Patent Publication Number: US-2021178137-A1

Title: Microarray applicator

Description:
BACKGROUND 
     Microneedle applicators having complex actuation systems, such as those using springs or other stored energy devices to cause the microneedles to come into contact with the skin, are known. Such applicators are expensive to manufacture so they are designed to be used multiple times. They also have complex components, so they are expensive to replace or repair. 
     SUMMARY 
     A microarray applicator can include a housing, the housing having a first major surface configured to positioned towards skin and defining the bottom of the housing, a second major surface opposite the first major surface and defining the top of the housing, a cavity extending through the first and second major surfaces, and an interior surface defining the cavity. The interior surface can have one or more ridges, each having a ridge width, as well as a ridge height defined by the distance between the ridge and the first major surface, and a holder located between the first and second major surfaces for holding at least part of a microarray device within the housing. 
     The microarray applicator can further include a plunger. The plunger has a top, a bottom, and one or more sides. A first set of one or more notches is located proximate to the bottom of the plunger, each of the one or more notches in the first set of one or more notches being located substantially the same distance from the bottom of the plunger, and having a first depth into one or more sides, such that when the first notch is fully engaged with the ridge in the housing a first force can release the first notch in a direction towards the bottom of the housing and a second force can release the first notch in a direction towards the top of the housing, the first force being substantially the same as the second force. The plunger also has a second set of one or more notches located proximate to the top of the plunger, each of the one or more notches in the second set of one or more notches being located substantially the same distance from the top of the plunger, and extending a second depth into the one or more sides in such that when the second notch is fully engaged with the ridge in the housing a third force can release the second notch in a direction towards the bottom of the housing and a fourth force can release the second notch in a direction towards the top of the housing, the third force being substantially the same as the fourth force. 
     The second depth is equal to or greater than the first depth, and equal to or less than the ridge width. The distance between the first set of one or more notches and the second set of one or more notches is greater than the notch height. The plunger is slidably engageable with the cavity in the housing to be moveable between a first position wherein the first set of one or more notches is engaged with the one or more ridges in the housing and the bottom of the plunger does not extend below the first major surface of the housing, and a second position wherein the second set of one or more notches is engaged with the one or more ridges in the housing and the bottom of the plunger extends below the first major surface of the housing. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a top-down view of a housing; 
         FIG. 2A  is a cut-away side view of a housing; 
         FIG. 2B  is a detailed view of a portion of the housing shown in  FIG. 2A ; 
         FIG. 3  is a cut-away side view of a housing; 
         FIG. 4  is a bottom view of a housing; 
         FIG. 5  is a three-quarter profile view of a housing; 
         FIG. 6  is a three-quarter view of a plunger; 
         FIG. 7A  is a side view of a plunger; 
         FIGS. 7B and 7C  are detailed view of portions of the plunger of  7 A, shown from a cut-away side view; 
         FIG. 8A  is a three-quarter bottom view of a microarray carrier with a patch; 
         FIG. 8B  is a three-quarter bottom view of a microarray carrier without a patch; 
         FIG. 9A  is a cut-away side view of an assembled plunger and housing in a first position; 
         FIG. 9B  is a detailed view of a portion of  FIG. 9A ; 
         FIG. 9C  is a cut-away side view of an assembled plunger and housing in a second position; 
         FIG. 10A  is a cut-away side view of an assembled plunger, housing, and microarray carrier; and 
         FIG. 10B  is a cut-away side view of an assembled plunger, housing, and microarray carrier being applied to a skin surface. 
     
    
    
     DETAILED DESCRIPTION 
     Throughout this disclosure, singular forms such as “a,” “an,” and “the” are often used for convenience; however, it should be understood that the singular forms are meant to include the plural unless the singular alone is explicitly specified or is clearly indicated by the context. 
     Positional terms such as “top” and “bottom” or “left” and “right” are not used herein in reference to position with respect to the ground, the user, the floor, the earth, or the direction of a gravitational pull. Instead, these terms are used as relative terms to refer to opposing or approximately opposing sides or portions of an object. For example, while the “top” of an object is understood to be opposing or approximately opposing the “bottom,” it is not necessary that the “bottom” be disposed closer to the ground that the “top.” 
