Patent Publication Number: US-10326347-B2

Title: Controlled needle-free transport

Description:
RELATED APPLICATIONS 
     This application is a Divisional of U.S. application Ser. No. 14/490,126 filed Sep. 18, 2014, which is a Continuation of U.S. application Ser. No. 13/708,303 filed Dec. 7, 2012, now U.S. Pat. No. 8,992,466, which is a Divisional of U.S. application Ser. No. 12/906,525, filed on Oct. 18, 2010, now U.S. Pat. No. 8,328,755, which is a Divisional of U.S. application Ser. No. 11/354,279, filed Feb. 13, 2006, now U.S. Pat. No. 7,833,189, which is a Continuation-in-Part of U.S. application Ser. No. 11/352,916 filed on Feb. 10, 2006, now abandoned, which claims the benefit of U.S. Provisional Application No. 60/652,483, filed on Feb. 11, 2005. The entire teachings of the above applications are incorporated herein by reference. 
    
    
     BACKGROUND 
     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 very 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 of. 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. Thus, it would be advantageous to be able to inject small, precise volumes of pharmaceuticals quickly through the skin without the potential of a needle breaking off in the animal. 
     SUMMARY OF THE INVENTION 
     Some have proposed using needle-free devices to effectively deliver drugs to a biological body. For example, in some of these proposed devices, pressurized gas is used to expel a drug from a chamber into the body. In another device, a cocked spring is released which then imparts a force on a chamber to expel the drug. In these types of devices, however, the pressure applied to the drug decreases as the gas expands or the spring extends. It is desirable, however, for the injection pressure to remain substantially the same or even increase during the injection period. Examples of needleless injection devices are described in U.S. Pat. No. 6,939,323, entitled “Needleless Injector” and U.S. application Ser. No. 10/657,734, filed on Sep. 8, 2003 and entitled “Needleless Drug Injection Device” both incorporated herein by reference in their entireties. 
     Other needle-free injection devices are either controllable in a very limited sense (e.g., gas discharge actuators or spring actuators) or are controllable in a feed-forward sense (e.g., shaped memory materials, such as a nickel-titanium alloy known as Nitinol)—an injection profile being determined a priori and fed forward to a pressure actuator prior to injection. 
     In accordance with aspects of the invention, a servo-controlled needle-free transfer device transfers a substance across a surface of a biological body. The device includes an actuator capable of generating a high-speed, high-pressure pulse that is both controllable and highly predictable. The device can be combined with a servo-controller receiving inputs from one or more sensors. Beneficially, the transfer device can adjust or tailor the pressure profile of a transfer in real-time. That is, the transfer device can adjust a pressure profile of the transfer during the course of the transfer responsive to a physical property also sensed during the course of the transfer. 
     The servo-controlled needle-free injector provides for the injection of a formulation into an animal that is dynamically controlled, or tailored in real-time according to requirements of a particular animal and/or other local environmental factors. Such control allows for a single injection device to deliver controlled injection of a formulation responsive to other conditions and requirements by adjusting injection pressure responsive to local thickness of the skin and/or other environmental factors, such as temperature. 
     In one aspect of the invention, a needle-free, transdermal transfer device includes a reservoir for storing the substance; a nozzle in fluid communication with the reservoir; and a controllable electromagnetic actuator in communication with the reservoir. The electromagnetic actuator includes a stationary magnet assembly providing a magnetic field and a coil assembly slidably disposed with respect to the magnet assembly. The coil assembly receives an electrical input and generates in response a force proportional to the received input. The force results from interaction of an electrical current, induced in the coil assembly by the electrical input, and the magnetic field. The force can be used for needle-free transfer of the substance between the reservoir and the biological body. Thus, a Lorentz force drive transfers a substance, such as fluid, across the surface of the body. The needle-free transfer is also variable, responsive to variations in the received input during the course of an actuation. 
     Needle-free drug injection apparatus and methods described herein use a specially-configured electromagnetic actuator in combination with one or more nozzles to effectively inject a drug through an animal&#39;s skin to a selected depth without first piercing the skin with a lance or needle. The same device can also be used to collect a sample from the animal. 
