Patent Publication Number: US-2022211989-A1

Title: Microneedle array assembly and fluid delivery apparatus having such an assembly

Description:
FIELD OF THE DISCLOSURE 
     The present disclosure relates generally to a fluid delivery apparatus, and more particularly to a microfluidic distribution manifold for use with a microneedle assembly of the fluid delivery apparatus. 
     BACKGROUND OF THE DISCLOSURE 
     Numerous apparatus have been developed for transdermal delivery of medicines using microneedle assemblies. Microneedle assemblies facilitate reducing an amount of pain felt by a patient as compared to larger conventional needles. Conventional subcutaneous (and often intra-muscular) delivery of medicines using a needle operates to deliver a large quantity of the medicine at one time, thereby creating a spike in the bioavailability of the medicine. While this is not a significant problem for some medicines, many medicines benefit from having a steady state concentration in the patient&#39;s blood stream. Transdermal delivery apparatus are capable of slowly administering drugs at a substantially constant rate over an extended period of time. However, the quantity of the medicine delivered through each microneedle of the microneedle assembly may not be equal. Alternatively, transdermal drug delivery apparatus may administer drugs at variable rates. Thus, transdermal drug delivery apparatus offer several advantages relative to conventional subcutaneous drug delivery methods. 
     BRIEF DESCRIPTION 
     In one aspect, a microneedle array assembly is provided. The microneedle array assembly includes a microneedle array including a plurality of microneedles, and a distribution manifold including a supply channel. The supply channel is coupled in flow communication to a plurality of resistance channels. Each resistance channel is coupled in flow communication to a respective one of the plurality of microneedles. A resistance value to a fluid flow through each resistance channel of the plurality of resistance channels is in the range between about 5 times greater to about 100 times greater than a resistance to the fluid flow through the supply channel. 
     In another aspect, a fluid delivery apparatus is provided. The fluid delivery apparatus includes a reservoir containing a fluid, and a microneedle array assembly. The microneedle array assembly includes a microneedle array having a plurality of fluid channels formed in an upstream side, and a plurality of a plurality of microneedles extending from a downstream side. Each microneedle is coupled in flow communication to a respective one of the plurality of fluid channels. The microneedle array also includes a distribution manifold having a supply channel coupled in flow communication to the plurality of fluid channels. A resistance value to a fluid flow through each fluid channel of the plurality of fluid channels is in the range between about 5 times greater to about 100 times greater than a resistance to the fluid flow through the supply channel. 
     In yet another aspect, a microneedle array assembly is provided. The microneedle array assembly includes a microneedle array having a plurality of microneedles. Each microneedle of the plurality of microneedles includes an aperture. The microneedle array also includes a distribution manifold having an inlet channel, a plurality of supply channels formed in a downstream surface of the distribution manifold, and a plurality of outlet channels. Each of the supply channels is coupled in flow communication to the inlet channel and a respective one of the plurality of outlet channels. A pressure drop between the inlet channel and each outlet channel of the plurality of outlet channels is substantially the same. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       These and other features, aspects, and advantages of the present disclosure will become better understood when the following detailed description is read with reference to the accompanying drawings in which like characters represent like parts throughout the drawings, wherein: 
         FIG. 1  is a sectional view of an exemplary fluid delivery apparatus; 
         FIG. 2  is a sectional view of a cartridge and a mechanical controller of the fluid delivery apparatus shown in  FIG. 1 ; 
         FIG. 3  is an exploded schematic of an exemplary microneedle array assembly for use with the fluid delivery apparatus shown in  FIG. 1 ; 
         FIG. 4  is a schematic cross-sectional view of the microneedle array assembly of  FIG. 3 ; 
         FIG. 5  is a schematic plan view of a distribution manifold for use with the microneedle array of  FIG. 3 ; 
         FIG. 6  is a sectional view of the distribution manifold taken about line A-A, illustrating an exemplary profile of a supply channel; 
         FIG. 7  is a representation of a portion of the microneedle array assembly and the resistance to a fluid flow therein; 
         FIG. 8  is an exploded schematic of another exemplary microneedle array assembly for use with the fluid delivery apparatus shown in  FIG. 1 ; 
         FIG. 9  is an enlarged, partial schematic cross-sectional view of the microneedle array assembly of  FIG. 8 ; 
         FIG. 10  is a schematic plan view of a back surface of the microneedle array for use with the microneedle array assembly of  FIG. 8 , including a distribution manifold; 
         FIG. 11  is an exploded schematic of another exemplary microneedle array assembly for use with the fluid delivery apparatus shown in  FIG. 1 ; 
         FIG. 12  is an enlarged, partial schematic cross-sectional view of the microneedle array assembly of  FIG. 11 ; and 
         FIG. 13  is a schematic plan view of a back surface of a distribution manifold for use with the microneedle array assembly of  FIG. 11 . 
     
    
    
     Unless otherwise indicated, the drawings provided herein are meant to illustrate features of embodiments of the disclosure. These features are believed to be applicable in a wide variety of systems comprising one or more embodiments of the disclosure. As such, the drawings are not meant to include all conventional features known by those of ordinary skill in the art to be required for the practice of the embodiments disclosed herein. 
     DETAILED DESCRIPTION 
     In the following specification and the claims, reference will be made to a number of terms, which shall be defined to have the following meanings. The singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements. “Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event occurs and instances where it does not. 
     Approximating language, as used herein throughout the specification and claims, may be applied to modify any quantitative representation that could permissibly vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term or terms, such as “about,” “approximately,” and “substantially,” are not to be limited to the precise value specified. In at least some instances, the approximating language may correspond to the precision of an instrument for measuring the value, Here and throughout the specification and claims, range limitations may be combined and/or interchanged; such ranges are identified and include all the sub-ranges contained therein unless context or language indicates otherwise. 
     As used herein, positional terms such as upward, downward, upper, lower, top, bottom, and the like are used only for convenience to indicate relative positional relationships. 