     A microneedle array applicator can include a housing and a plunger. The housing and the plunger can be made of any suitable material, but are most typically plastic. Common plastics that can be used include polyethylene, such as high density polyethylene, polypropylene, nylon, such as nylon 6,6, and the like. The housing and the plunger need not be made of the same material, although this is most common. 
     The housing can have a first major surface that is configured to be positioned towards the skin and defining a bottom of the housing. The first major surface is configured to releaseably engage with a microneedle device, particularly a microarray carrier portion of a microarray applicator. 
     The housing can also have a second major surface opposite the first major surface and defining a top of the housing. 
     The housing can have a cavity that extends through the first and second major surfaces. An interior surface can define the cavity. The interior surface can have one or more ridges. The one or more ridges typically have a ridge height, which is defined by the distance between the one or more ridges and the first major surface. In most cases, the cavity will have an annular shape, not including the one or more ridges, and there will be only one ridge that forms a circle around the entire interior surface. The entire ridge in this case has the same ridge height. In the cases where the cavity has another shape, for example when the cavity has a square, triangular, or other cross-section, then there will be more than one ridge, one ridge per side of the cavity, and each of the ridges will have the same ridge height. 
     The housing can also include a holder located between the first and second major surfaces for holding at least part of a microarray device within the housing. The holder can have any suitable configuration, which will depend in part on the configuration of the microarray device that it is designed to hold. Some exemplary configurations are depicted in U.S. Patent Application Publication No. US2016/0235958, particularly in FIGS. 8, 9, 10, 11, 12, 13, 14, and 15, and in PCT Publication No. WO02/30300, particularly in FIG. 16. One particular configuration for the holder is shown in the Figures of this disclosure, although it should be understood that other configurations are possible. In the configuration depicted in the Figures of this disclosure, the holder is in the form of a slot in the housing, the bottom of the slot being defined by the first major surface, and the top of the slot being defined by an additional surface. The microneedle array device can fit within the slot and slideably engage with the holder. Groves can be present in the slot to engage with the microneedle array device. 
     In many cases, depending on the configuration of the holder, the first major surface does not extend all the way across the housing. In such cases, the first major surface can, for example, extend only part of the way across the housing, extend only along parts of one or more sides or edges of the housing, and the like. Nonetheless, even in cases where the first major surface is part of the holder, the first major surface will typically be below the portion of the housing that is configured to receive the microneedle array device. 
     The plunger can have a top and a bottom, as well as one or more sides. The plunger is configured to slideably engage with the cavity in the housing. In particular, the bottom of the plunger can be placed within the cavity in the housing. Thus, the shape of the plunger will depend on the shape of the cavity of the housing. In most cases the interior cavity of the housing has a circular cross-section, and thus the plunger also has a circular cross-section, and is cylindrical in shape, excluding the ridges. 
     The plunger can have a first set of one or more notches located proximate to the bottom of the plunger, all of which are located substantially the same distance from the top of the plunger. The first set of one or more notches have a first depth into the one or more sides of the plunger. The first width is equal to or less than the ridge width. The first set of one or more notches is configured such that, when fully engaged with the ridge in the housing, a first force can release the first notch in a direction towards the bottom of the housing and a second force can release the first notch in a direction towards the top of the housing, the first force being substantially the same as the second force. The first and the second forces are substantially the same, such that they preferably differ by no more than 10%. This is typically accomplished by providing a first and second notch with a profile that is substantially rotationally symmetric about an axis substantially normal to the side of the plunger adjacent to the notch. “Substantially rotationally symmetric” refers to rotational symmetry that is within manufacturing tolerances, particularly to a rotational symmetry that is greater than 90% symmetrical, and even more particularly to rotational symmetry that is greater than 95%. “Substantially normal,” it is meant that the angle between axis and the side of the plunger is approximately 90°, and in particular cases the angle is from 80° to 100°. 
