Abstract:
A medical device includes a sensor that is configured to measure a property of an outer layer of an anatomical body surface. The sensor includes a source probe configured to stimulate a local surface of the outer layer of an anatomical body surface. The sensor also includes a detector configured to measure a response of the outer layer resulting from the source probe stimulation. A controller coupled to the source probe and the sensor drives the source probe using a tailored stochastic sequence and determines the property of the outer layer using the measured response received from the detector. The sensor can be used with medical devices, such as drug delivery devices including microneedle transport devices and needleless injection devices.

Description:
RELATED APPLICATIONS 
     This application is a divisional of U.S. application Ser. No. 10/657,724, filed Sep. 8, 2003 now U.S. Pat. No. 7,530,975, which is a Continuation of U.S. application Ser. No. 10/656,806, filed on Sep. 5, 2003 now abandoned which claims the benefit of U.S. Provisional Application Nos. 60/409,090, filed Sep. 6, 2002 and 60/424,114, filed Nov. 5, 2002. 
     The entire teachings of the above applications are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     Injection of a liquid such as a drug into a human patient or an agriculture animal is performed in a number of ways. One of the easiest methods for drug delivery is through the skin which is the outermost protective layer of the body. It is composed of the epidermis, including the stratum corneum, the stratum granulosum, the stratum spinosum, and the stratum basale, and the dermis, containing, among other things, the capillary layer. The stratum corneum is a tough, scaly layer made of dead cell tissue. It extends around 10-20 microns from the skin surface and has no blood supply. Because of the density of this layer of cells, moving compounds across the skin, either into or out of the body, can be difficult. 
     The current technology for delivering local pharmaceuticals through the skin includes methods that use needles or other skin piercing devices. Invasive procedures, such as use of needles or lances, effectively overcome the barrier function of the stratum corneum. However, these methods suffer from several major disadvantages: local skin damage, bleeding, and risk of infection at the injection site, and creation of contaminated needles or lances that must be disposed. Further, when these devices are used to inject drugs in agriculture animals, the needles break off from time to time and remain embedded in the animal. 
     Needleless injection devices have been proposed to overcome the problems associated with needles, but the proposed devices present different problems. For example, some needleless injection devices rely on spring actuators that offer limited control. Others use solenoids, compressed air or hydraulic actuators also offer limited control. 
     SUMMARY OF THE INVENTION 
     Skin sensor apparatus and methods described herein use specially tailored stimulation to effectively measure one or more properties of the surface of an anatomical body, such as the compliance gain and/or stiffness of skin. 
     A medical device includes a sensor configured to measure a property of an outer layer of an anatomical body surface. The sensor includes a source probe configured stimulate a local surface of the outer layer of an anatomical body surface. The sensor also includes a detector configured to measure a response of the outer layer resulting from the source probe stimulation. Further, the device includes a controller coupled to the sensor. The controller drives the source probe using a tailored stochastic sequence. The controller then determines the property of the outer layer using the measured response received from the detector. 
     The body surface can be the skin of a subject, or an internal body surface. The body surface can be modeled as a second order mechanical system. Further, the property of the outer layer can be determined using system identification techniques. 
     The source probe can include a voice coil for stimulating the local surface of the outer layer. For example the voice coil can be coupled to the outer layer and driven at a frequency to displace the surface. The detector measures displacement of the body surface, for example, using an accelerometer. In one embodiment, the detector includes a linear differential variable transducer detecting displacement of the body surface. In some embodiments, the detector further includes a strain gauge for measuring a static displacement of the body surface. 
     The medical device can be a drug injection device. The drug injection device is coupled to the sensor and injects a drug into an anatomical body in response to the determined property of the outer layer. For example, the device can include a servo-controller coupled to a delivery device for delivering a pharmaceutical. The servo-controller adjusts the delivery characteristics of the delivery device based on the surface properties. In one embodiment, the drug injection device is a needleless injector. 
     A device for injecting drug into a biological body includes a drug injector for holding the drug to be delivered to the body. The device also includes a skin sensor that measures skin properties of the body and a servo-controller coupled to the drug injector and the skin sensor. The servo-controller adjusts the injection pressure of the drug injector to selectively deliver the drug to the body based on the skin properties. In some embodiments, the skin sensor measures the properties of the body using a tailored stochastic sequence. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. 
         FIG. 1A  is a perspective view of a drug delivery device in accordance with the invention. 
         FIG. 1B  is a side view of the drug delivery device of  FIG. 1A . 
         FIG. 1C  is an end view of the drug delivery device taken along the line  1 C- 1 C of  FIG. 1B . 
         FIG. 2  is a perspective view of the drug delivery device of  FIG. 1A  with a controller and energy source. 