     Referring now to the drawings,  FIG. 1  is a sectional view of an exemplary fluid delivery apparatus  10  (e.g., a drug delivery apparatus). In the exemplary embodiment, the fluid delivery apparatus  10  includes a plurality of subassembly components coupled together to form the fluid delivery apparatus  10 , including a receptacle  12 , a cartridge  14 , and a mechanical controller  16 . Each of the receptacle  12 , the cartridge  14 , and the mechanical controller  16  is indicated generally in the accompanying drawings. The receptacle  12 , as seen in  FIG. 1 , forms the body of the fluid delivery apparatus  10  and is slidably coupled to the cartridge  14 . In addition, the mechanical controller  16 , as explained in more detail below, is coupled to the cartridge  14 . 
     In the exemplary embodiment, the receptacle  12  includes an outer body  18  formed in a generally frustoconical shape and having an interior space  20  defined therein. The outer body is formed substantially symmetrically about a central axis “A.” An upper rim  22  of the body  18  defines an opening  24  to the interior space  20 . An inner surface  26  extends generally vertically downward from the rim  22  towards a base wall  28  of the body  18  and extends around the interior space  20 . As illustrated in  FIG. 1 , the outer body  18  includes a curved outer surface  30  that is generally inclined inward as it extends upward from the base wall  28  to the rim  22 . A notch  32  extends around the interior space  20  and is formed at an intersection of the inner surface  26  and the base wall  28 . The notch includes and generally vertical outer wall  34  and a generally horizontal upper wall  36 . 
     In the exemplary embodiment, the receptacle  12  further includes a controller support structure  40  coupled to the body  18  within the interior space  20 , and a microneedle array support structure  42  coupled to the notch  32  of the body  18 . In addition, the controller support structure  40  is coupled to the microneedle array support structure  42 . 
     The controller support structure  40  includes a lower annular wall portion  44  that extends vertically downward beyond the horizontal upper wall  36  of the notch  32 . The lower wall portion  44  includes a flange portion  46  that extends radially outward from the lower wall portion  44  and is configured to engage the horizontal upper wall  36  of the notch  32 . The flange portion  46  includes a plurality of latch members  56  configured to engage and couple to at least a portion of microneedle array support structure  42 . At an upper wall portion  48 , the controller support structure  40  includes an inner beveled surface  50  and a plurality of spaced flexible tabs  52  that extend radially inward from the inner surface  26  of the body  18 . Each of the flexible tabs  52  includes an inward extending protrusion  54  at the free end of the flexible tab. The inward extending protrusions  54  are configured to engage the cartridge  14 . 
     In the exemplary embodiment, the microneedle array support structure  42  includes a generally planar body portion  60  that extends horizontally across the interior space  20  of the body  18 . A peripheral wall  62  extends vertically upward about a periphery of the body portion  60  and includes and outer surface  64  configured to engage the vertical outer wall  34  of the notch  32 . In particular, the peripheral wall  62  is formed substantially parallel to the vertical outer wall  34  and is sized to couple to the vertical outer wall  34  via an interference fit. As used herein, the phrase “interference fit” means a value of tightness between the vertical outer wall  34  and the peripheral surface  60 , i.e., an amount of radial clearance between the components. A negative amount of clearance is commonly referred to as a press fit, where the magnitude of interference determines whether the fit is a light interference fit or an interference fit. A small amount of positive clearance is referred to as a loose or sliding fit. 
     The microneedle array support structure  42  also includes a vertically upward extending central wall  66  located proximate a central portion of the body portion  60 . As illustrated in  FIG. 1 , the central wall  66  includes an upper rim  68  configured to couple to the cartridge  14 . The microneedle array support structure  42  also includes a frame portion  70  that extends vertically downward from the body portion  60 . The frame portion  70  defines a mounting space  72  for coupling a microneedle array assembly  80  to a mounting surface  74  located within the mounting space  72 . 
     In addition, with continued reference to  FIG. 1 , the microneedle array support structure  42  includes at least one cannula  82  coupled to a mount  84  extending upward from the microneedle array support structure  42 . In particular, a lower portion of the cannula  82  is coupled in fluid communication with a fluid passage  86  extending through the microneedle array support structure  42  via an interference fit with the mount  84 . Alternatively, the cannula  82  may be coupled to the mount  84  using any suitable fastening technique, for example, adhesive bonding, that enables the microneedle array support structure  42  to function as described herein. In the exemplary embodiment, an upper portion the cannula  82  is sharply pointed and extends upward away from the microneedle array support structure  42 , such that the cannula  84  can pierce a portion of the cartridge  14 . As illustrated, the cannula  82  extends upward through a sealing gasket  88  coupled to the mount  84  and configured to seal the fluid passage  86 . 
     In the exemplary embodiment, the microneedle array support structure  42  includes a protective release paper backing  90  extending substantially entirely over an adhesive layer  92  that is coupled to the base wall  28  of the body  18  and at least a portion of the lower surface of the microneedle array support structure  42 . The adhesive layer  92  is configured to couple the fluid delivery apparatus  10  to a user&#39;s skin surface. The release paper backing  90  is configured to prevent the adhesive layer  92  from coupling to the user, or any other object, before use of the fluid delivery apparatus  10 . 
       FIG. 2  is a sectional view of the cartridge  14  and the mechanical controller  16  of the fluid delivery apparatus  10  shown in  FIG. 1 . In the exemplary embodiment, the cartridge  14  includes a central body  100  having central axis “A.” The central body  100  includes an upper cavity  102  and an opposing lower cavity  104  coupled together in flow communication via a fluid passage  106 . In the exemplary embodiment, the upper cavity  102  has a generally concave cross-sectional shape, defined by a generally concave body portion  108  of the central body  100 . The lower cavity  104  has a generally rectangular cross-sectional shape, defined by a lower wall  110  that extends generally vertically downward from a central portion of the concave body portion  108 . An upper portion of the end of the fluid passage  106  is open at the lowest point of the upper cavity  102 , and an opposite lower portion of the fluid passage  106  is open at a central portion of the lower cavity  104 . The lower portion of the fluid passage  106  expands outward at the lower cavity  104 , forming a generally inverse funnel cross-sectional shape. In other embodiments, the cross-sectional shapes of the upper cavity  102 , the lower cavity  104 , and the fluid passage  106  may be formed in any configuration that enables the central body  100  to function as describe herein. 
