 8A-8B  show photographs of another example of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0018]    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. 20100291182), the entire disclosure of which is incorporated herein by reference. 
         [0019]    An example of a fiber produced by the devices and methods of the present invention is shown schematically in  FIGS. 1   a  and  1   b.  Fiber  100  is generally tubular in shape, and is characterized by a length  110  and a diameter  111 . Fibers generated by the devices and methods of the present invention are generally small enough to be useful for implantation to address a wide range of medical applications. As such, the fiber  100  has a diameter that is preferably up to about 20 microns. The length  110  of fiber  100  will vary depending on its intended use, and may range widely from micrometers to centimeters or greater. In a preferred embodiment, fiber  100  includes an inner radial portion  120  and an outer radial portion  130 , as shown in  FIGS. 1   c  and  1   d.  In this preferred embodiment, the total diameter  111  of the fiber is no more than about 20 microns, and the diameter of the outer radial portion is about 1-7 microns larger than the inner radial portion. 
         [0020]      FIG. 2  illustrates one embodiment of the present invention. Apparatus  200  comprises a hollow cylindrical tube  210  having a longitudinal slit  220  along its entire length. A core polymer solution  230  can be introduced into the lumen of tube  210  in a volume sufficient for the surface of the solution to emerge through slit  220 . In one example, tube  210  is 0.5-20 cm in diameter with a wall thickness of 50-5,000 microns. The cylindrical tube  210  is made of a conducting material such as stainless steel, copper, bronze, brass, gold, silver, platinum, and other metals and alloys. Slit  220  preferably has a width sufficient to permit formation of Taylor cones  240  from the surface of the core polymer solution  230 , the width of slit  220  being generally between 0.01 and 20 millimeters, and preferably between 0.1 to 5 millimeters. The length of tube  210  is preferably between 5 centimeters and 50 meters, and more preferably between 10 centimeters and 2 meters. 
         [0021]    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 is better control over the flow of the polymer solutions. 
         [0022]    The core polymer solution  230  preferably has a viscosity of between 10 and 10,000 centipoise, and is more preferably between 500 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 10 milliliters per hour, more preferably between 0.1 and 2 milliliters per hour per centimeter. A voltage, preferably between 1 and 150 kV, more preferably between 20-70 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  is a planar plate of various geometries (e.g. rectangular, circular, triangular, etc.), rotating drum/rod, wire mesh, or other 3D collectors including spheres, pyramids, etc. Upon application of a sufficient voltage, Taylor cones  240  and electrospinning jets  241  will form in the exposed surface of polymer solution  230 , and the jets will flow toward collector  250 , forming homogeneous fibers. 
         [0023]    In certain embodiments of the present invention, the apparatus will include means for co-localizing a sheath polymer solution to the site of Taylor cone initiation, so that core-sheath fibers can be produced. In certain embodiments, such as that illustrated in  FIG. 3 , hollow cylindrical tube  210  will be arranged so that slit  220  points downward, and a sheath polymer solution  260  will be applied to the upward-facing external surface of tube  210  so that sheath polymer solution  260  runs down the sides of tube  210  and co-localizes with the core-sheath polymer at sites of Taylor cone and jet initiation  240 ,  241 . Once the sheath polymer solution  260  is co-localized with the Taylor cone, it will be incorporated into the jet. The sheath polymer solution  260  is drawn toward and over the core fibers by varying the flow rate and viscosity of the sheath polymer solution  260 , or by incorporating structural features  211  such as grooves, channels, coatings, and textured or smooth surfaces on the outer surface of hollow tube  210 . 
         [0024]    In certain alternate embodiments, as illustrated in  FIG. 4 , hollow tube  210  will be partially submerged in a bath  270  containing the sheath polymer solution  260 . The volume of the sheath polymer solution  260  within bath  270  will be set at a level so that the top surface of the sheath polymer solution is at or near the sites of Taylor cone and jet initiation  240 ,  241 . As described above, the rate at which sheath polymer solution  260  is drawn into fibers can be controlled by varying the viscosity of sheath polymer solution  260 , or by incorporating structural features  211  on the outer surface of hollow tube  210  such as grooves, channels, coatings and textured or smooth surfaces. 