         FIG. 3A  is a graph of the time response of a shape memory alloy fiber of the drug delivery device of  FIG. 1A  for a high strain. 
         FIG. 3B  is a graph of the time response of the shape memory alloy fiber of the drug delivery device of  FIG. 1A  when the fiber is subjected to a potential as a quick pulse. 
         FIGS. 4A-4C  are respectively side, front, and top views of a hand-held drug delivery device. 
         FIG. 4D  is a perspective view of the drug delivery device shown in  FIGS. 4A-4C . 
         FIG. 5A  is a cross-sectional view of the drug delivery device taken along the line  5 A- 5 A of  FIG. 1C  prior to delivery of a drug. 
         FIG. 5B  is a cross-sectional view of the drug delivery device of  FIG. 1A  during drug delivery. 
         FIG. 6A  is a perspective view of an alternative embodiment of the drug delivery device in accordance with the invention. 
         FIG. 6B  is a side view of the drug delivery device of  FIG. 6A . 
         FIG. 6C  is top view of the drug delivery device taken along the line  6 C- 6 C of  FIG. 6B . 
         FIG. 6D  is front view of the drug delivery device taken along the line  5 D- 5 D of  FIG. 6B . 
         FIG. 7A  is a perspective view of a drug vile for the drug delivery device of  FIG. 6A . 
         FIG. 7B  is a cross-sectional view of the drug vile of  FIG. 7A . 
         FIG. 8  is a perspective view of the drug delivery device of  FIG. 6A  with a controller and energy source. 
         FIG. 9A  is a cross-sectional view of the drug delivery device taken along the line  9 A- 9 A of  FIG. 6D  prior to delivery of a drug. 
         FIG. 9B  is a cross-sectional view of the drug delivery device during drug delivery. 
         FIG. 10  is cross-sectional view of another alternative embodiment of the drug delivery device in accordance with the invention. 
         FIG. 11  illustrates the drug delivery device of  FIG. 10  with a protective sterile ribbon in accordance with the invention. 
         FIGS. 12A and 12B  illustrate yet another alternative embodiment of the drug delivery device in accordance with the invention. 
         FIG. 13  illustrates the drug delivery device with a sensor used to detect properties of the skin in accordance with the invention. 
         FIG. 14  is a block diagram of an alternative embodiment of the sensor used to detect properties of the skin in accordance with the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     A description of preferred embodiments of the invention follows. 
     Referring to  FIGS. 1A-1C , there are shown various views of a drug delivery device used to inject a liquid formulation of an active principle, for example, a drug, into biological body such as an agriculture animal or human being. The delivery device is generally identified as  10  in the illustrated embodiment as well as in other embodiments described later. The drug is initially contained in a chamber  12  ( FIG. 5A ) and is injected out through an orifice or output port  14  into the body. 
     A nozzle is typically used to convey the drug to the skin at the required speed and diameter to penetrate the skin as required. The nozzle generally contains a flat surface, such as the head  17  that can be placed against the skin and an orifice  14 . It is the inner diameter of the orifice  14  that controls the diameter of the drug stream. Additionally, the length of an aperture, or tube, defining the orifice  14  also controls the injection pressure. In some embodiments, a standard hypodermic needle is cut to a predetermined length and coupled to the head. One end of the needle is flush, or slightly recessed, with respect to the surface of the head  17  that contacts the skin to avoid puncturing the skin during use. The internal diameter of the needle (e.g., 100 ÿm) defines the diameter of the aperture, and the length of the needle (e.g., 5 mm) together with the aperture dimension controls the resulting injection pressure, for a given applicator pressure. In other embodiments, a hole can be drilled directly into the head  17  to reduce assembly steps. In general, the length of the orifice is selectable, for example ranging from 500 ÿm to 5 mm, while its diameter can range from 80 ÿn to 200 ÿm. 
     The device  10  includes a guide tube  16  in which a piston  18  is positioned. An interchangeable head  17  is attached at an enlarged end  19  of the tube  16  with a set of screws  21 . One end of the piston  18 , along with the inside of the enlarged end  19  and head  17  define the chamber  12 , and a push block  22  is attached at the other end of the piston  18 . Although the piston  18  forms a clearance seal with the tube  16 , a seal ring can be placed about the piston  18  to prevent drug from escaping from the chamber  12  between the piston  18  and the tube  16 . Attached on the outside of the push block  22  is an electrical contact plate  24 . Another contact plate  26  is positioned between the interchangeable head  17  and the enlarged end  19 . 