     In the exemplary embodiment, the cartridge  14  includes a lower sealing member  112  configured to couple to the central body  100  and close the lower cavity  104 . The lower sealing member is formed by a lower wall  114  that includes a peripheral channel configured to sealingly engage a rim of the lower wall  100  of the central body  100 . Extending axially, into the lower cavity  104 , is an upper seal wall  116 . A lower cap  118  extends over the lower sealing member  112  and is configured to fixedly engage the lower wall  110  of the central body  100 . This facilitates securing the lower sealing member  112  in sealing contact with the central body  100 , thereby closing the lower cavity  104 . 
     The lower cap  118  includes a lower wall  120  having a centrally located opening  122  that enables access to the lower wall  114  of the sealing member  112 . The lower cap  118  includes a vertically-extending wall  124  that extends upward and downward from a peripheral edge of the lower wall  120 . In the exemplary embodiment, an upper portion of the vertically-extending wall  124  engages the lower wall  110  of the central body  100  via a mechanical latching connection, as indicated at  126 . In other embodiments, the vertically-extending wall  124  may engage the lower wall  110  of the central body  100  using any connection technique that enables the lower cap  118  to fixedly engage the lower wall  110 , for example, via an interference fit, an adhesive bond, a weld joint (e.g., spin welding, ultrasonic welding, laser welding, or heat staking), and the like. In the exemplary embodiment, a lower portion of the vertically-extending wall  124  forms a peripheral sealing surface  128  configured to engage a seal member  130 . As illustrated, the seal member  130  includes a channel  132  configured to frictionally engage the upper rim  68  of the central wall  66 , as described herein. 
     In the exemplary embodiment, the cartridge  14  also includes an upper sealing member  134  or membrane configured to couple to the central body  100  and close the upper cavity  102 . The upper sealing member  134  is formed as a generally flat sealing membrane and includes a peripheral ridge member  136  to facilitate sealingly securing the upper sealing member  134  to the central body  100 . An upper cap  138  extends over the upper sealing member  134  and is configured to fixedly engage the central body  100 . This facilitates securing the upper sealing member  134  in sealing contact with the central body  100 , thereby closing the upper cavity  102 . 
     As illustrated in  FIG. 2 , the upper cap  138  includes a vertically-extending wall  140  that has an inward extending flange member  142  configured to couple to the peripheral ridge member  136  of the upper sealing member  134 . In particular, the flange member  142  cooperates with the wall concave body portion  108  of the central body  100  to compress and sealingly secure the upper sealing member  134  therebetween. In the exemplary embodiment, a lower end of the vertically-extending wall  140  is coupled to a coupling flange  144  of the central body  100  via a weld joint, for example, spin welding, ultrasonic welding, laser welding, or heat staking. In other embodiments, the vertically-extending wall  140  may be coupled to a coupling flange  144  using any connection technique that enables the upper cap  138  to fixedly engage the central body  100 , for example, via an adhesive bond and the like. 
     In the exemplary embodiment, the upper cap  138  also includes upper and lower grooves  146  and  148 , respectively, formed in an outer surface of the vertically-extending wall  140 . The upper and lower grooves  146  and  148  are configured to engage the plurality of spaced flexible tabs  52  of the body  18 , and, in particular, the inward extending protrusions  54  at the free end of the flexible tabs  52 , as is described herein. In addition, the upper cap  138  also includes a plurality of latch receiving openings  150  at an upper portion of the vertically-extending wall  140 . The latch receiving openings  150  are configured to couple to the mechanical controller  16  to secure it to the cartridge  14 . 
     With continued reference to  FIG. 2 , in the exemplary embodiment, the mechanical controller  16  includes at least a controller housing  152 , a plunger member  154 , and a bias member  156  located between the controller housing  152  and the plunger member  154  for biasing the plunger member  154  in an axial direction away from the controller housing  152 . In the exemplary embodiment, the bias member  156  is a compression spring. Alternatively, the bias member  156  may be any type of bias or force provider that enables the mechanical controller  16  to function as describe herein. 
     In the exemplary embodiment, the controller housing  152  includes an upper wall  158  having a curved or dome-shaped cross-sectional profile. Extending generally vertically-downward from the upper wall  158  are a plurality of flexible tabs  160  configured for latching engagement with the latch receiving openings  150  of the upper cap  138 . Each flexible tab  160  includes an inward extending protrusion  162  at the free end of the flexible tab  160  to provide a latching connection with a respective receiving opening  150 , as illustrated in  FIG. 2 . In addition, the controller housing  152  includes a bias member guide  164  extending downward coaxially from the upper wall  158  for extending into, and facilitating locating, the bias member  156 . 
     The plunger member  154  includes a guide wall  166  coaxially extending vertically-upward from a domed head  168 . As illustrated, the guide wall is configured to receive the bias member  156  therein, and extend around the bias member guide  164 . The domed head  168  is configured to engage the upper sealing member  134  of the cartridge  14  via force applied by the bias member  156  during use of the fluid delivery apparatus  10 . 
     As described herein with respect to  FIG. 1 , the fluid delivery apparatus  10  includes a microneedle array assembly  80  coupled to the mounting surface  74  located within the mounting space  72  of the microneedle array support structure  42 . While the microneedle array assembly  80  is described herein as being used with the exemplary fluid delivery apparatus  10 , it is contemplated that the microneedle array assembly  80  may be used, or otherwise incorporated into other suitable fluid delivery device. For example, the fluid delivery apparatus  10  may be replaced with other suitable devices for delivering a fluid to an inlet or inlet channel of the microneedle array  80 . 
       FIG. 3  is an exploded schematic of an exemplary microneedle array assembly  80  for use with the fluid delivery apparatus  10  shown in  FIG. 1 .  FIG. 4  is a schematic cross-sectional view of the microneedle array assembly  80  of  FIG. 3 . In the exemplary embodiment, the microneedle array assembly  80  is bonded to the mounting surface  74  via an adhesive layer  176 . The microneedle array assembly  80  includes a microneedle array  170  and a membrane  174  draped at least partially across a plurality of microneedles  178  and a base surface  180  of the microneedle array  170 . The microneedle array assembly  80  also includes a distribution manifold  172  that extends across a back surface  182  of the microneedle array  170  and is bonded thereto by an additional adhesive layer  176 . The distribution manifold  172  includes a fluid distribution network  184  for providing a fluid to the microneedle array  170 . The fluid supplied from the distribution manifold  172  may be in the form of a liquid drug formulation. The membrane-draped microneedles  178  are configured to penetrate a user&#39;s skin, such as for providing the liquid drug formulation into the users skin by way of one or more apertures formed in each microneedle  178 . 