     The controllable electromagnetic actuator is bi-directional, being capable of generating a positive force responsive to a first electrical input and a negative force responsive to a second electrical input. The electromagnetic actuator forces the substance through a nozzle, producing a jet having sufficient velocity to pierce the surface of the biological body. For example, in some embodiments, the substance is expelled through the nozzle with an injection velocity of at least about 100 meters per second. The force and nozzle can also be controlled to produce an injection to a desired depth. The electrical input signal can be provided by a rechargeable power source. In some embodiments, the controllable electromagnetic actuator itself is adapted to recharge the rechargeable power source. 
     The device also includes a controller in electrical communication with the controllable electromagnetic actuator. The device may further include at least one sensor in electrical communication with the controller, the sensor sensing a physical property and the controller generating the electrical input responsive to the sensed physical property. For example, the sensed property may be one or more of position, force, pressure, current, and voltage. The controller may include a processor that contributes to the generation of an electrical input. The device optionally includes an analyzer adapted to analyze a sample collected from the body. The controller can be adapted to provide an electrical input responsive to the analyzed sample. 
     In some embodiments, a remote communications interface is also provided in electrical communication with the controller. In this configuration, the controller can generate the electrical input responsive to a communication received through the remote communications interface. 
     The device can be configured as a multi-shot device capable of providing several independent needle-free transfers. Beneficially, these needle-free transfers may occur in rapid succession. This configuration supports treatment of a substantial surface area by administering multiple transfers that are spaced apart across the surface. 
     The electromagnetic actuator may include a magnet assembly providing a magnetic field. The magnet assembly is generally fixed in position relative to the nozzle. The actuator also includes an electrically conducting coil assembly of at least one turn carrying an electrical current related to the electrical input. The coil assembly is slidably disposed with respect to the magnet assembly. A current produced within the coil assembly interacts with the magnetic field to produce a force responsive to the direction and magnitudes of the electrical current and the magnetic field. Preferably, the magnetic field is radially directed with respect to the coil. 
     The mechanical force is applied to a reservoir coupled at one end to a nozzle, producing a pressure within the reservoir. The magnitude of the pressure varies according to the mechanical force and causes transfer of a substance across the surface of the biological body between the biological body and the reservoir. Beneficially, the applied force can be bi-directional, producing with the same actuator a positive pressure and a negative pressure or vacuum. Additionally, the applied mechanical force can be varied during the course of an actuation cycle by varying the electrical input. 
     In some embodiments, the rise-time associated with producing the generated force is about 5 milliseconds or less. The resulting force and stroke provided by the actuator are sufficient in magnitude and duration to transfer a volume of up to at least about 300 micro liters of substance. The compact size and power requirements of the actuator support a portable, hand-held unit including a reservoir, nozzle, power source, and the controllable electrical actuator. 
     A method of treating a disease using the device includes first piercing a surface of a biological body with a needle-free transdermal transport device. The needle-free device then collects a sample from the biological body by creating a vacuum within the reservoir to suck a sample or bolus from the body into the reservoir. A dosage of an active compound is next determined responsive to the collected sample. The needle-free device injects the determined dosage of active compound into the biological body. For example, a sample of blood is extracted from a patient. The sample is analyzed to determine a blood sugar level. The determined value is then used to calculate a dosage of insulin for the patient, the dosage being administered by controlling the electrical input to the device. 
     Collecting a sample may include injecting a first substance, such as a saline solution. A sample is then collected and re-injected using the same needle-free device. The sample re-injection process can be repeated multiple times to achieve a suitable bolus of interstitial fluid from the body. 
     In another aspect of the invention, a linear electromagnetic actuator includes a stationary magnet assembly providing a magnetic field and a coil receiving an electrical input. The coil is slidably disposed with respect to the magnet assembly. The device also includes a bearing that is slidably engaged with at least a portion of the coil. Linear movement of the coil responsive to a force generated by interaction of the electrical input within the coil and the magnetic field is facilitated by the bearing. 
     Although the invention is described herein in the context of needle-free transfers, one or more of the concepts described herein can also be combined with a needle to accomplish transfer of a substance across the surface of a body, the surface being pierced first by the needle. 