     In some embodiments, the guide tube  16  includes linear bearings to reduce the friction of the piston  18 . Preferably, the piston  18  is rigid to avoid buckling under the force exerted by the actuator. Further, the piston  18  is light weight to reduce its inertia ensuring a rapid acceleration upon activation. In one embodiment, the piston  18  is formed from a hollow aluminum rod. Other parts can also be advantageously constructed of light weight materials. For example, the push block  22  can be formed from a machinable poly acetal. 
     In addition to the contact plates  24  and  26 , an actuator  28  includes one to six or more wires  30  positioned about the tube  16  and parallel to one another. One end  32  of each wire  30  is attached to the contact plate  24  through the push block  22 , and another end  34  of the wire  30  is attached to a respective capstan  36 . The capstan  36 , and the contact plates  24  and  26  are electrically conductive. Hence, the ends  32  and  34  of the wires  30  are electrically connected to each other through the contact plates  24  and  26 , respectively. An insulating collar  38  positioned about the guide tube  20  helps guide the wires  30  through the holes  39  between the enlarged region  19  and the push block  22 . 
     To apply the appropriate tension to the wires  30  and to define the volume of the chamber  12 , a coiled spring  37  is positioned about the piston  18  between the end of the tube  16  and the push block  22 , and the capstans  36  are turned accordingly, much like adjusting the tension in guitar strings. The wires  30  are wrapped around the respective capstans  36  one or more times. As such, the strain near the terminal ends  34  of the wires  30  attached to the capstans  36  are significantly less than the strain along the remainder of the length of the wires  30 . For example, the strain near the terminal end  34  may be about 1% while that of the remainder of the wire may be about 15%. 
     The wires  30  can be secured to the contact plate  24  with capstans, as well. Alternatively, the wires  30  can be attached to one or both contact plates  24  and  26  by other techniques, for example, by electrodeposition as described in U.S. Pat. No. 5,641,391, the entire contents of which are incorporated herein by reference. 
     Alternatively, each wire  30  can be twisted with a respective electrically conductive wire made of, for example, copper or iron. The twisted segment is then bent back, and partially twisted forming a loop, with the partially twisted segment formed of two strands of the wire  30  and two strands of the copper wire. The formed loop can be placed on a pin, for example, or it can be fully twisted and then bent back and partially twisted forming another loop, with the partially twisted segment formed of four strands of the wire  30  and four strands of the copper wire. Again, the formed loop can be placed on a pin to secure the wire  30  to the contact plate  24  and/or  26 . 
     More generally, the wires  30  can be formed from a shape memory material that changes from a first stable state to a second stable state upon excitation. For example, the shape memory material can be a shape memory polymer. Alternatively, or in addition, the shape memory material can be an alloy. In some embodiments, a phase change of the shape memory material occurs when the material is heated. For example, a shape metal alloy can exist with one of two different lattice structures, such that a phase change from one lattice structure to another occurs responsive to the application and/or removal of thermal energy. 
     The wires  30  are made of a suitable material that contracts when heated and can be used as an actuation method. Heating can be accomplished by passing a current through the wire  30 , known as Joule heating. Thus, the current is conducted within the wires  30  after a potential is applied across them. A class of materials that contract when a potential is applied to them includes piezoelectric materials and shape memory alloys. While piezoelectric crystals contract about 1%, shape memory alloys are able to contract approximately 15% or more. The larger contraction of shape memory alloys makes them desirable for the illustrated embodiment. Accordingly, the wires  30  are made of shape memory alloy such as, for example, Ni—Ti (also known as Nitinol), available from Shaped Memory Applications Inc., of San Jose, Calif., and from Dynalloy Inc. of Costa Mesa, Calif., under the Trade Mark FLEXINOL. When a potential is applied across the wires  30  via the contact plates  24  and  26  the wires  30  heat up. As the wires  30  heat up, a phase transformation of the wire material occurs, namely, the wire changes phase from martensite to austenite. This phase transformation causes the wires  30  to contract such that the piston  18  is pushed towards the orifice  14 , thereby forcing the drug from the chamber  12  out the orifice  14 . Preferably, the shape memory alloy is fast acting to provide a sudden force suitable for injecting a drug into a patient&#39;s skin without using a needle. A more detailed description of shape memory alloys and their use is described in U.S. Pat. No. 5,092,901, the entire contents of which are incorporated herein by reference. 
     To use the device  10 , the device is connected to a controller  50  with a pair of leads  52 , and the controller in turn in connected to a capacitor bank  54  with another pair of leads  56 , as illustrated in  FIG. 2 . The controller  50  can be a simple microprocessor, or alternatively a personal computer with multifunction capabilities. The capacitors of the bank  54  are energized through a power source in the controller  50  or by an external power source. Once energized, the capacitors, under the direction of the controller  50 , discharge to apply a potential across the wires  30  via the plates  24  and  26  through the leads  52 . In this manner, the wires  30  are connected together in a parallel configuration, the supply potential being applied equally across the ends of each of the multiple wires  30 . In another embodiment, the wires  30  are connected together in a series configuration. Still other arrangements can be used to apply the potential across the wires  30 , for example, as describe in U.S. application Ser. No. 10/200,574 filed Jul. 19, 2002, by Angel and Hunter, the entire contents of which are incorporated herein by reference. 