     In the exemplary embodiment, the draped membrane  174  may be fabricated from a polymeric (e.g., plastic) film, or the like, and coupled to the microneedle array  170  using adhesive  176 . In other embodiments, the draped membrane  174  may include an embossed or nano-imprinted, polymeric (e.g., plastic) film, or be fabricated from a polyether ether ketone (PEEK) film that is about five microns thick, or the draped membrane may be any other suitable material, such as a polypropylene film. It is contemplated that the microneedle array assembly  80  may not include the draped membrane  174  in some embodiments. 
     In the exemplary embodiment, the microneedle array  170  may be fabricated from a rigid, semi-rigid, or flexible sheet of material, for example, without limitation, a metal material, a ceramic material, a polymer (e.g., plastic) material, or any other suitable material that enables the microneedle array  170  to function as described herein. For example, in one suitable embodiment, the microneedle array  170  may be formed from silicon by way of reactive-ion etching, or in any other suitable fabrication technique. 
     As shown in  FIG. 4 , the microneedle array  170  includes a plurality of microneedles  178  that extend outwardly from the back surface  182  of the microneedle array  170 . The microneedle array  170  includes a plurality of passageways  208  extending between the back surface  182  for permitting the fluid to flow therethrough. For example, in the exemplary embodiment, each passageway  208  extends through the microneedle array  170  as well as through the microneedle  178 . 
     Each microneedle  178  includes a base that extends downwardly from the back surface  182  and transitions to a piercing or needle-like shape (e.g., a conical or pyramidal shape or a cylindrical shape transitioning to a conical or pyramidal shape) having a tip  210  that is distant from the back surface  182 . The tip  210  of each microneedle  178  is disposed furthest away from the microneedle array  170  and defines the smallest dimension (e.g., diameter or cross-sectional width) of each microneedle  178 . Additionally, each microneedle  178  may generally define any suitable length “L” between the base surface  180  of the microneedle array  170  its tip  210  that is sufficient to allow the microneedles  178  to penetrate the user&#39;s skin. In the exemplary embodiment, each microneedle  178  has a length L of less than about 1000 micrometers (um). Each microneedle  178  may generally have any suitable aspect ratio (i.e., the length L over a cross-sectional width dimension D of each microneedle  178 ). The aspect ratio may be greater than 2, such as greater than 3 or greater than 4. In instances in which the cross-sectional width dimension (e.g., diameter) varies over the length of each microneedle  31 , the aspect ratio may be determined based on the average cross-sectional width dimension. 
     The channels or passageways  208  of each microneedle  178  may be defined through the interior of the microneedles  178  such that each microneedle forms a hollow shaft, or may extend along an outer surface of the microneedles to form a downstream pathway that enables the fluid to flow from the back surface  182  of the microneedle array  170  and through the passageways  208 , at which point the fluid may be delivered onto, into, and/or through the user&#39;s skin. The passageways  208  may be configured to define any suitable cross-sectional shape, for example, without limitation, a semi-circular or circular shape. Alternatively, each passageway  208  may define a non-circular shape, such as a “v” shape or any other suitable cross-sectional shape that enables the microneedles  178  to function as described herein. 
     The microneedle array  170  may generally include any suitable number of microneedles  178  extending from back surface  182 . For example, in some suitable embodiments, the quantity of microneedles  178  included within the microneedle array  170  is in the range between about 10 microneedles per square centimeter (cm 2 ) to about 1,500 microneedles per cm 2 . The microneedles  178  may generally be arranged in a variety of different patterns. For example, in some suitable embodiments, the microneedles  178  are spaced apart in a uniform manner, such as in a rectangular or square grid or in concentric circles. In such embodiments, the spacing of the microneedles  178  may generally depend on numerous factors, including, but not limited to, the length and width of the microneedles  31 , as well as the amount and type of liquid formulation that is intended to be delivered through or along the microneedles  31 . 
       FIG. 5  is a schematic plan view of the distribution manifold  172  for use with the microneedle array  170  of  FIG. 3 .  FIG. 6  is a sectional view of the distribution manifold  172  taken about line A-A, illustrating an exemplary profile of a supply channel  192 . In the exemplary embodiment, the distribution manifold  172  includes the fluid distribution network  184  formed therein. The fluid distribution network includes, for example, a plurality of channels and/or apertures extending between a top surface  186  and a bottom surface  188  of the distribution manifold  172 . The channels and/or apertures include a centrally-located inlet channel  190  coupled in flow communication with a plurality of supply channels  192 , and the fluid passage  86  (shown in  FIG. 1 ) of the microneedle array support structure  42  (shown in  FIG. 1 ). In the exemplary embodiment, the plurality of supply channels  192  include  5  substantially parallel, equispaced channels  192  extending longitudinally along the distribution manifold  172 . In addition, a single supply channel  192  extends transversely across the  5  substantially parallel, equispaced channels  192  at about a midpoint of the channels. The supply channels  192  facilitate distributing a fluid supplied by the inlet channel  190  across an area of the distribution manifold  172 . 
     Each of the  5  substantially parallel, equispaced supply channels  192  are coupled in flow communication to a plurality of resistance channels  194 . The resistance channels  194  extend away from the supply channels  192  and are equispaced along the longitudinal length of the channels. In addition, the resistance channels  194  are formed symmetrically with each other along an axis of the respective supply channel  192 . The resistance channels  194  have a size that is smaller than a size of the supply channels  192 . Moreover, the resistance channels  194  are formed to create a tortuous flow path for the fluid, thereby facilitating an increase of the resistance of the fluid distribution network  184  to the flow of the fluid. Each one of the resistance channels  194  are coupled in flow communication to an outlet channel  196 . As illustrated in  FIG. 4 , each outlet channel  196  is aligned with a respective microneedle  178  for distributing the fluid through the microneedles passageway  208 . In other embodiments, the channels  190 ,  192 ,  194 , and  196  may be formed in any configuration that enables the distribution manifold  172  to function as described herein. 