     The plunger can also have a second set of one or more notches located proximate to the top of the plunger. The second set of one or more notches is configured such that, when fully engaged with the notch in the housing, a third force can release the ridge in a direction towards the bottom of the housing and a fourth force can release the ridge in a direction towards the top of the housing, the third force being substantially the same as the fourth force. The third and fourth forces are substantially the same, and particularly differ by no more than 10%. This is typically accomplished by providing a second notch with a profile that is substantially rotationally symmetric about an axis substantially normal to the side of the plunger adjacent to the ridge. “Substantially rotationally symmetric” refers to rotational symmetry that is within manufacturing tolerances, particularly to a rotational symmetry that is greater than 90% symmetrical, and even more particularly to rotational symmetry that is greater than 95%. “Substantially normal,” it is meant that the angle between axis and the plunger is approximately 90°, and in particular the angle is from 80° to 100°. The second width is equal to or less than the ridge width. 
     The first and second set of one or more notches are separated by a distance. The distance between the first and second sets of one or more notches is greater than the ridge height. 
     The shape of the plunger can vary depending on the shape of the cavity in the housing such that the plunger can slideably engage with the cavity. Typically, when the cavity has a circular cross-section, the plunger also has a circular cross-section. In this case the plunger can be cylindrical. When the plunger is referred to as being cylindrical, this does not include the first and second sets of one or more notches or the optional head (discussed below), which can extend from the plunger making the overall plunger not a perfect cylinder. When the plunger is cylindrical, there is typically only one notch in the first set of one or more notches and only one ridge in the second set of one or more notches. 
     The plunger can slideably engage with the cavity in the housing. The plunger is moveable within the cavity between a first position and a second position within the cavity. In the first position, the first set of one or more notches is engaged with the one or more ridges in the interior of the cavity of the housing, for example, to releasably interlock the plunger with the housing. In the first position, the bottom of the plunger does not extend below the first major surface of the housing. 
     In the second position, the second set of one or more notches engages with the one or more ridges on the interior surface of the cavity, for example to releasably interlock the plunger with the housing. In this position, the bottom of the plunger extends below the first major surface of the housing. The bottom of the plunger extends far enough below the first major surface of the housing that it is capable of ejecting a microneedle patch from a microarray device, when a microarray device, such as a microarray device as described herein, is in the holder of the housing. 
     The top of the plunger can, in some cases, comprise a head. When present, the head typically extends beyond the sides of the plunger farther than the cavity in the housing. Thus, the head can serve to block the top of the plunger from entering the housing. The head can be configured in any suitable shape, but most commonly has a mushroom-cap shape. The head of the plunger, if present, can also make it easier for a user to push the plunger into the housing and from the first position to the second position by providing an increased surface area on which to push. The head of the plunger can also prevent the plunger from moving through the bottom of the housing by abutting the second major surface of the housing when the plunger is in the second position. The head of the plunger is not required, and in some cases it is not present. 
     Typically, the applicator does not include an energy storage device, such as a spring, for moving the plunger from the first position to the second position or from the second position back to the first position. Instead, the force of a user pushing on the top of the plunger, such as the head of the plunger when present, can move the plunger from the first position to the second position. 
     A microarray device can engage with the holder of the housing such that at least a portion of the microarray device is releaseably restrained within the housing. The microarray device will typically have a microarray carrier, which is typically plastic but can be any suitable material including metal or others, that carries a microneedle patch. The microneedle patch is typically in the form of a flexible sheet with microneedles protruding therefrom. The term “microneedles” refers to needles or similar projections having a size on the microscale; other disclosures have used the term “microprotrusions” in the same sense, in which case the term microneedles is intended to include such microprotrusions. Microneedles can be hollow or solid, and can even be dissolvable within the body. When hollow, the microneedles will often contain one or more active agents, often along with optional excipients, within the microneedles. When solid, the microneedles will often contain a coating of one or more active agents, often along with optional excipients. When dissolvable, the microneedles will often be made out of a dissolvable matrix having one or more active agents, often along with optional excipients, in the matrix. The microneedle patch is supported by the microneedle array carrier, but it can be ejected from the carrier in use. 
     In use, the bottom of the plunger can be inserted into the cavity. Pushing on the top of the plunger can move the plunger to the first position wherein the first set of one or more notches is engaged with the ridge in the interior of the cavity. A microneedle device can be placed within the holder (either before or after inserting the plunger into the first position). The second first major surface of the actuator can be placed against the object that is to receive the microneedles, which is usually skin, such as the skin of a subject, but can also be other things such as testing device (e.g., for testing the velocity of the plunger or pressure applied by the plunger), an eye, and the like. The plunger can be inserted and moved to the first position either before or after the second major surface is placed against the skin. 