     Although any capacitor can be used in the bank  54 , a super capacitor has the advantageous feature of providing a large energy density in a small physical size. Hence the capacitors of the bank  54  can be super capacitors  53  that have a volume from 1.5 ml to 30 ml, preferably 3 ml, and an energy output of 10 J to 1 KJ, preferably 100 J. The current applied to the wires  30  is approximately 100 mAmps to 5 Amps, and the voltage applied to the wires  30  is between about 1 volt to 10 volts. In one embodiment, the applied current is 1 Amp, and the applied voltage is 5 volts. To heat the wires  30  quickly, larger currents of 25 to 100 Amps can be applied. As fast action is required, the power source must also be able to switch large currents with millisecond timing. 
     The amount of force per area generated by the wires  30  is about 235 MN/m 2 . In the illustrated embodiment, the volume of drug initially contained in the chamber  12  is about 200 ÿL to 250 ÿL, and the orifice  14  has a diameter of between about 50 ÿm to 500 ÿm. In some embodiments, the drug volume is up to 500 ÿL. The drug injection velocity is about 150 m/s with a 150 ÿm orifice  14 . Generally, an injection velocity of 100 m/s or greater is required for successful skin penetration (e.g., penetrating skin to a depth of 2 mm) in a stream having a diameter of 100 ÿm. Advantageously, the stream diameter of the needleless injector can be substantially smaller than a typical 24 gauge needle having a diameter of 450 ÿm. 
     The device  10  has a length, L 1 , of approximately 150 mm, and the wires  30  contract about 7 mm when a potential is applied across them. The wires  30  can have circular cross section, in which case each wire  30  has a diameter of approximately 0.025 mm to 2 mm, preferably 380 ÿm. Alternatively, each fiber can have a flat ribbon shape with a thickness approximately in the range 0.025 mm to 0.5 mm and a width of approximately 0.75 mm to 10 mm. Other suitable shape memory alloys include Ag—Cd, Au—Cd, Au—Cu—Zn, Cu—Al, Cu—Al—N, Cu—Zn, Cu—Zn—Al, Cu—Zn—Ga, Cu—Zn—Si, Cu—Zn—Sn, Fe—Pt, Fe—Ni, In—Cd, In—Ti, and Ti—Nb. 
     Referring now to  FIGS. 3A and 3B , there are shown graphs of the time response of wires  30  made from Ni—Ti. Shown in  FIG. 3A  is the response of a wire subjected to a strain of nearly 5%. As can be seen, the contraction time for this wire is about 10 ms. By way of contrast,  FIG. 3B  illustrates a wire subjected to faster pulse than that applied to the wire of  FIG. 3A . With the faster pulse, the fiber experiences a strain of about 1%, with a contraction time of about 1 ms. 
     In use, the device  10  is typically mounted within an applicator that is held by an operator. The applicator can be shaped as a pistol, cylinder or any other suitable geometry. An exemplary applicator is shown in  FIGS. 4A through 4D . In one embodiment, referring to  FIG. 4A , a pistol shaped applicator  400  includes a barrel  405  configured to house the device  10 . The barrel  405  can be a hollow tube or rectangle having a cavity sized to accept the device  10 . Referring to  FIG. 4B , the barrel  405  includes an aperture  420  at one end sized to accept the head  17  of the device  10 . The head  17  protrudes through the aperture  420  to facilitate contact with an animal&#39;s skin. Further, the applicator  400  includes a handle  410  configured to be grasped by an operator. The handle  410  is coupled at one end to the barrel  405 . Additionally, the applicator  400  can include a base  415  coupled to another end of the handle  410 . The base  415  can be configured to house other parts of the needleless injector, such as the power source and/or control unit. The handle  410  can be similarly configured (e.g., hollowed out) to also house parts of the needleless injector. Further, the applicator  400  can include a switch  420 . The switch  420  can be controlled by an operator to operate the device  10  to initiate an injection and/or a filling of the device with a drug. 