    
    
     
       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. 1  is a schematic block diagram of one embodiment of a controllable, needle-free transdermal transfer device; 
         FIGS. 2A and 2B  are cross-sectional diagrams of one embodiment of a controllable electromagnetic actuator usable with the device of  FIG. 1 , respectively shown in an extended and retracted configuration; 
         FIG. 3A  is a graph depicting a current-versus-time profile of an exemplary electrical input to the controllable electromagnetic actuator of  FIG. 2A ; 
         FIG. 3B  is a graph depicting a pressure-versus-time profile of an exemplary pressure generated within a reservoir used in the transfer of a substance, the pressure being generated by the controllable electromagnetic actuator responsive to the electrical input of  FIG. 3A ; 
         FIG. 4  is a partial cut-away perspective diagram of an embodiment of a controllable needle-free transdermal transfer device; 
         FIG. 5  is a partial cut-away perspective diagram of an alternative embodiment of a controllable needle-free transdermal transfer device; 
         FIG. 6  is a more detailed partial cut-away perspective diagram of the controllable electromagnetic actuator provided in the device of  FIG. 5  coupled to a syringe; 
         FIG. 7  is a rear perspective diagram of an embodiment of the controllable electromagnetic actuator provided in the device of  FIG. 5  coupled to a syringe; 
         FIGS. 8A and 8B  are schematic block diagrams of a needle-free transdermal transport device providing a sampling and analysis capability, respectively shown in the sampling and injection configurations; 
         FIG. 9A  is a flow diagram depicting an embodiment of a needle-free sample, analyze, and inject process; 
         FIG. 9B  is a more detailed flow diagram depicting an embodiment of an exemplary needle-free collection process; 
         FIGS. 10A and 10B  are graphs depicting current versus time profile of exemplary electrical inputs to the controllable electromagnetic actuator of  FIG. 2A, 4, 5 , or  8 A and  8 B for single and multi-sample operation, respectively; 
         FIG. 11  is an alternative embodiment of a needle-free transdermal transfer device also providing sample and injection capabilities; 
         FIG. 12  is a perspective diagram showing surface treatment using a multi-shot needle-free transdermal transport device; 
         FIG. 13  is a graph depicting current-versus-time profile of exemplary electrical inputs to the controllable electromagnetic actuators of  FIG. 2A, 4, 5, 8A or 8B  for multi-shot transfers; 
         FIGS. 14A and 14B  are front and rear perspective diagrams of an exemplary portable needle-free transdermal transport device; 
         FIG. 15  is a schematic block diagram of a mechanical recharging unit coupled to a rechargeable needle-free transdermal transport device for recharging an internal power source; 
         FIG. 16  is a schematic block diagram of an automated needle-free transdermal transport system adapted to automatically administer a needle-free transfer to an animal; 
         FIG. 17  is a schematic diagram of a needle-free transdermal transport device injecting a substance into an animal&#39;s joint; and 
         FIG. 18  is a schematic block diagram of an alternative needle-free transdermal transport device including a bellows reservoir. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     A description of preferred embodiments of the invention follows. 
     A needle-free transdermal transport device, or injection device, is configured to inject a substance beneath the skin of an animal body. Injection devices include devices having one or more needles configured to pierce the skin prior to injection of the substance (e.g., typical hypodermic needle). Other injection devices are configured to inject a substance beneath the skin without first piercing the skin with a needle (i.e., needle-free). It should be noted that the term “needle-free” as used herein refers to devices that inject without first piercing the skin with a needle or lance. Thus, needle-free devices may include a needle, but the needle is not used to first pierce the skin. Some needle-free injection devices rely on a pioneer projectile ejected from the device to first pierce the skin. Other needle-free injection devices rely on pressure provided by the drug itself. 
     Referring to  FIG. 1 , there is shown a schematic block diagram of an exemplary needle-free transdermal transport device  100  used to transfer a substance across the surface  155  of a biological body  150 . For example, the device  100  can be 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. Alternatively or in addition, the same device  100  can be used to collect a sample from a biological body  150  by withdrawing the collected sample through the surface  155  of the body and into an external reservoir  113  that may be provided within the device  100 . 
