The present invention relates to a system and method for tool feedback sensing. More particularly, the present invention relates to feedback sensing provided with tools for assisting with microneedle application procedures.
Only a limited number of molecules with demonstrated therapeutic value can be transported through the skin, even with the use of approved chemical enhancers. The main barrier to transport of molecules through the skin is the stratum corneum (the outermost layer of the skin).
Devices including arrays of relatively small structures, sometimes referred to as microneedles or micro-pins, have been disclosed for use in connection with the delivery of therapeutic agents and other substances through the skin and other surfaces. The devices are typically pressed against the skin in an effort to pierce the stratum corneum such that the therapeutic agents and other substances can pass through that layer and into the tissues below.
Microneedle arrays can be used in conjunction with an applicator device capable of being used a number of different times. The applicator device can include a removable collar for holding the microneedle array prior to deployment. The collar can be reusable or disposable. The microneedle arrays are generally used once and then discarded. The arrays are typically manufactured in a flat sheet-like configuration and temporarily attached to the applicator device using, for example, an adhesive.
Devices exist in the market for making measurement of skin properties, such as Cutometers (skin elasticity), Reviscometers (skin construction), and contact Tonometers (time to rebound from a given deflection), but the suitability of these measurements for use in effectively characterizing microneedle application sites is not known.
Research involving microneedle application may be conducted at application sites on different skin surfaces. For instance, tests may be performed involving microneedle arrays applied to particular skin target areas (e.g., forearms, buttocks, biceps, etc.) of a selected sample of like persons or to persons differing in some way (e.g., by age, race, gender, etc.) or to the skin of different species of test subjects.
The process of consistent use of microneedle application technology presents numerous challenges. Operation of microneedle applicator devices by operators, such as healthcare providers, can be problematic. Operator error, for example, can result in improper microneedle array deployment, which can undermine desired molecule transport. It is believed that proper applicator device positioning can affect microneedle array deployment. However, it is difficult to help ensure proper applicator device positioning. Additional problems are faced in research contexts. Variations across different application sites present difficulties in gathering reliable data from research tests, and in reliably applying collected research data to other contexts.
In one aspect, the present invention relates to a microneedle application device for moving a microneedle array toward a target skin location includes a feedback sensor. The feedback sensor is operably connected to the microneedle application device, and is capable of generating an output corresponding to forces between the target skin location and the microneedle application device.
In another aspect, the present invention relates to a method of microneedle application. The method comprises providing a microneedle applicator device, providing a microneedle array that is initially mounted to the microneedle applicator device, positioning a locating portion of the microneedle applicator device in contact with skin to substantially define a target application site on the skin for application of the microneedle array, sensing a force between the target application site and a first portion of the microneedle applicator device, positioning the microneedle applicator device such that the microneedle array can be moved into contact with the skin along a path that is substantially orthogonal relative to the target application site, and moving the microneedle array toward the target application site.
In another aspect, the present invention relates to a method of positioning a tool for assisting with microneedle application procedures. The method comprises placing the tool in contact with a target site, and sensing a pushback force of the target site against the tool.
In another aspect, the present invention relates to an applicator system including a microneedle application device and a force sensing element. The microneedle application device has a portion adapted for skin contact at least prior to microneedle application. The force sensing element is capable of sensing force between the portion of the microneedle applicator adapted for skin contact and a target application site.
In another aspect, the present invention relates to a tool for sensing forces between the tool and a skin surface. The tool includes a housing having a force application portion, a contact portion, a support, and a sensor. The contact portion is supported by the housing, and is capable of contacting the skin surface to substantially define a target location. The support is supported by the housing, and is capable of reaching the target location. The sensor is disposed between the target location and a first portion of the tool, and is capable of sensing force.
The above summary is not intended to describe each disclosed embodiment or every implementation of the present invention. The figures and the detailed description, which follow, more particularly exemplify illustrative embodiments.
While the above-identified drawing figures set forth several embodiments of the invention, other embodiments are also contemplated, as noted in the discussion. In all cases, this disclosure presents the invention by way of representation and not limitation. It should be understood that numerous other modifications and embodiments can be devised by those skilled in the art, which fall within the scope and spirit of the principles of the invention. The figures may not be drawn to scale. Like reference numbers have been used throughout the figures to denote like parts.