     Referring to  FIGS. 5A and 5B , as well as to  FIG. 1A , the operator positions the applicator to place a surface  60  of the head  17  against the skin, S, of the biological body. Prior to the placement of the head  17  against the skin, or while the head  17  is positioned against the skin, the capacitor bank  54  is energized as described above. The operator then triggers the device  10  through the controller  50  to discharge the capacitor bank  54 , thereby applying a potential across the wires  30  which causes them to contract. As the wires  30  contract, they pull the push block  22 , which pushes the piston  18  towards the head  17  to force the drug, D, from the chamber  12  through the orifice  14  into the body. The injection pressure can be as low as 1 MPa or lower or as high as 300 MPa. For comparison, a minimum local pressure of approximately 1.91 MPa is required for piercing skin to a depth of 2 mm using a 100 ÿm diameter needle After the energy in the capacitor bank is depleted, the potential across the wires  30  is removed which causes the wires  30  to extend to their original length as the coiled spring  37  pushes the push block  22  away from the head  17 . The chamber  12  can then be refilled if desired with additional drug to be injected into another body or the same body. 
     Turning now to  FIGS. 6A-6D , there are shown various views of an alternative embodiment of the drug delivery device  10 , where like features are identified by like numerals. Here, the device  10  includes two base portions  70  and  72 . The piston  18  extends through the base portion  72  and through part of the base portion  70 , as shown, for example, in  FIG. 9A . As before, the piston  18  is attached at one end to the push block  22 , which slides back and forth over a surface  76  of the base portion  72 , such that the piston slides back and forth in the base portions. 
     Referring also to  FIGS. 7A and 7B , a removable and/or disposable vial  80  is mounted in the base portion  70 . For example, the vial  80  can be screw mounted to the base portion  70 . The vial  80  is provided with a nozzle, as described above, at one end defining the orifice  14 . The vial  80  also includes a plunger  82  that moves back and forth in the chamber  12  defined within the vial  80 . The plunger  82  abuts the terminal end  84  of the piston  18 . As such, as the piston  18  moves towards the orifice  14 , drug, D, contained in the chamber  12  is expelled through the orifice  14 . In some implementations, the orifice of the drug vial, or the chamber of the embodiment of  FIG. 1A , is sealed with a suitable material prior to use. The seal may be manually removed, or it may be removed by the injection pressure of the drug as it ejects from the vial or chamber. 
     A single length wire  30  is positioned on each side of the base portions  70  and  72  and attached at one end to a lead capstan  90   a , wrapped sequentially around intermediate capstans  90   b ,  90   c ,  90   d , and attached at the other end to a terminal capstan  90   e . To apply the appropriate tension to the wires  30 , the coiled spring  37  is positioned about the piston  18  between the base portion  72  and the push block  22 , and a ratchet mechanism  92  is employed to adjust the tension in the wires  30 . The capstans  90   a ,  90   c , and  90   e  are electrically conductive, and are coupled to respective conductive bars  94  and  96 . The capstans  90   b  and  90   d  are also electrically conductive, and are electrically coupled to respective conductive plates  98  and  100 . The plates  98  and  100  in turn are electrically connected to each other through the push block  22 , but electrically insulated from the piston  18  and base portion  72 . The two bars  94  and  96  are electrically insulated from the base portion  70 . As such, when a potential is applied across the conductive bars  94  and  96 , the potential is also applied across the four segments of each wire  30 . 
     In one implementation, the device  10  of  FIG. 6A  is connected to the controller  50  with the pair of leads  52 , and the controller in turn in connected to the capacitor bank  54  with another pair of leads  56 , as illustrated in  FIG. 8 . As mentioned above, the capacitors of the bank  54  are energized through a power source in the controller  50  or by an external power source. Once energized, the capacitors, under the direction of the controller  50 , discharge to apply a potential across the wires  30  via the conductive bars  94  and  96  through the leads  52 . The wires  30  heat up and contract such that the piston  18  is pushed towards the orifice  14 , thereby forcing the drug D from the chamber  12  of the vial  80  out the orifice  14 . 
     Although shown as blocks, the base portions  70  and  72  can have any suitable geometry which facilitates the use of the device  10  of  FIG. 6A  in a particular application. As mentioned before, the device can be mounted within an applicator that is held by an operator. 
     Referring to  FIGS. 9A and 9B , as well as to  FIG. 6A , to use the device  10 , the operator positions the applicator such that a surface  101  of the vial  80  is placed against the skin, S, of the body. Prior to the placement of the surface  101  against the skin, or while the surface  101  is positioned against the skin, the capacitor bank  54  is energized, as described earlier. The operator then triggers the device  10  through the controller  50  to discharge the capacitor bank  54 , thereby applying a potential across the wires  30  which causes them to contract. As the wires  30  contract, they pull the push block  22  which pushes the piston  18 , which in turn pushes the plunger  82  towards the orifice  14  to force the drug, D, from the chamber  12  through the orifice  14  into the body. After the energy in the capacitor bank is depleted, the potential across the wires  30  is removed which causes the wires  30  to extend to their original length as the coiled spring  37  pushes the push block  22  away from the vial  80 . The chamber  12  can then be refilled if desired with additional drug to be injected into another body. 