     The device  100  typically includes a nozzle  114  to convey the substance through the surface  155  of the biological body at the required speed and diameter to penetrate the surface  155  (e.g., skin) as required. Namely, substance ejected from the nozzle  114  forms a jet, the force of the jet determining the depth of penetration. The nozzle  114  generally contains a flat surface, such as the head  115  that can be placed against the skin and an orifice  101 . It is the inner diameter of the orifice  101  that controls the diameter of the transferred stream. Additionally, the length of an aperture, or tube  103 , defining the orifice  101  also controls the transfer (e.g., injection) pressure. 
     Preferably, the biological surface  155  is stretched prior to transfer of the substance. First stretching the surface or skin permits the skin to be pierced using a lower force than would otherwise be required. An analogy would be comparing a flaccid balloon to a taught balloon. The flaccid balloon would generally much more difficult to pierce. 
     Stretching may be accomplished by simply pressing the nozzle  114  into the surface  155  of the skin. In some embodiments, a separate surface reference or force transducer is included to determine when the surface  155  has been sufficiently stretched prior to transfer. Such a sensor can also be coupled to a controller, prohibiting transfer until the preferred surface properties are achieved. 
     In some embodiments, a standard hypodermic needle is cut to a predetermined length and coupled to the head  115 . One end of the needle is flush, or slightly recessed, with respect to the surface of the head  115  that contacts the skin to avoid puncturing the skin during use. The internal diameter of the needle (e.g., 100 μm) 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  115  to reduce assembly steps. In general, the length of the orifice is selectable, for example ranging from 500 μm to 5 mm, while its diameter can range from 50 μm to 200 μm. In one particular embodiment, the diameter of the orifice is about 120 μm. 
     The nozzle  114  can be coupled to a syringe  112  defining a reservoir  113  for temporarily storing the transferred substance. The syringe  112  also includes a plunger or piston  126  having at least a distal end slidably disposed within the reservoir  113 . Movement of the plunger  126  along the longitudinal axis of the syringe  112  in either direction creates a corresponding pressure within the reservoir  113 . In some embodiments, the syringe  112  is integral to the device  100 . In other embodiments, the syringe  112  is separately attachable to the device  100 . For example, a commercially-available needle-free syringe  112  can be attached to the device  100 , such as a model reference no. 100100 syringe  112  available from Equidine Systems Inc. of San Diego, Calif. 
     The nozzle  114  can be releasably coupled to the syringe  112  or the distal end of the device  100 , such that different nozzles can be used for injecting and sampling (i.e., sucking), each different nozzle tailored for its intended use. Thus, a sampling nozzle may include a larger orifice  101 , tapering into the lumen  103  thereby promoting a more efficient collection, or greater capacity sample. 
     Beneficially, a pressure is selectively applied to the chamber  113  using a controllable actuator. A specially-designed electromagnetic actuator  125  is configured to generate a high-pressure pulse having a rapid rise time (e.g., less than 1 millisecond). The actuator  125  can be used in needle-free injection devices that rely on high-pressure actuators to inject a formulation beneath the skin. Beneficially, the actuator is dynamically controllable, allowing for adjustments to the pressure-versus-time during actuation. At least one advantage of the electromagnetic actuator over other needle-free devices is its relatively quiet operation. Actuation involves movement of a freely suspended coil within a gap, rather than the sudden release of a spring or the discharge of a gas. Actuation of the freely-moving coil in the manner described herein results in quiet operation, which is an important feature as it contributes to reducing pain and anxiety during administration to the recipient and to others that may be nearby. 
     In more detail, the electromagnetic actuator  125  is configured to provide a linear force applied to the plunger  126  to achieve transdermal transfer of the substance. Transfer of the force can be accomplished with a force-transfer member  110 , such as a rigid rod slidably coupled through a bearing  111 . The rod may be secured at either end such that movement of the actuator in either direction also moves the plunger  126 . The bearing restricts radial movement of the rod  110 , while allowing axial movement. 
     In some embodiments, the actuator  125  includes a stationary component, such as a magnet assembly  105 , and a moveable component, such as coil assembly  104 . A force produced within the coil assembly  104  can be applied to the plunger  126  either directly, or indirectly through the rod  110  to achieve transdermal transfer of the substance. Generally, the actuator  125 , bearing  111  and syringe  112  are coupled to a frame or housing  102  that provides support and maintains fixed position of these elements during an actuation. 