     A force sufficient to move the plunger from the first position to the second position is applied to the top of the plunger. Typically, this force is sufficient to eject the microneedle patch from the microneedle device, such as to detach the microneedle patch from the microarray carrier, and also sufficient such that the microneedles can pierce the skin of a subject. The required force will vary depending on the particular application, but it can be controlled by varying the depth of the notch and the width of the ridge, as well as the dimensions of the ridge and notch. When the first depth of the first set of one or more notches, and the corresponding depth of the ridge, is larger, then more force is required to disengage the first set of one or more notches from the ridge and move the plunger to the second position increases. When the first depth of the first set of one or more notches, and the corresponding width of the ridge, is smaller, then less force is required to disengage the first set of one or more notches from the ridge and move the plunger to the second position. An increased force requirement to move the plunger from the first to the second position can provide a greater velocity of the plunger, which in turn increases the force applied by the microneedles on the skin. Thus, the velocity, for example, of the plunger and the microneedles when the microneedle patch ejects from the applicator and contacts the skin, can be controlled by varying the first width. 
     Once the plunger has moved to the second position, that is, the second set of notches is engaged with the ridge, continued downward pressure on the plunger provides a pressure on the microneedle patch. The pressure provided can be controlled by way of increasing or decreasing the second width of the second set of one or more ridges. 
     After ejecting the microneedle patch, the plunger can be re-set for another use. To reset the plunger the remaining portion of the microneedle device (that is, the portion that was not ejected) can be removed from the holder in the housing. The bottom of the plunger can then be pushed back up towards the top of the housing until the plunger returns to the first position. A new microneedle device can be placed in the holder, and the microneedle applicator can be used again. However, because the microneedle applicator is a simple design that is inexpensive to manufacture and requires no expensive materials, the microneedle applicator can be designed for a single-use only, and can be discarded after use. 
     Typically, no stored energy devices are used during the process. For example, in most cases no springs or chemical systems are needed to move the plunger between the first and second positions. In the case where a stored energy device is used, it is typically not an integrated component of the actuator. Instead, it is usually a separate device that is used to help push the plunger, for example, in cases where the user does not have sufficient strength to push the plunger hard enough to move it from the first to the second position. In most cases, no stored energy device of any type is used. 
     In some cases, when sufficient force is applied to the plunger, the second set of notches can disengage with the ridge and the plunger can move downwards past the second position. When this is a concern, the head of the plunger can be useful. For example, the head of the plunger, which typically extends beyond the sides of the plunger and the cavity of the housing, can stop the plunger from proceeding too far into the housing, for example, it can stop the top of the plunger from entering the housing. 
     Turning now to the figures,  FIG. 1  is a top-down view of housing  1000  wherein second major surface  1100  and cavity  1200  are visible. In this Figure, cavity  1200  has a circular cross-section. Other shapes are also possible. 
       FIG. 2A  is a cut-away side view of housing  2000 , featuring first major surface  2100  and opposing second major surface  2200 . Cavity  2300  extends through the entire housing  2000 , including featuring first major surface  2100  and second major surface  2200 . Note that in this Figure, first major surface  2100  does not extend all the way across housing  2000 . Holder  2400  is, in this Figure, present in the form of groves in housing  2000  for receiving and retaining a microneedle array device (not shown). Cavity  2300  features interior surface  2310  and notch  2320 . Notch  2320  is characterized notch height  2322 , which is the distance between the notch and first major surface  2100 . 
       FIG. 2B  is a blow-up of a portion of  FIG. 2 , wherein notch  2320  is featured in more detail. Notch depth  2321 , the depth that notch  2320  extends into interior surface  2310 , is visible in this Figure. 
       FIG. 3  is a cut-away side view of housing  3000 , featuring first major surface  3100 , second major surface  3200  and cavity  3300  extending through the entire housing  3000  including featuring first major surface  3100  and second major surface  3200 . In this Figure, first major surface  3100  extends further across housing  3000  than the corresponding first major surface  2100  in  FIG. 2 . Holder  3400  is, in this Figure, present in the form of groves in housing  3000  for receiving and retaining a microneedle array device (not shown). Cavity  3300  features interior surface  3310  and notch  3320 . 