     The device  10  of  FIG. 1A  or  5 A can be used as a single-use device or for multiple uses. When used as a multiuse device, the cycle time between uses can be 0.5 seconds or less. 
     For example, there is shown in  FIG. 10  the device  10  of  FIG. 1A  coupled to a reservoir  100  that supplies the chamber  12  with a sufficient amount of drug, D, for each injection, and holds enough drug for approximately 20 to 200 or more injections. Alternatively, individual doses may be provided in a plurality of reservoirs sequentially coupled to the delivery device  10 . A valve  102  is associated with a tube  103  connecting the reservoir  100  with an inlet port  104  of the chamber  12 . The valve  102  is opened and closed under the direction of the controller  50 , or an additional controller, to allow the desired amount of drug into the chamber  12  for each injection. The device  10  of  FIG. 6A  can also be coupled to a similar reservoir that is operated in the manner just described. 
     When the device  10  of  FIG. 10  is in use, the controller  50  instructs the valve  102  to open to allow the drug to flow from the reservoir  100  through the inlet port  104  into the chamber  12 , and, after a prescribed period of time, the controller  50  directs the valve  102  to close so that a desired amount of the drug is held in the chamber  12  for a single injection. 
     Next, or while the chamber  12  is being filled with drug, the operator positions the applicator to place the surface  60  of the head  17  against the skin, S, of the body. Meanwhile, the capacitor bank  54  is energized as described above. The operator then triggers the device  10  through the controller  50  to discharge the capacitor bank  54 , thereby applying a potential across the wires  30  which causes them to contract. As the wires  30  contract, they pull the push block  22  which pushes the piston  18  towards the head  17  to force the drug, D, from the chamber  12  through the orifice  14  into the body. After the energy in the capacitor bank is depleted, the potential across the wires  30  is removed which causes the wires  30  to extend to their original length as the coiled spring  37  pushes the push block  22  away from the head  17 . The controller  50  then instructs the valve  102  to open to refill the chamber  12  with additional drug from the reservoir  100  to be injected into another body. 
     When the device  10  is intended for multiple uses, it may be desirable to provide some type of protective sterile barrier between the head  17  and the skin of the body to eliminate or at least minimize exposing a subsequent body with contaminants from a previous body. 
     For example, there is shown in  FIG. 11  the device  10  provided with a supply of ribbon from a supply roller  110  mounted to the device  10  with a support  112 . A sheet of ribbon  111  passes between the face  60  (see, e.g.,  FIG. 1A ) and the skin, S, of the body. After use, the ribbon  111  is spooled onto a take-up roller  114  that is mounted to the device  10  with a support  116 . The ribbon  111  is wide enough to cover the face  60  such that none of the face  60  makes contact with the skin, S. The ribbon  111  is made of any suitable material that prevents cross-contamination between biological bodies, such as a non-porous flexible material. 
     The operation of the take-up roller  114 , and, optionally, the supply roller  110 , can be controlled by the controller  50 , or an additional controller. Thus, when in use, the device  10  ejects drug from the orifice  14  through the ribbon  111  into the body. After the drug has been injected into the body, additional drug can be supplied from the reservoir  100  according to the techniques described above, while the controller  50  instructs the roller  114  to take up a sufficient amount of ribbon  111  in the direction A, so that the next body is exposed only to a new sterile portion of the ribbon  111  during the injection procedure. 
     In other implementations, a new sterile head  17  is positioned on the device  10  after an injection, while the previous head  17  is disposed in a suitable manner. 
     Referring now to  FIGS. 12A and 12B , there is shown another embodiment of the device  10  suitable for multiuse operations. The device  10  is provided with a series of vials  80  connected together, for example, with a flexible web  120 . Enlarged regions  122  and  124  (see, e.g.,  FIG. 7A ) of the vials  80  engage with a slot  126  of the base portion  70 . Thus, after each injection, a driver  200 , separate from or integral with the device  10 , pulls the web  120 , and hence the vials  80 , in the direction  13  until a vial filled with drug and fed from the top of the base  70  is suitably coupled with the piston  18  for the next injection. The injection procedure proceeds as described earlier, for example, for the embodiment of  FIG. 6A . As such, the device  10  can be used in a “machine-gun” like manner, with new vials being fed through the top of the base  70 , while depleted vials are pulled out from the bottom of the base  70 . The driver  200  can be under the control of the controller  50  or another controller. The vials  80  could be fed and removed from the side of the base portion  70 . Moreover, such an automated arrangement could be implemented with the device  10  of  FIGS. 1-4 . 