     In some embodiments, the device  100  includes a user interface  120  that provides a status of the device. The user interface may provide a simple indication that the device is ready for an actuation. For example, a light emitting diode (LED) coupled to a controller  108  can be enabled when sufficient conditions are satisfied for an injection. More elaborate user interfaces  120  can be included to provide more detailed information, including a liquid crystal display (LCD), cathode ray tube (CRD), charge-coupled device (CCD), or any other suitable technology capable of conveying detailed information between a user and the device  100 . Thus, user interface  120  may also contain provisions, such as a touch screen to enable an operator to provide inputs as user selections for one or more parameters. Thus, a user may identify parameters related to dose, sample, parameters related to the biological body, such as age, weight, etc. 
     A power source  106  provides an electrical input to the coil assembly  104  of the actuator  125 . As will be described in more detail below, an electrical current applied to the coil assembly  104  in the presence of a magnetic field provided by the magnet assembly  105  will result in a generation of a mechanical force capable of moving the coil assembly  104  and exerting work on the plunger  126  of the syringe  112 . The electromagnetic actuator is an efficient force transducer supporting its portability. An exemplary device described in more detail below expends about 50 Joules of energy to deliver about 200 micro-liters of a fluid. For comparison, a standard 9-volt batter can provide up to about 8,500 Joules. 
     A controller  108  is electrically coupled between the power source  106  and the actuator  125 , such that the controller  108  can selectively apply, withdraw and otherwise adjust the electrical input signal provided by the power source  106  to the actuator  125 . The controller  108  can be a simple switch that is operable by a local interface. For example, a button provided on the housing  102  may be manipulated by a user, selectively applying and removing an electrical input from the power source  106  to the actuator  125 . In some embodiments, the controller  108  includes control elements, such as electrical circuits, that are adapted to selectively apply electrical power from the power source  106  to the actuator  125 , the electrical input being shaped by the selected application. Thus, for embodiments in which the power source  106  is a simple battery providing a substantially constant or direct current (D.C.) value, can be shaped by the controller to provide a different or even time varying electrical value. In some embodiments, the controller  108  includes an on-board microprocessor, or alternatively an interconnected processor or personal computer providing multifunction capabilities. 
     In some embodiments, the needle-free transdermal transport device  100  includes a remote interface  118 . The remote interface  118  can be used to transmit information, such as the status of the device  100  or of a substance contained therein to a remote source, such as a hospital computer or a drug manufacturer&#39;s database. Alternatively or in addition, the remote interface  118  is in electrical communication with the controller  108  and can be used to forward inputs received from a remote source to the controller  108  to affect control of the actuator  125 . 
     The remote interface  118  can include a network interface, such as a local area network interface (e.g., Ethernet). Thus, using a network interface card, the device  100  can be remotely accessed by another device or user, using a personal computer also connected to the local area network. Alternatively or in addition, the remote interface  118  may include a wide-area network interface. Thus, the device  100  can be remotely accessed by another device or user over a wide-area network, such as the World-Wide Web. In some embodiments, the remote interface  118  includes a modem capable of interfacing with a remote device/user over a public-switched telephone network. In yet other embodiments, the remote interface  118  includes a wireless interface to access a remote device/user wirelessly. The wireless interface  118  may use a standard wireless interface, such as Wi-Fi standards for wireless local area networks (WLAN) based on the IEEE 802.11 specifications; new standards beyond the 802.11 specifications, such as 802.16(WiMAX); and other wireless interfaces that include a set of high-level communication protocols such as ZigBee, designed to use small, low power digital radios based on the IEEE 802.15.4 standard for wireless personal area networks (WPANs). 
     In some embodiments the controller receives inputs from one or more sensors adapted to sense a respective physical property. For example, the device  100  includes a transducer, such as a position sensor  116 B used to indicate location of an object&#39;s coordinates (e.g., the coil&#39;s position) with respect to a selected reference. Similarly, a displacement may be used to indicate movement from one position to another for a specific distance. Beneficially, the sensed parameter can be used as an indication of the plunger&#39;s position as an indication of dose. In some embodiments, a proximity sensor may also be used to indicate a portion of the device, such as the coil, has reached a critical distance. This may be accomplished by sensing the position of the plunger  126 , the force-transfer member  110 , or the coil assembly  104  of the electromagnetic actuator  125 . For example, an optical sensor such as an optical encoder can be used to count turns of the coil to determine the coil&#39;s position. Other types of sensors suitable for measuring position or displacement include inductive transducers, resistive sliding-contact transducers, photodiodes, and linear-variable-displacement-transformers (LVDT). 