The present invention relates to providing feedback for tools such as microneedle array application devices, as well as diagnostic instruments used in microneedle array application research and training (which may be configured to mimic or simulate typical microneedle application devices). One or more sensors are provided on the tool for sensing forces between the tool and a surface (such as a target skin surface) against which the tool is positioned. An output of the sensed forces can be provided. In some embodiments with multiple sensors, feedback provided according to the present invention permits an indication of how desirably orientated the tool is relative to the surface against which it is positioned. In addition, the present invention can be used for determining ideal locations on the body for application of microneedles.
Aspects of the present invention can be used in conjunction with a variety of tools, though particular advantages are provided for patch application devices. Patches can be used for transdermal delivery of molecules, and can carry microneedle arrays, which have utility for the delivery of large molecules that are ordinarily difficult to deliver by passive transdermal delivery. As used herein, “array” refers to the medical devices described herein that include one or more structures capable of piercing the stratum corneum to facilitate the transdermal delivery of therapeutic agents or the sampling of fluids through or to the skin. “Microstructure,” “microneedle” or “microarray” refers to the specific microscopic structures associated with the array that are capable of piercing the stratum corneum to facilitate the transdermal delivery of therapeutic agents or the sampling of fluids through the skin. By way of example, microstructures can include needle or needle-like structures as well as other structures capable of piercing the stratum corneum.
When the patch application devices are to be used for piercing the stratum corneum in preparation for transdermal drug delivery, the height of the microneedles is preferably sufficient to pass through the stratum corneum. It is also, however, preferable that the height of the microneedles is not sufficiently large to cause significant pain when inserted at a delivery site. In some instances, microneedles of the present invention may have a height of about 250 micrometers or less. In some instances, microneedles of the present invention may have a height of about 100 micrometers or more.
The collar 40 defines an outward-facing contact portion 42. In one embodiment, the collar 40 is detachable from the housing 34, and can be disposable or reusable. As shown in
A driver 50 capable of storing energy engages the shaft 48 of the piston 44, and can accelerate the piston 44 to a desired velocity. For example, the driver 50 may be in the form of a mechanical spring (e.g., a coil spring, leaf spring, etc.), compressed resilient member (e.g., rubber, etc.), compressed fluids (e.g., air, liquids, etc.), piezoelectric structure, electromagnetic structure, etc. The collar 40 can hold a patch 52, carrying a microneedle array, prior to patch application.
In operation, the microneedle application device 30 is positioned with the collar 40 near a desired application site. The contact portion 42 of the collar 40 is placed in contact with the skin surface 32, and the contact portion 42 defines a target patch application site 54 on the skin surface 32. A user will typically apply some force to the microneedle application device 30 at the gripping portion 36 of the housing 34. At least a portion of that force is generally transmitted through the collar 40 to the skin 32, and that force is referred to as a “pushdown force”.
A “dome” 56 is generally created at the target site 54, as the skin 32 responds to the pushdown force. This “dome” has parameters of height and firmness. Both of these parameters of the dome are dependent upon the force applied to the applicator during microneedle application device 30 positioning. It is believed that the depth of penetration of a microneedle array is related to the application site, i.e., soft and fatty areas of a body vs. firm muscular areas of a body. Skin characteristics vary across species, and it is believed that particular characteristics of skin will vary across individual test subjects and across selected application sites on individual test subjects. Such variations can affect characteristics of the dome 56. In addition, a “pushback force” is exerted by the skin 32 in response to the pushdown force. The pushback force is generally directed in a direction directly opposed to the direction of the pushdown force, although specific relationships can be complex and will vary depending on the particular application site.
In the embodiment shown in
In the microneedle application device 30, the piston 44 is moveable between a stored position and an extended position. In the stored position, energy is stored in the driver 50, and an actuator 38 secures the piston 44 in its stored position. The actuator 38 allows an operator to trigger the release of energy stored in the driver 50 to accelerate the piston 44 through the collar 40 and toward the patch 52
The microneedle application device 30 can be used to deliver the microneedle array patch 52 to the skin surface 32, in order to pierce the stratum corneum at the target application site 54 on a patient's skin. For example, the patch application device may be used to deliver drugs (including any pharmacological agent or agents) through the skin in a variation on transdermal delivery, or to the skin for intradermal or topical treatment, such as vaccination. Alternatively, the microneedle array patch 52 may be used to pierce the stratum corneum before or after a pharmacological agent is applied to the skin surface in a separate step, thus being used as a pre- or post-treatment step.