     In the exemplary embodiment, the supply channel  192  has a generally U-shape having a width “W” and a depth “D.” A D/W ratio of the channel is configured to be in the range of about 0.2 to about 2.2. In some embodiments, corners  198  formed at the bottom of the channels, for example, the supply channel  192 , are rounded to facilitate reducing the formation of bubbles in the fluid as it flows through the channels ( FIG. 6 ). The size and shape of the channels  190 ,  192 ,  194 , and  196 , including the respective corners  198 , is predetermined based on a desired flow rate, pressure drop, and/or fabrication limitations. 
     In the exemplary embodiment, the distribution manifold  172  is formed by bonding a base substrate  200  including the inlet channel  190  formed through the substrate, and the supply channels  192  and the resistance channels  194  formed in a bottom surface  204 , to a cover substrate  202  including the outlet channels  196  formed therethrough. The inlet channel  190  may be formed in the substrate  200  by drilling, cutting, etching, and or any other manufacturing technique for forming a channel or aperture through substrate  200 . In the exemplary embodiment, the supply channels  192  and the resistance channels  194  are formed in the bottom surface  204  of the substrate  200  using an etching technique. For example, in one suitable embodiment, wet etching, or hydrofluoric acid etching, is used to form the supply channels  192  and the resistance channels  194 . A mask is applied to the bottom surface  204  of the substrate  200  to form the location of the channels to an accuracy of less than 2 micrometers, for example. The etching material (e.g., hydrofluoric acid) is applied to the bottom surface  204  to remove material from the bottom surface, thereby forming the supply channels  192  and the resistance channels  194 . In general, wet etching results in a channel that has a D/W ratio of about 0.5 and rounded corners. In another suitable embodiment, Deep Reactive Ion Etching (DRIE or plasma etching) may be used to create deep, high density, and high aspect ratio structures in substrate  200 . DRIE etching enables channels to be created that include steep sidewalls with variable inclination as well as sidewalls with rounded corners. Alternatively, the supply channels  192  and resistance channels  194  can be formed in bottom surface  204  using any fabrication process that enables the distribution manifold  172  to function as described herein. In the exemplary embodiment, the outlet channels  196  are formed through the cover substrate  202  by drilling, cutting, etching, and or any other manufacturing technique for forming a channel or aperture through substrate  202 . 
     In the exemplary embodiment, the base substrate  200  and the cover substrate  202  are bonded together in face-to-face contact to seal the edges of the supply channels  192  and the resistance channels  194  of the distribution manifold  172 . In one suitable embodiment, direct bonding, or direct aligned bonding, is used by creating a prebond between the two substrates  200  and  202 . The prebond can include applying a bonding agent to the bottom surface  204  of the substrate  200  and the top surface  206  of the cover substrate  202  before bringing the two substrates into direct contact. The two substrates  200  and  202  are aligned and brought into face-to-face contact and annealed at an elevated temperature. In another suitable embodiment, anodic bonding is used to form the distribution manifold  172 . For example, an electrical field is applied across the bond interface at surfaces  204  and  206 , while the substrates  200  and  202  are heated. In an alternative embodiment, the two substrates  200  and  202  may be bonded together by using a laser-assisted bonding process, including applying localized heating to the substrates  200  and  202  to bond them together. 
     In the exemplary embodiment, the base substrate  200  and the cover substrate  202  are fabricated from a glass material. Alternatively, the base substrate  200  and the cover substrate  202  may be fabricated from silicon. It is contemplated that the base substrate  200  and the cover substrate  202  may be fabricated from different materials, for example, substrate  200  may be fabricated from a glass and the substrate  202  may fabricated from a silicon. In other embodiment, the base substrate  200  and the cover substrate  202  may be fabricated from any material and material combination that enables the distribution manifold  172  to function as described herein. 
     With reference to  FIGS. 1 and 2 , during operation of the fluid delivery apparatus  10 , the plunger member  154  applies a pressure to the cartridge  14  via the bias member  156  and a fluid contained in the upper cavity  102  flows through the cannula  82  into the fluid passage  86 . The fluid exits the fluid passage  86  by flowing through the inlet channel  190  of the distribution manifold  172 , and then the fluid flows through the supply channels  192 , the resistance channels  194 , and the outlet channel  196  to the passageways  208  of the microneedles  178  and into the user&#39;s skin. 
     In the exemplary embodiment, the bias member  156  functions in connection with the plunger member  154  to provide substantially complete emptying of the fluid from the cartridge  14  through the cannula  82  and into the fluid passage  86 . The plunger member  154  and bias member  156  may provide an initial force in a range of about 32 kilopascals (kPa) (4.6 pounds per square inch (psi)) to about 120 kPa (17.4 psi). The fluid delivery apparatus  10  shown in  FIG. 1  is provided as an example only. That is, the microneedle array assembly  80  may be used with or otherwise incorporated into any other suitable devices. For example, the plunger member  154 , bias member  156 , and/or mechanical controller  16  may be replaced with other suitable features for forcing the fluid into the fluid passage  86 , or the like. 
       FIG. 7  is a representation of a portion of the microneedle array assembly  80  and the resistance to a fluid flow therein. It is assumed that the fluid distribution network  184  of the microneedle array  170  is full of the fluid. The fluid flowing through the distribution manifold  172  enters the inlet channel  190  at a pressure P in  and a flow rate Q in , and is channeled to the supply channel  192 . The flow resistance to the fluid flowing through the supply channel  192  is relatively small and is represented by R 1 , R 2 , and R 3  as the fluid flows along the supply channel  192 . However, as the fluid enters the resistance channels  194 , the resistance to flow is substantially increased, which is represented by R 4 , R 5 , and R 6 , respectively. For example in one suitable embodiment, the resistance to flow through the resistance channels  194  (represented by resistance values R 4 , R 5 , and R 6 ) is at least about 5 times greater than the resistance to flow through the supply channels  192 . In some embodiments, the resistance to flow through the resistance channels  194  at least about 30 times greater than, at least about 50 times greater than, between about 5 and about 100 times greater than, between about 40 and about 100 times greater than, or between about 50 and about 100 times greater than the resistance to flow through the supply channels  192 . The resistance values R 4 , R 5 , and R 6  of the resistance channels  194  are significantly higher than the respective resistance values R 1 , R 2 , and R 3  due, in part, by the resistance channels  194  being fabricated with a much smaller cross-sectional area than the cross-sectional area of the supply channels  192 . The increased resistance values R 4 , R 5 , and R 6  result in a pressure drop across the resistance channels  194  (for example, P 4 -P 1 , P 5 −P 2 , and P 6 −P 3 ) such that fluid pressures P 1 , P 2 , and P 3  along the supply channel  192  are substantially equal. Thus, because P 1 , P 2 , and P 3  are substantially equal, the resistance channels  194  can be fabricated essentially the same size to provide substantially the same resistance values R 4 , R 5 , and R 6 . Flow resistance through each of the microneedles  178  of the microneedle array  170  is substantially the same and is represented by R 7 , R 8 , and R 9 , respectively. Thus, substantially equal pressure drops across the microneedles  178  (for example, P 7 −P 4 , P 8 −P 5 , and P 9 −P 6 ) result in flow rates Q 1 , Q 2 , and Q 3  at respective microneedles  178  being substantially the same. In the exemplary embodiment, the flow rate through each microneedle  178  is in the range between about 0.1 microliter per hour (uL/hr) to about 20.0 uL/hr. In some suitable embodiments, the flow rate through each microneedle  178  is in the range between about 0.25 uL/hr to about 5.0 uL/hr, and preferably, about 1 uL/hr. 