       FIG. 4  is a bottom view of housing  4000 , featuring first major surface  4100 , second major surface  4200 , and cavity  4300 . A holder (not shown) can be present in the form of slots for holding the microneedle array device within the housing. 
       FIG. 5  is a three-quarter view of housing  5000 , wherein the first major surface is not visible, but second major surface  5200  and cavity  5300  are visible. A portion of notch  5320  is visible within cavity  5300 . A portion of holder  5400  for holding a microneedle array device within housing  5000  is also visible. 
       FIG. 6  is a side view of plunger  6000 , featuring top  6100 , bottom  6200  and side  6300 . In  FIG. 6  the plunger  6000  is approximately cylindrical, so there is only one side  6300 , but if the plunger were shaped differently it could have more than one side. On the side  6300  is a first ridge  6310  located proximate to the bottom  6200  of the plunger  6000  and a second ridge  6320  located proximate to the top  6100  of the plunger  6000 . In  FIG. 6 , first ridge  6310  and second ridge  6320  are continuous around the entire side  6300  of plunger  6000 , however other configurations are possible. For example, first ridge  6310  could be first set of multiple ridges the same distance from bottom  6200 . Likewise, second ridge  6320  could be a second set of multiple ridges the same distance from top  6100 . 
       FIG. 7 a    is a side view of plunger  7000 , featuring a top that is present as head  7110 , which extends outward past the side  7300 , as well as bottom  7200 . In this Figure, the plunger  7000  is approximately cylindrical, so there is only one side  7300 , but if the plunger were shaped differently it could have more than one side. On the side  7300  is a first ridge  7310  located proximate to the bottom  7200  of the plunger  7000  and a second ridge  7320  located proximate to the top, which is present as head  7110  of the plunger  7000 . In this Figure, first ridge  7310  and second ridge  7320  are continuous around the entire side  7300  of plunger  7000 , however other configurations are possible. For example, first ridge  7310  could be first set of multiple ridges the same distance from bottom  7200 . In the same way, second ridge  7320  could be a second set of multiple ridges the same distance from the top, which is in the form of head  7110 . 
       FIG. 7 b    is a detail of second ridge  7320  and side  7300  shown from a cross-section cut-away perspective. Second ridge  7320  extends second width W 2  from side  7300  and has a profile that is substantially rotationally symmetric about axis X 2 . Axis X 2  is substantially normal to side  7300 , and forms angle A 2  with side  7300 . Angle A 2  is 90° in this Figure, though other substantially normal angles are possible. Second width W 2  is equal to or less than the notch depth of the housing with which plunger  7000  is to be used. 
       FIG. 7 c    detail of first ridge  7310  and side  7300  shown from a cross-section cut-away perspective. First ridge  7310  extends first width W 1  from side  7300  and is has a profile that is substantially rotationally symmetric about axis X 1 . Axis X 1  is substantially normal to side  7300 , and forms angle A 1  with side  7300 . Angle A 1  is 90° in this Figure, though other substantially normal angles are possible. Second width W 1  is equal to or less than the notch depth of the housing with which plunger  7000  is to be used. 
       FIG. 8A  is a three-quarter bottom view of microarray carrier  8000 , including microarray holder  8100  as shown in  FIG. 8A  as well as microneedle patch  8200 . Microneedle patch  8200  includes a central portion  8210  featuring a plurality of microneedles  8211  disposed on flexible backing  8220 . While the plurality of central portion  8210  is shown as being roughly circular, other shapes are possible. Further, whereas the plurality of microneedles  8211  are shown as being arranged in a particular manner, other arrangements are possible. Any suitable number of microneedles can be used, and the microneedles may be solid, hollow, or a mixture of solid and hollow. When the microneedles are solid microneedles, such as those described in U.S. Patent Application Publication No. US2005/0246214, then the microneedle patch  8200  typically has 90 to 1,200 microneedles, such as greater than 200 microneedles, greater than 300 microneedles, greater than 400 microneedles, less than 500 microneedles, or less than 400 microneedles on the patch, although any desired number of microneedles can be used. When the microneedles are hollow, such as those described in U.S. Patent Application Publication No. US2016/0151616, then the microneedle patch  8200  typically has 3 to 30 microneedles, most often 12 microneedles, although any desired number of microneedles can be used. 