A desired patch application path 78 is defined through the collar 40. The path 78 is substantially perpendicular to a plane in which the microneedle array 76 is retained by the obstructions 70 within the collar 40, and is generally perpendicular to the target application site 54. It is desired that the patch 52 contact the target application site 54 with the patch 52 as close to parallel with the skin surface 32 as possible in order to promote proper microneedle array deployment and proper microneedle penetration of the stratum corneum.
In operation, the patch 52 is moved along the patch application path 78. This patch movement can be accomplished by mechanically pushing the patch 52 with the piston 44. In alternative embodiments, the microneedle application device 30 can use other means for moving the patch 52. For example, the patch 52 can be moved pneumatically, without contacting a piston.
While feedback provided according to the present invention is useful at the time of microneedle application, such feedback is also useful in broader contexts, including training and research settings that may precede or follow patch application. For instance, feedback sensing can be accomplished with purely diagnostic tools.
As shown in
The diagnostic tool 100 further includes a sensor 58 positioned at an interior portion along the support structure 102 and at least one sensor 80 positioned at the contact portion 42 of the collar 40. Sensor locations shown in
Although various embodiments are illustrated in the
In addition, the system 118 can include a lockout mechanism, such as lockout 128. The lockout 128 can prevent an operator from applying a patch unless magnitude of a sensed applied force is within a preferred range. Such a preferred range can consist of a single force value for sensor configurations such as that shown and described with respect to
It will be recognized that components of the system 118 can be wholly contained on or within a tool, or one or more components can be located externally. Components of the system 118 can be connected by a physical or wireless (e.g., radio wave) connection, and can include transmission of data and signals over a network or the Internet.
In an alternative embodiment, the indicator 126A can provide an indication of force sensed at multiple locations. For instance, meter 152 can indicate force sensed at a collar of a tool (see, e.g., sensor region 108 of
Other indicators can be used according to the present invention. For example, indicators can provide auditory output, such as from a sound generator (buzz, squeal, click, etc.) or enunciator (e.g., a voice output). The indicator can also provide an indication of force by varying the intensity of an output (e.g., light or sound intensity).
The indicator can be directly connected to the tool, or can be remotely located. For instance, with the system 118 shown and described with respect to
The ranges and limits of indicators can be set according to a value meaningful for the particular application, for instance, at a value that ensures a high degree of confidence for drug delivery by microneedle arrays. Specific values will vary depending on factors such as application device configuration, microneedle array configuration, molecules to be delivered, etc.
The present invention allows analysis of sensed force data.
The particular ranges 204, 230, 244, 280 of acceptable forces for microneedle application may vary and might depend on a number of factors including, but not limited to, the size, number, and shape of the microneedles, the type and amount, if any, of pharmacological agent being applied, the type and location of the skin surface, and the desired therapeutic response.
The present invention permits more consistent microneedle array application by providing feedback as to application parameters. For instance, where sensors are provided on both a collar and a piston of a microneedle application device, pushback force can be sensed and measured in relation to skin doming at a specific target site. In addition, for example, the recoil effect, if any, during patch application can be sensed and assessed.
Sensed data can assist in real-time site selection and patch application procedures. Real-time feedback allows an operator to obtain reliable characterizations of application procedure parameters without relying on muscle memory or other training-dependent factors for consistent and reliable patch application. Sensed data can also be used, in some situation, to adjust forces applied to move a patch toward a target application site, such as by selecting an appropriate applicator or in conjunction with adjusting a variable force driver.
Thus, the present invention provides the ability to measure and diagnose parameters associated with a particular target site for microneedle application as they directly apply to the chosen application device (or tool). This is advantageous over other devices as it allows for characterization of an application site by determining the specific site variable of skin pushback force relative to applied force. The present invention can also be used to assess the angle of application, i.e., the orientation of the tool, to assist the user in positioning the tool perpendicular to the target site by assuring that generally even pressure is applied over three or more force sensor regions at a contact portion of the tool.
In addition, the present invention has advantages for use in pre-clinical testing on non-human animals in order to better correlate research data to human testing and other subsequent application contexts. For all the foregoing reasons, the present invention has advantages over current technology in its ability to assess a site specifically for microneedle application. The specified advantages, however, should not be considered limiting in any way to the overall scope or utility of the invention.