     Thus, in the exemplary embodiment, by substantially increasing the resistance value across the resistance channels  194 , the theoretical difference in pressures, e.g., P 1 , P 2 , and P 3  due to the resistance values R 1 , R 2 , and R 3  is essentially eliminated. Thus, a flow rate exiting any respective microneedle  178  is substantially the same, thereby facilitating a substantially equal distribution of the fluid across the entirety of the microneedle array  170 . 
     In the exemplary embodiment, the pressures P 7 , P 8 , and P 9  at the downstream openings of the microneedles  178  are in the range between about 2 kPa (0.29 psi) to about 50 kPa (7.25 psi) and, in one suitable embodiment, are desired to be about 20 kPa (2.9 psi) to ensure sufficient pressure to distribute the fluid into a user&#39;s skin. In general, the pressure drop across a microneedle  178  is small such that the pressure on either side of a microneedle  178  is nearly the same. This enables the microneedle array assembly  80  to be substantially insensitive to resistance variability of the microneedles  178  because the resistance across the microneedles  178  is much smaller than the resistance across the distribution manifold  172 . For example, in the exemplary embodiment, the pressure drop across the distribution manifold  172  is at least about 20 kPa (2.9 psi), which enables the pressure in the supply channels  192  to be substantially the same. Thus, a pressure in the supply channels  192  is in the range between about 32 kPa (4.6 psi) to about 80 kPa (11.6 psi), and, in one suitable embodiment, is desired to be at least about 50 kPa (7.25 psi) to ensure an outlet pressure of 20 kPa (2.9 psi) at the exit of the microneedle array  170 . 
     In the exemplary embodiment, the bias member  156  is configured to maintain a generally continuous outlet pressure at or above about 20 kPa (2.9 psi) for at least about 90% of the fluid volume in the cavity  102  (shown in  FIG. 2 ). For example, in one embodiment, the bias member  156  is configured to be a continuous or constant pressure device, for example a constant force coil spring that over a distance of travel of the plunger member  154  (shown in  FIG. 2 ), the force is generally constant, or a change in the force is substantially small. In general, a typical coil spring will have a variable rate, i.e., the resistance of the spring to load varies during compression/extension. Thus, in the exemplary embodiment, if a typical variable rate bias member is used, as the bias member extends to force the fluid out of the upper cavity  102 , the force exerted on the fluid would tend to decrease. This could result in an outlet pressure at the exit of the microneedle array  170  falling below the 20 kPa (2.9 psi) pressure desired to ensure the fluid is distributed the fluid into a user&#39;s skin. In another embodiment, the bias member  156  includes two parallel springs. For example, the bias member  156  may include a low force spring that has a first length, and a high force spring that has a second length that is shorter than the first length of the low force spring. Such a configuration enables the bias member  156  to have a pressure profile that is high pressure for a first period, and then a reduced pressure for a second period. 
     In addition to maintaining a generally constant outlet pressure, it is desired to have an increased initial pressure P in  to facilitate a generally continuous fill rate of the fluid into the user&#39;s skin. If the bias member  156  is not a generally constant pressure device, or if the initial pressure exerted by the bias member is relatively low, the flow rate of the fluid into the user&#39;s skin can vary substantially with time. For example, a low initial pressure of a decaying amount of pressure can result in the initial increasing fill rate of the fluid into the user&#39;s skin slowing and/or stopping for a period of time. Many medicines benefit from having a steady state concentration in the patient&#39;s blood stream, thus it is desirable to maintain a generally continuous fill rate. It has be found that increasing the initial pressure of the bias member, while still maintaining the desired outlet pressure of 20 kPa (2.9 psi) at the exit of the microneedle array  170  facilitates maintaining a generally continuous and generally steady fill rate. 
       FIG. 8  is an exploded schematic of another exemplary microneedle array assembly  220  for use with the fluid delivery apparatus  10  shown in  FIG. 1 . While the microneedle array assembly  220  is described herein as being used with the exemplary fluid delivery apparatus  10 , it is contemplated that the microneedle array assembly  220  may be used, or otherwise incorporated into other suitable fluid delivery device. For example, the fluid delivery apparatus  10  may be replaced with other suitable devices for delivering a fluid to an inlet or inlet channel of the microneedle array  220 .  FIG. 9  is a schematic cross-sectional view of the microneedle array assembly  220  of  FIG. 8 . In the exemplary embodiment, the microneedle array assembly  220  is bonded to the mounting surface  74  via an adhesive layer  222 . The microneedle array assembly  220  includes a microneedle array  224  and a membrane  226  draped at least partially across a plurality of microneedles  228  and a base surface  230  of the microneedle array  224 . The microneedle array assembly  220  also includes a distribution manifold  232  that extends across a back surface  234  of the microneedle array  224  and is bonded thereto. The distribution manifold  232  includes a fluid distribution network  236  for providing a fluid to the microneedle array  224 . The fluid supplied from the distribution manifold  232  may be in the form of a liquid drug formulation. The membrane-draped microneedles  228  are configured to penetrate a user&#39;s skin, such as for providing the liquid drug formulation into the user&#39;s skin by way of one or more apertures  238  formed in each microneedle  228 . 