     In some implementations, the controller  50  is coupled with a sensor that detects skin properties. This information can be used to servo-control the actuator  28  to tailor the injection pressure, and, therefore, the depth of penetration of drug into the skin for a particular application. For instance, when the device  10  is used on a baby, the sensor detects the softness of the baby&#39;s skin, and the controller  50  uses the properties of the baby&#39;s skin and consequently reduces the injection pressure. The injection pressure can be adjusted, for example by controlling the current amplitude applied to the wires  30  and/or the current pulse rise time and/or duration. When used on an adult or someone with sun damaged skin, the controller may increase the injection pressure. The injection pressure may be adjusted depending on location of the skin on the body, for example, the face versus the arm of the patient. The injection pressure can also be tailored to deliver the drug just underneath the skin or deep into muscle tissue. Moreover, the injection pressure may be varied over time. For instance, in some implementations, a large injection pressure is initially used to pierce the skin with the drug, and then a lower injection pressure is used to deliver the drug. A larger injection may also be used to break a seal that seals the chamber or vial. 
     Skin is a non-linear, viscoelastic material. Microscopic changes in cellular mechanical properties or adhesion between tissue can be observed as macroscopic changes in static or dynamic mechanical tissue properties. These factors combine to determine the behavior of skin in response to outside stimulants. For small force perturbations about an applied static force, the skin mechanical dynamics can be approximated as a linear mechanical system relating the applied force F(t) to skin deformation x(t) as: 
                       F   ⁡     (   t   )       =       I   ⁢         ⅆ   2     ⁢     x   ⁡     (   t   )           ⅆ     t   2           +     B   ⁢       ⅆ     x   ⁡     (   t   )           ⅆ   t         +     Kx   ⁡     (   t   )           ,           (   1   )               
where I is the inertia in kg, B is the viscosity in kg/s, and K is the stiffness in N/m of skin. After taking the Laplace transform of equation (1), the equivalent transfer function representing the mechanical compliance of the skin as a function of frequency, ÿ, is:
 
     
       
         
           
             
               
                 
                   
                     
                       
                         x 
                         ⁡ 
                         
                           ( 
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                           ) 
                         
                       
                       
                         F 
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                   ⁢ 
                   where 
                 
               
               
                 
                   ( 
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                     G 
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                       K 
                     
                   
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                   3 
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                         B 
                         
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                   ( 
                   5 
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     A Bode plot (gain vs. freq.) can be obtained for the above mechanical system, illustrating a decrease in compliance with increase skin stiffness. A tailored stochastic sequence can also be performed by tuning F(t) to pull out the relevant parameters. As such, skin properties can be determined with system identification techniques, such as using Volterra series for system representation. Such techniques are described in the article “The Identification of Nonlinear Biological Systems: Volterra Kernel Approaches,” by Michael J. Korenberg and Ian W. Hunter, Annals of Biomedical Engineering, Vol. 24, pp. 250-269, 1996, the entire contents of which are incorporated herein by reference. 
     Referring now to  FIG. 13 , there is shown a skin property sensor  200  associated with the drug delivery device  10 . The sensor  200  includes an electromagnetically driven voice coil  202  coupled to a force transducer  206  with a flexure  204 . The force transducer  206  in turn is coupled to a linear variable differential transducer (LVDT)  208  with a sensor tip  201 . In the implementation shown, the voice coil  202 , the force transducer  206 , and the LVDT  208  are connected to a controller such as the controller  50 , which drives the sensor  200  as well as receives signals from the sensor  200 . The sensor  200  can be integrated with the device  10 , or it can be a separate unit. As shown, the sensor is positioned within the device  10 , with the sensor tip  201  located near the orifice  14  (see also  FIGS. 1A ,  5 A, and  6 A). 
     Accordingly, when the device  10  is used with the sensor  200 , the device  10  is initially placed against the skin, S, of the body such that the sensor tip  201  also rests against the skin. The controller  50  then drives the voice coil  202 , for example, up to 20 kHz, to perturb the skin, while the force transducer  202  detects the force the tip  201  applies to the skin, and the LVDT  208  detects the displacement of the skin. This data is fed back to the controller  50  which then evaluates the skin properties with the system identification techniques described earlier. Based on the detected skin properties, the controller  50  directs the actuator  28  to eject the drug, D, contained in the chamber  12 , through the orifice  14  with the desired injection pressure. Alternatively, a body portion  210  in which the chamber  12  is defined can function as the sensor tip  201 . In such implementations, the body portion  210  would be coupled to the LVDT  208  and force sensor  206  so that the chamber  12 , body portion  210 , and sensor  200  would be positioned in line. 