Although the present invention has been described with reference to several alternative embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention. For instance, tools contemplated for use with the system and method of feedback sensing of the present invention can include a variety of applicators, such as applicators of any type of patch. In addition, all the graphs of
The present application claims priority to U.S. Provisional Application Ser. No. 60/669,133, filed on Apr. 7, 2005, which is incorporated herein in its entirety.
Filing Document | Filing Date | Country | Kind | 371c Date |
---|---|---|---|---|
PCT/US2006/013608 | 4/7/2006 | WO | 00 | 9/28/2007 |
Publishing Document | Publishing Date | Country | Kind |
---|---|---|---|
WO2006/108185 | 10/12/2006 | WO | A |
Number | Name | Date | Kind |
---|---|---|---|
3034507 | McConnell et al. | May 1962 | A |
3072122 | Rosenthal | Jan 1963 | A |
3123212 | Taylor et al. | Mar 1964 | A |
3136314 | Kravitz | Jun 1964 | A |
RE25637 | Kravitz et al. | Sep 1964 | E |
3221740 | Rosenthal | Dec 1965 | A |
3246647 | Taylor et al. | Apr 1966 | A |
3322121 | Banker | May 1967 | A |
3466131 | Arcudi | Sep 1969 | A |
3510933 | Taylor et al. | May 1970 | A |
3512520 | Cowan | May 1970 | A |
3596660 | Melone | Aug 1971 | A |
3675766 | Rosenthal | Jul 1972 | A |
3678150 | Szumski et al. | Jul 1972 | A |
3688764 | Reed et al. | Sep 1972 | A |
3905371 | Stickl et al. | Sep 1975 | A |
3964482 | Gerstel et al. | Jun 1976 | A |
4109655 | Chacornac | Aug 1978 | A |
4237906 | Havstad et al. | Dec 1980 | A |
4304241 | Brennan | Dec 1981 | A |
4360016 | Sarrine | Nov 1982 | A |
4453926 | Galy | Jun 1984 | A |
4503856 | Cornell et al. | Mar 1985 | A |
4517978 | Levin et al. | May 1985 | A |
4637403 | Garcia et al. | Jan 1987 | A |
4858607 | Jordan et al. | Aug 1989 | A |
4869249 | Crossman et al. | Sep 1989 | A |
4920977 | Haynes | May 1990 | A |
4924879 | O'Brien | May 1990 | A |
5209967 | Wright et al. | May 1993 | A |
5250023 | Lee et al. | Oct 1993 | A |
5318584 | Lange et al. | Jun 1994 | A |
5368047 | Suzuki et al. | Nov 1994 | A |
5402798 | Swierczek et al. | Apr 1995 | A |
5487726 | Rabenau et al. | Jan 1996 | A |
5573626 | Rossini et al. | Nov 1996 | A |
5611806 | Jang | Mar 1997 | A |
5879326 | Godshall et al. | Mar 1999 | A |
5904978 | Hanrahan et al. | May 1999 | A |
5983136 | Kamen | Nov 1999 | A |
6050988 | Zuck | Apr 2000 | A |
6132755 | Eicher et al. | Oct 2000 | A |
6256533 | Yuzhakov et al. | Jul 2001 | B1 |
6293925 | Safabash et al. | Sep 2001 | B1 |
6312612 | Sherman et al. | Nov 2001 | B1 |
6322808 | Trautman et al. | Nov 2001 | B1 |
6334856 | Allen et al. | Jan 2002 | B1 |
6440096 | Lastovich et al. | Aug 2002 | B1 |
6454755 | Godshall | Sep 2002 | B1 |
6503231 | Prausnitz et al. | Jan 2003 | B1 |
6532386 | Sun et al. | Mar 2003 | B2 |
6537242 | Palmer | Mar 2003 | B1 |
6547755 | Lippe et al. | Apr 2003 | B1 |
6589202 | Powell | Jul 2003 | B1 |
6591124 | Sherman et al. | Jul 2003 | B2 |
6595947 | Mikszta et al. | Jul 2003 | B1 |
6603998 | King et al. | Aug 2003 | B1 |