       FIG. 8B  is a three-quarter bottom view of microarray holder  8100 , featuring tabs  8101 ,  8102 ,  8103 , and  8104 , which can serve to retain a microneedle patch, though no microneedle patch is shown in this Figure. Other elements for restraining a microneedle patch, such as one or more ridges or notches, could be used in a related configuration. Handle  8110  is a convenient feature for manipulating microarray holder  8100 , for example, for placing it within a housing as described herein. 
       FIG. 9A  is a cut-away side view of assembled microarray applicator  9000  featuring housing  2000  (shown separately in  FIG. 2 ) and plunger  7000  (shown separately in  FIG. 7A ). Plunger  7000  is in a first position, wherein first ridge  7310  of plunger  7000  is engaged with notch  2320  of housing  2000 . Second ridge  7320  of plunger  7000  is outside housing  2000 .  FIG. 9B  is a blow-up showing the interaction of first ridge  7310  and notch  2320  in more detail. Bottom  7200  of plunger  7000  does not extend below first major surface  2100  of housing  2000 . 
     In use, pressing plunger  7000  in the direction of first major surface  2100  of housing  2000  with sufficient force to disengage first ridge  7310  of plunger  7000  is engaged with notch  2320  of housing  2000  can move plunger  7000  to a second position. 
       FIG. 9C  is a cut-away side view of assembled microarray applicator  9000  featuring housing  2000  (shown separately in  FIG. 2 ) and plunger  7000  (shown separately in  FIG. 7A ). Plunger  7000  is in a second position, wherein second ridge  7320  of plunger  7000  is engaged with notch  2320  of housing  2000 . Bottom  7200  of plunger  7000  extends below first major surface  2100  of housing  2000 . 
       FIG. 10A  is a cut-away side view of assembled microarray applicator  10000 , which is similar to microarray applicator  9000  as shown in  FIG. 9A  but also includes microarray device  8000 , which is retained within housing  2000  by virtue of microarray holder  8100  being engaged with holder  2400 . Microarray patch  8200  and flexible backing  8220  are positioned such that the central portion  8210  has microneedles  8211  protrude in the direction opposite from the bottom  7200  of plunger  7000 . Bottom  7200  of plunger  7000  sits on or, more commonly, slightly above microarray patch  8200 . In this Figure, plunger  7000  is in a first position, having first ridge  7310  engaged with notch  2320 . Handle  8110  (not shown) is preferably present as a component of microarray holder  8100  for ease of use. 
       FIG. 10B  is a cut-away side view of assembled microarray applicator  10000  after activation, wherein plunger  7000  is in a second position such that second ridge  7320  is engaged with notch  2320 . Here, bottom  7200  of plunger  7000  extends below first major surface  2100  of housing  2000 , and has ejected microarray patch  8200 , thereby applying microneedles  8211  to substrate  10100 , which is typically the skin of a subject. In practice, a user can maintain contact between microneedles  8211  and substrate  10100  by continuing to apply pressure on plunger  7000 . 
     Once microarray patch  8200  has been ejected from housing  2000 , the microarray applicator can be reused. To do so, microarray holder  8100  can be removed from holder  2400 , for example by using handle  8110  (not shown in  FIGS. 10A and 10B ). Plunger  7000  can then be moved from the second position to the first position by pushing on bottom  7200  of plunger  7000  until first ridge  7310  engages with notch  2320 . 
     The applicator as described herein is inexpensively manufactured, for example, all of the components can be made with simple dies by extruding inexpensive plastics such as polypropylene. Thus, the applicator is economical to be used as a single-use device. It can also be re-used, in which case there is little chance of requiring expensive maintenance or repair because it does not contain any complex parts. Further, because it can be easily used by an operator without the need for complex priming steps, it can be viable for an operator who is not a medical professional to use the disclosed applicator, allowing easy application of a microneedle patch without the need for a medical professional to administer it.