     Other skin property sensor arrangements can also be used with the device  10 , such as the sensor configuration  300  shown as a block diagram in  FIG. 14 . The sensor  300  includes a linear electromagnetic actuator  302  (e.g., model no. 4910, available from Bruel and Kjaer) vertically mounted to a rigid frame. A strain gauge type load cell  304  (e.g., model no. ELF-TC13-15, available from Entran, of Fairfield, N.J.) is mounted to the actuator platform for the purpose of measuring the DC offset of the system corresponding to the static loading, as measured with a multimeter  303  (e.g., model no. HP 972A, available from Hewlett Packard, or Palo Alto, Calif.) via a signal conditioning amplifier  305 . Below the load cell  304  is an impedance head  306  (Bruel and Kjaer model no. 8001) consisting of a piezoelectric accelerometer  306   a  and a piezoelectric force transducer  306   b . The two outputs from the accelerometer record the force applied to the skin and its resulting acceleration. Two charge amplifiers  308 ′,  308 ″ (generally  308 ) (Bruel and Kjaer model no. 2635) transform the force to a proportional voltage and doubly integrate the acceleration to give the skin displacement. The actuator  302  is driven by an algorithm, such as a Visual BASIC program, that simulates a Dynamic Signal Analyzer through a power amplifier  310 . The algorithm outputs a swept sinusoidal signal within a range of pre-determined frequencies. This modulation is a small perturbation on top of an initial static load, which is determined from the output voltage of the load cell  304 . The measured force and displacement of the actuator are then input to two separate channels of a data acquisition board  312  and used to calculate the compliance transfer function gain and phase with a computer or the controller  50 . In one implementation, there is a 50 kHz per channel of the data acquisition board, which can be increased to 100 kHz per channel when multiplexed. The A/D is 18 bits with ±4.5 V, while the D/A is 18 bits with ±3.0 V. Like that shown in  FIG. 13  for the sensor  200 , the sensor  300  is preferably associated with the device  10  through the controller  50 . Accordingly, properties of the skin are analyzed by the controller  50  based on the data from the sensor  300 . The controller  50  then directs the device  10  to eject drug into the body with the appropriate injection pressure. 
     Although the sensors  200  and  300  are shown in combination with the device  10 , the sensors can be combined with other types of medical devices. For example, the sensor can be combined with other types of needleless injectors such as those using magnetic, chemical, hydraulic, and spring actuators, and those described in U.S. application Ser. No. 10/200,574 filed Jul. 19, 2002, and U.S. Provisional Application No. 60/409,090 filed Sep. 6, 2002, incorporated by reference in their entireties. Additionally, the sensor can be combined with injectors that use needles, such as microneedle injectors, and those described in U.S. application Ser. Nos. 10/238,844 filed Sep. 9, 2002 and 10/278,049 filed Oct. 21, 2002, also incorporated by reference in their entireties. Advantageously, the sensed properties can be used to control the depth and/or insertion force of the needles. 
     Furthermore, the sensors  200 ,  300  can be used to measure skin properties of a subject, as described above, or they can be used, to measure properties of other body surfaces. For example, the sensor can be used to measure properties of the internal anatomy of subject, such as the surface of an internal cavity or organ during a surgical procedure. 
     In some embodiments, the sensors  200  and  300  can be configured as stand alone units. Thus, the system components discussed in relation to  FIGS. 13 and 14  can be packaged within a single housing. The housing can be tethered to an external power source, or can include an internal power source, such as a battery. Additionally, a stand alone unit can be configured as a wearable device that can attach to a patient&#39;s body using a bandage, or an adhesive. For example, a small force transducer and an accelerometer can be packaged in an adhesive bandage that is placed on the skin. The transducer first resonates at a resonant frequency (e.g., 50 Hz) for a period of time (e.g., several seconds). The transducer stimulates the local skin and the accelerometer detects the displacement of the skin. A controller can then record the resulting skin displacement in a memory and calculate the compliance gain of the skin. The controller can further determine the mechanical behavior of the skin (e.g., stiffness) using the calculated compliance gain. Still further, the controller can further identify the type of skin using its calculated mechanical behavior and/or compliance gain (e.g., that of a baby or of an adult). The sensor can ultimately generate a signal or command used as an indicator to an operator and/or a control signal to a medical device. 
     While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims. For example, contractile polymers, or any other suitable contracting material, can be used instead of the shape memory alloy. The device  10  may include multiple chambers or may accommodate multiple drug vials. Thus, the device  10  is able to deliver drug sequentially or simultaneously. For example, the device  10  is able to deliver two or more drugs at once to the body.