6623457 | Rosenberg | Sep 2003 | B1 |
6656147 | Gertsek et al. | Dec 2003 | B1 |
6713291 | King et al. | Mar 2004 | B2 |
6743211 | Prausnitz et al. | Jun 2004 | B1 |
6797276 | Glenn et al. | Sep 2004 | B1 |
6855131 | Trautman et al. | Feb 2005 | B2 |
6881203 | Delmore et al. | Apr 2005 | B2 |
6890319 | Crocker | May 2005 | B1 |
6908453 | Fleming et al. | Jun 2005 | B2 |
6931277 | Yuzhakov et al. | Aug 2005 | B1 |
20020032415 | Trautman et al. | Mar 2002 | A1 |
20020058902 | Kollias et al. | May 2002 | A1 |
20020082543 | Park et al. | Jun 2002 | A1 |
20020087182 | Trautman et al. | Jul 2002 | A1 |
20020091357 | Trautman et al. | Jul 2002 | A1 |
20020095134 | Pettis et al. | Jul 2002 | A1 |
20020111600 | Cormier et al. | Aug 2002 | A1 |
20020123675 | Trautman et al. | Sep 2002 | A1 |
20020138049 | Allen et al. | Sep 2002 | A1 |
20020169416 | Gonnelli et al. | Nov 2002 | A1 |
20020177858 | Sherman et al. | Nov 2002 | A1 |
20020188245 | Martin et al. | Dec 2002 | A1 |
20020198509 | Mikszta et al. | Dec 2002 | A1 |
20030050602 | Pettis et al. | Mar 2003 | A1 |
20030083641 | Angel et al. | May 2003 | A1 |
20030135158 | Gonnelli | Jul 2003 | A1 |
20030181863 | Ackley et al. | Sep 2003 | A1 |
20030199812 | Rosenberg | Oct 2003 | A1 |
20030199823 | Bobroff et al. | Oct 2003 | A1 |
20030208167 | Prausnitz et al. | Nov 2003 | A1 |
20040049150 | Dalton et al. | Mar 2004 | A1 |
20040077994 | Lastovich et al. | Apr 2004 | A1 |
20040138612 | Shermer et al. | Jul 2004 | A1 |
20040176732 | Frazier et al. | Sep 2004 | A1 |
20040181203 | Cormier et al. | Sep 2004 | A1 |
20050025778 | Cormier et al. | Feb 2005 | A1 |
20050027242 | Gabel et al. | Feb 2005 | A1 |
20050065463 | Tobinaga et al. | Mar 2005 | A1 |
20050065466 | Vedrine | Mar 2005 | A1 |
20050065472 | Cindrich et al. | Mar 2005 | A1 |
20050096586 | Trautman et al. | May 2005 | A1 |
20050106226 | Cormier et al. | May 2005 | A1 |
20050137525 | Wang et al. | Jun 2005 | A1 |
20050261631 | Clarke et al. | Nov 2005 | A1 |
Number | Date | Country |
---|---|---|
407063 | Jan 1991 | EP |
1080986 | Aug 1967 | GB |
2064329 | Jun 1981 | GB |
2221394 | Feb 1990 | GB |
WO 9610630 | Apr 1996 | WO |
WO 0056213 | Sep 2000 | WO |
WO 0136037 | May 2001 | WO |
WO 2004020034 | Mar 2004 | WO |
WO 2004021882 | Mar 2004 | WO |
WO 0551455 | Jun 2005 | WO |
WO 0551476 | Jun 2005 | WO |
WO 0565765 | Jul 2005 | WO |
WO 2005123173 | Dec 2005 | WO |
WO 2006055795 | May 2006 | WO |
WO 2006055802 | May 2006 | WO |
WO 2006108185 | Oct 2006 | WO |
WO 2007002521 | Jan 2007 | WO |
Entry |
---|
Daddona, Current Opinion in Drug Discovery and Development 1999 2(2);168-171. |
Henry et al. J. Pharm.Sci., 1998, 87,8,922-925. |
Kaushik et al. Anesthesia Analg., 2001, 92, 502-504. |
McAllister et al. Annual Review of Biomedical Engineering, 2000, 2, 289-313. |
McAllister et al. Proceed. Int'l. Symp. Control Release of Bioactive Material, 26, (1999), CRS, 192-193. |
Number | Date | Country | |
---|---|---|---|
20080208146 A1 | Aug 2008 | US |
Number | Date | Country | |
---|---|---|---|
60669133 | Apr 2005 | US |