         [0025]    In still other alternate 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 preferred over previously used coaxial nozzle arrays, as single bore needles are used, reducing the likelihood of clogging. 
         [0026]    In an alternate embodiment of the present invention, three parallel troughs are utilized, as illustrated in  FIG. 5 . Apparatus  300  comprises an inner trough  310  and two outer troughs  320 ,  330 . The walls  311 ,  312  of inner trough  310  are optionally tapered, so that their thickness decreases to zero at the top of inner trough  310 . Inner trough  310  is filled with a solution of core polymer solution  220 , which is pumped through inner trough  310  from the bottom up at rates suitable for electrospinning, generally between 0.1 to 2 milliliters per hour per centimeter, but up to 10 milliliters per hour per centimeter. Alternatively, the solution can be fed in from the sides or a combination of the bottom and sides. Inner trough  310  has a height ranging preferably from 5-10 centimeters and a width sufficient to permit formation of Taylor cones and jets  240 ,  241 , which emerge from the surface of core polymer solution  220 , the width of inner trough  310  being generally between 0.01 and 20 millimeters, and preferably between 0.1 to 5 millimeters. Outer troughs  320 ,  330  are filled with sheath polymer solutions  260  to heights sufficient for the sheath polymer solution to be drawn into the sites of Taylor cone and jet initiation  240 ,  241 . As shown in  FIG. 5   b , walls  311 ,  312  of inner trough  310  may incorporate a reciprocal periodic wave structure, forming regions of higher and lower width within inner trough  310 , which structure biases the formation of Taylor cones and jets  240 ,  241  to regions in which the width of inner trough is locally maximized. The voltage is applied by attaching the positive electrode of the power supply to the inner walls of the trough, which is composed of a metallic conducting material such as stainless steel, copper, bronze, gold, silver, platinum and other alloys. 
         [0027]    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  FIG. 6 . At any point during collection of fibers (prior to initiation, during collection, or after collection initiation), the drum is engaged with a belt that is in turn engaged with a mandrel that can spin in one direction, and free ends of the collected fibers are attached to another drum engaged with another belt that is engaged with a different mandrel which spins in a direction opposite from that of the first mandrel. The resulting yarns can be post-processed into higher-order structures such as ropes by attaching opposite ends of multiple yarns to opposing drums, and spinning them in opposite directions as described above. 
         [0028]    In some embodiments of the invention, the polymers used in the present invention include additives such as metallic or ceramic particles to yield fibers having a composite structure. 
         [0029]    The devices and methods of the present invention may be further understood according to the following non-limiting examples: 
       Example 1 
     Formation of Homogeneous Fibers 
       [0030]    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  FIG. 7   b.    
       Example 2 
     Formation of Core-Sheath Fibers 
       [0031]    Core-sheath fibers were manufactured in accordance with the present invention, as shown in  FIG. 8   a . A rhodamine-containing core solution containing 15 wt % polycaprolactone in a 3:1 (by volume) chloroform:acetone solution was pumped through a hollow cylindrical tube having a slit therethrough at a rate of 10 ml/hour. Jets were formed by applying a voltage of 25 kV. Once the Taylor cones were stable, a syringe pump and needle filled with a fluorescein-containing sheath solution containing 15 wt % polycaprolactone in a 6:1 (by volume) chloroform:methanol solution was placed so that the needle was adjacent to one of the Taylor cones, and the sheath solution was pumped at a rate of 6 ml/hour. To verify the core-sheath structure of the resulting fibers, fluorescence micrographs were obtained which demonstrated that the rhodamine-containing core component was indeed surrounded by the fluorescein-containing sheath component, as shown in  FIG. 8   b.    
         [0032]    The present invention provides devices and methods for producing homogeneous and core-sheath fibers. While aspects of the invention have been described with reference to example embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention.

Technology Classification (CPC): 3