     In the exemplary embodiment, the draped membrane  226  is formed substantially identically to the draped membrane  174  described herein with respect to  FIGS. 3 and 4 . As with draped membrane  174 , it is contemplated that microneedle array assembly  220  may be free of draped membrane  226  in some suitable embodiments. 
     In the exemplary embodiment, the microneedle array  224  may be fabricated from a rigid, semi-rigid, or flexible sheet of material, for example, without limitation, a metal material, a ceramic material, a polymer (e.g., plastic) material, or any other suitable material that enables the microneedle array  224  to function as described herein. For example, in one suitable embodiment, the microneedle array  224  may be formed from silicon by way of reactive-ion etching, or in any other suitable fabrication technique. 
       FIG. 10  is a schematic plan view of the back surface  234  of the microneedle array  224  for use with the microneedle array assembly  220  of  FIG. 8 , including the distribution manifold  232 . In the exemplary embodiment, the distribution manifold  232  includes the fluid distribution network  236  formed therein. The fluid distribution network includes, for example, a plurality of channels and/or apertures extending between a top surface  240  and a bottom surface  242  of the distribution manifold  232 . The channels and/or apertures include a centrally-located inlet channel  244  coupled in flow communication with a supply channel  246  and the fluid passage  86  (shown in  FIG. 1 ) of the microneedle array support structure  42  (Shown in  FIG. 1 ). In the exemplary embodiment, the supply channel  246  extends longitudinally along the distribution manifold  232 . The supply channel  246  facilitates distributing a fluid supplied by the inlet channel  244  across an area of the distribution manifold  232 . 
     The supply channel  246  is coupled in flow communication to a plurality of supply troughs  248  formed in the back surface  234  of the microneedle array  224 . The supply troughs  248  extend away from the supply channel  246  and are formed to create a resistance to a fluid flow that enables each of the supply troughs  248  to have a substantially identical fluid outlet pressure. For example, in one embodiment, the supply channels  246  form a tortuous flow path for the fluid, thereby facilitating an increase of the resistance of the supply troughs  248  to the flow of the fluid via a length of the channels. Each one of the supply troughs  248  are coupled in flow communication to the apertures  238  formed in each microneedle  228 , as illustrated in  FIG. 9 . In other embodiments, the channels  246  and  248  may be formed in any configuration that enables the distribution manifold  232  to function as described herein. In the exemplary embodiment, the supply channel  246  and the supply troughs  248  have a generally rectangular shape substantially as described herein with respect to the supply channel  192  described in  FIG. 6 . 
     The inlet channel  244  may be formed in the distribution manifold  232  by drilling, cutting, etching, and or any other manufacturing technique for forming a channel or aperture through the distribution manifold. In the exemplary embodiment, the supply channel  246  is formed in the bottom surface  242  of the distribution manifold  232  using an etching technique. For example, in one suitable embodiment, wet etching, or hydrofluoric acid etching, is used to form the supply channel  246 . For example, a mask is applied to the bottom surface  242  of the distribution manifold  232  to form the location of the channel to an accuracy of less than 2 micrometers, for example. As described herein, an etching material (e.g., hydrofluoric acid) is applied to the bottom surface  242  to remove material from the bottom surface, thereby forming the supply channel  246 . In another suitable embodiment, DRIE or plasma etching may be used to create the supply channel  246 . Alternatively, the supply channel  246  can be formed in bottom surface  242  using any fabrication process that enables the distribution manifold  232  to function as described herein. In the exemplary embodiment, the supply troughs are formed in the back surface  234  of the microneedle array  224  using the same etching techniques described with respect to the supply channel  246 . 
     In the exemplary embodiment, the distribution manifold  232  and the microneedle array  224  are bonded together in face-to-face contact to seal the edges of and close the supply channel  246  and the supply troughs  248 . In one suitable embodiment, direct bonding, or direct aligned bonding, is used by creating a prebond between the distribution manifold  232  and the microneedle array  224 , as is described herein. In another suitable embodiment, anodic bonding is used to bond the distribution manifold  232  to the microneedle array  224 . In an alternative embodiment, the distribution manifold  232  and the microneedle array  224  may be bonded together by using a laser-assisted bonding process, including applying localized heating to the distribution manifold  232  and the microneedle array  224  to bond them together. 
     In the exemplary embodiment, the distribution manifold  232  is fabricated from a glass material. Alternatively, the distribution manifold  232  may be fabricated from silicon. The microneedle array  224  is fabricated from silicon. However, in other embodiments, the microneedle array  224  may be fabricated from a glass material. It is contemplated that the distribution manifold  232  and the microneedle array  224  may be fabricated from any material and material combination that enables the microneedle array assembly  220  to function as described herein. 
     In this embodiment, the fluid enters the supply channel  246  via the inlet channel  244  and flows along and fills the supply channel  246  to distribute the fluid to the supply troughs  248  formed on the back surface  234  of the microneedle array  224 . Each respective supply trough  248  for each individual microneedle  228  is different in length such that the flow rate from the inlet channel  244  of the distribution manifold  232  to the passageway  238  of the microneedle  228  is the same for all microneedles  228 . 
       FIG. 11  is an exploded schematic of another exemplary microneedle array assembly  250  for use with the fluid delivery apparatus  10  shown in  FIG. 1 . While the microneedle array assembly  250  is described herein as being used with the exemplary fluid delivery apparatus  10 , it is contemplated that the microneedle array assembly  250  may be used, or otherwise incorporated into other suitable fluid delivery devices. For example, the fluid delivery apparatus  10  may be replaced with other suitable devices for delivering a fluid to an inlet or inlet channel of the microneedle array  250 ,  FIG. 12  is a schematic cross-sectional view of the microneedle array assembly  250  of  FIG. 11 . In the exemplary embodiment, the microneedle array assembly  250  is bonded to the mounting surface  74  (shown in  FIG. 1 ) via an adhesive layer  252 . The microneedle array assembly  250  includes a microneedle array  254  of substantially the same construction of the microneedle array  170  described herein in relation to  FIGS. 3 and 4 , and a membrane  256  draped at least partially across a plurality of microneedles  258  and a base surface  260  of the microneedle array  254 . The microneedle array assembly  250  also includes a distribution manifold  262  that extends across a back surface  264  of the microneedle array  254  and is bonded thereto. The distribution manifold  262  includes a fluid distribution network  266 , including a plurality of channels  274  and/or apertures  272  and  276 , for providing a fluid to the microneedle array  254 . The membrane-draped microneedles  258  are configured to penetrate a user&#39;s skin, such as for providing the fluid into the user&#39;s skin by way of one or more apertures  268  formed in each microneedle  258 . 