     Other sensors, such as a force transducer  116 A can be used to sense the force applied to the plunger  126  by the actuator  125 . As shown, a force transducer  116 A can be positioned between the distal end of the coil assembly and the force transfer member  110 , the transducer  116 A sensing force applied by the actuator  125  onto the force-transfer member  110 . As this member  110  is rigid, the force is directly transferred to the plunger  126 . The force tends to move the plunger  126  resulting in the generation of a corresponding pressure within the reservoir  113 . A positive force pushing the plunger  126  into the reservoir  113  creates a positive pressure tending to force a substance within the reservoir  113  out through the nozzle  114 . A negative force pulling the plunger  126  proximally away from the nozzle  114  creates a negative pressure or vacuum tending to suck a substance from outside the device through the nozzle  114  into the reservoir  113 . The substance may also be obtained from an ampoule, the negative pressure being used to pre-fill the reservoir  113  with the substance. Alternatively or in addition, the substance may come from the biological body representing a sampling of blood, tissue, and or other interstitial fluids. In some embodiments, a pressure transducer (not shown) can also be provided to directly sense the pressure applied to a substance within the chamber. 
     An electrical sensor  116 C may also be provided to sense an electrical input provided to the actuator  125 . The electrical may sense one or more of coil voltage and coil current. The sensors  116 A,  116 B,  116 C (generally  116 ) are coupled to the controller  108  providing the controller  108  with the sensed properties. The controller  108  may use one or more of the sensed properties to control application of an electrical input from the power source  106  to the actuator  125 , thereby controlling pressure generated within the syringe  112  to produce a desired transfer performance. For example, a position sensor can be used to servo-control the actuator  125  to pre-position the coil assembly  104  at a desired location and to stabilize the coil  104  once positioned, and conclude an actuation cycle. Thus, movement of the coil assembly  104  from a first position to a second position corresponds to transfer of a corresponding volume of substance. The controller can include a processor programmed to calculate the volume based on position give the physical size of the reservoir. 
     An actuation cycle described in more detail below, generally correspond to initiation of an electrical input to the actuator  125  to induce transfer of a substance and conclusion of the electrical input to halt transfer of the substance. A servo-control capability combined with the dynamically controllable electromagnetic actuator  125  enables adjustment of the pressure during the course of an actuation cycle. One or more of the sensors  116  can be used to further control the actuation cycle during the course of the transfer, or cycle. Alternatively or in addition, one or more of local and remote interfaces can also be used to further affect control of the actuation cycle. 
     In some implementations, the controller  108  is coupled with one more other sensors (not shown) that detect respective physical properties of the biological surface. This information can be used to servo-control the actuator  125  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  100  is used on a baby, the sensor detects the softness of the baby&#39;s skin, and the controller  108  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 electrical input signal applied to the actuator  125  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. 
     In more detail, the power source  106  can be external to the device  100 . For example, the device  100  can be coupled to a separate electrical power supply. Preferably, however, the power source  106  is self-contained within the device  100  to promote portability of the device  100 . Such portability is particularly beneficial in field applications, such as treating livestock or administrating of medicines, such as vaccines to people or animals in remote areas. 
     The power source  106  can include a replaceable battery, such as a ubiquitous 9-volt dry cell battery. Alternatively, the power source  106  includes a rechargeable device, such as a rechargeable battery (e.g., gel batteries; lead-acid batteries; Nickel-cadmium batteries; Nickel metal hydride batteries; Lithium ion batteries; and Lithium polymer batteries). In some embodiments, the power source  106  includes a storage capacitor. For example, a bank of capacitors can be charged through another power source, such as an external electrical power source. 
     In more detail, the electromagnetic actuator  125  includes a conducting coil assembly  104  disposed relative to a magnetic field, such that an electrical current induced within the coil results in the generation of a corresponding mechanical force. The configuration is similar, at least in principle, to that found in a voice coil assembly of a loud speaker. Namely, the relationship between the magnetic field, the electrical current and the resulting force is well defined and generally referred to as the Lorentz force law. 