     In the exemplary embodiment, the draped membrane  256  is formed substantially identically to the draped membrane  174  described herein with respect to  FIGS. 3 and 4 . As with draped membrane  174 , it is contemplated that microneedle array assembly  250  may be free of draped membrane  256  in some suitable embodiments. 
     In the exemplary embodiment, the microneedle array  254  may be fabricated from a rigid, semi-rigid, or flexible sheet of material, for example, without limitation, a metal material, a ceramic material, a polymer (e.g., plastic) material, or any other suitable material that enables the microneedle array  254  to function as described herein. For example, in one suitable embodiment, the microneedle array  254  is fabricated from silicon by way of reactive-ion etching, or in any other suitable fabrication technique. 
       FIG. 13  is a schematic plan view of a back surface  264  of the distribution manifold  262  for use with the microneedle array assembly  250  of  FIG. 11 . In the exemplary embodiment, the distribution manifold  262  includes the fluid distribution network  266  formed therein. The fluid distribution network includes, for example, a plurality of channels and/or apertures extending between a top surface  270  and the back surface  264  of the distribution manifold  262 . The channels and/or apertures include a centrally-located inlet channel  272  coupled in flow communication with a plurality of supply channels  274  and the fluid passage  86  (shown in  FIG. 1 ) of the microneedle array support structure  42  (shown in  FIG. 1 ). In the exemplary embodiment, the supply channels  274  extend along the distribution manifold  262 , forming a tortuous path for the fluid, thereby facilitating an increase of the resistance of the supply channels  274 . The supply channels  274  facilitate distributing a fluid supplied by the inlet channel  272  across an area of the distribution manifold  262 . 
     Each of the supply channels  274  is coupled in flow communication to an outlet channel  276 . Each outlet channel  276  is generally aligned with a respective microneedle  258  for distributing the fluid through the passageways  268  of the microneedles  258 , as illustrated in  FIG. 12 . In other embodiments, the supply channels  274  and the outlet channels  276  may be formed in any configuration that enables the distribution manifold  262  to function as described herein. In the exemplary embodiment, the supply channels  274  have a generally rectangular shape substantially as described herein with respect to the supply channel  192  described in  FIG. 6 . 
     The inlet channel  272  may be formed in the distribution manifold  262  by drilling, cutting, etching, and or any other manufacturing technique for forming a channel or aperture through the distribution manifold. In the exemplary embodiment, the supply channels  274  are formed on the bottom surface  268  of the distribution manifold  262  by molding the set of channels  274  into the distribution manifold  262 . Alternatively, the supply channels  274  can be formed on bottom surface  268  using any fabrication process that enables the distribution manifold  262  to function as described herein. 
     In the exemplary embodiment, the distribution manifold  262  and the microneedle array  254  are bonded together in face-to-face contact to seal the edges of and close the supply channels  274 . In one suitable embodiment, direct bonding, or direct aligned bonding, is used by creating a prebond between the distribution manifold  262  and the microneedle array  254 , as is described herein. In another suitable embodiment, anodic bonding is used to bond the distribution manifold  262  to the microneedle array  254 . In an alternative embodiment, the distribution manifold  262  and the microneedle array  254  may be bonded together by using a laser-assisted bonding process, including applying localized heating to the distribution manifold  262  and the microneedle array  254  to bond them together. 
     In the exemplary embodiment, the distribution manifold  262  is fabricated from a polydimethylsiloxane (PDMS) polymer. Alternatively, the distribution manifold  232  may be fabricated from any material and material combination that enables the microneedle array assembly  250  to function as described herein. 
     In this embodiment, the fluid enters the supply channels  274  via the inlet channel  272  and flows along and fills the supply channels  274  to distribute the fluid to each individual microneedle  258 . Each supply channel  274  is substantially the same length such that the total flow resistance from the inlet channel  272  of the distribution manifold  262  to the passageway  268  of the microneedle  258  is the same for all microneedles  258 . Thus, because a resistance to each microneedle  258  is substantially the same, the flow rate is also substantially the same to all microneedles  258 . The path of the individual supply channels  274  is determined based on the location of the respective microneedle  258  that the channel is connected to. 
     The apparatus, system, and methods described in detail herein enable a microneedle array assembly to distribute a substantially equal quantity of a medicine through each microneedle of the microneedle assembly. A microfluidic distribution manifold for use with a microneedle assembly includes fluid supply channel features that enable a total flow resistance in each supply channel to be substantially equal, thereby generating an equalized flow rate. In addition, the resistance levels of the flow channels can be configured to enable a substantially constant flow rate of the fluid over an extended period of time, thereby facilitating a steady state concentration of the fluid in the user&#39;s blood stream. 
     Exemplary embodiments of an apparatus, system, and methods for a microfluidic distribution manifold are described above in detail. The apparatus, system, and methods described herein are not limited to the specific embodiments described, but rather, components of apparatus, systems, and/or steps of the methods may be utilized independently and separately from other components and/or steps described herein. For example, the methods may also be used in combination with other fluid delivery apparatus, systems, and methods, and are not limited to practice with only the apparatuses, systems, and methods described herein. Rather, the exemplary embodiments can be implemented and utilized in connection with many fluid delivery applications. 
     Although specific features of various embodiments of the disclosure may be shown in some drawings and not in others, this is for convenience only. In accordance with the principles of the disclosure, any feature of a drawing may be referenced and/or claimed in combination with any feature of any other drawing. 
     This written description uses examples to disclose the embodiments, including the best mode, and also to enable any person skilled in the art to practice the embodiments, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the disclosure is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims. 
     As various changes could be made in the above embodiments without departing from the scope of the disclosure, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.