     Preferably, the coil  104  is positioned relative to a magnetic field, such that the magnetic field is directed substantially perpendicular to the direction of one or more turns of the coil  104 . Thus, a current induced within the coil  104  in the presence of the magnetic field results in the generation of a proportional force directed perpendicular to both the magnetic field and the coil (a relationship referred to as the “right hand rule”). 
     In more detail a cross-sectional diagram of an electromagnetic impulse actuator  200  is shown in  FIG. 2A . The device  200  includes a magnet assembly  205  defining an annular slotted cavity  214  and a coil assembly  203  slidably disposed therein. The stroke of the coil  212  can be controlled by the lengths of the coil and magnet assembly. Thus, the electromagnetic actuator can be configured to transfer a substantial volume of a substance during a single, sustained stroke. For example, a volume of up to 300 micro-liters or more may be transferred with a single stroke. Alternatively or in addition, the entire contents of a vial or syringe may be transferred in multiple smaller doses. For example, substantially the entire contents of a 300 micro-liter vial may be transferred to an animal in ten separate injections of 30 micro-liters each. 
     The controllability of the actuator also allows for a precise transfer. For example, a substance may be delivered to a biological body with minimum volumetric increments of about 1%. Thus, for a 200 micro-liter volume, the dosage may be tailored in 200 nano-liter steps. Thus, a single syringe loaded with a sufficient volume can deliver various doses by controlling the electrical input to the coil. Operation of such an actuator is deterministic further lending itself to precision control. 
     The magnet assembly  205  includes a column of magnets  204 A,  204 B disposed along a central axis. The column of magnets can be created by stacking one or more magnetic devices. For example, the magnetic devices can be permanent magnets. As a greater magnetic field will produce a greater mechanical force in the same coil, thus stronger magnets are preferred. As portability and ease of manipulation are important features for a hand-held device  100 , high-density magnets are preferred. 
     One such category of magnets are referred to as rare-earth magnets, also know as Neodymium-Iron-Boron magnets (e.g., Nd 2 Fe 14 B). Magnets in this family are very strong in comparison to their mass. Currently available devices are graded in strength from about N24 to about N54—the number after the N representing the magnetic energy product, in megagauss-oersteds (MGOe). In one particular embodiment, N50 magnets are used. The magnetic field produced by the magnets generally follows field lines  208 , with rotational symmetry about the central axis for the configuration shown. 
     The magnets  204 A,  204 B are attached at one end of a right-circular cylindrical shell  201  defining a hollowed axial cavity and closed at one end. An annular slot remains being formed between the magnets  204 A,  204 B and the interior walls of the case and accessible from the other end of the shell  201 . An exemplary shell  201  is formed with an outside diameter of about 40 mm and an inside diameter of about 31.6 mm, resulting in a wall thickness of about 4.2 mm. In this embodiment, the magnets  204 A,  204 B are cylindrical, having a diameter of about 25.4 mm. 
     The shell  201  is preferably formed from a material adapted to promote containment therein of the magnetic fields produced by the magnets  204 A,  204 B. For example, the shell  201  can be formed from a ferromagnetic material or a ferrite. One such ferromagnetic material includes an alloy referred to as carbon steel (e.g., American Iron and Steel Institute (AISI) 1026 carbon steel). An end cap  206  is also provided of similar ferromagnetic material being attached to the other end of the magnets  204 A,  204 B. Placement of the end cap  206  acts to contain the magnetic field therein and promoting a radially-directed magnetic field between the annular gap formed between the end cap  206  and the outer walls of the shell  201 . The end cap is generally thicker than the shell walls to promote containment of the magnetic fields as they loop into the end of the top magnet  204 A. For the exemplary shell  201  embodiment described above, the end cap  206  has an axial thickness of about 8 mm. 
     The coil assembly  203  includes a coil  212  formed from a conducting material, such as copper wire wound about a bobbin  210 . The bobbin  210  can be cylindrical and defines an axial cavity sized to fit together with the coil  212  within the annular cavity  214 . In some embodiments, the bobbin  210  is substantially closed at the end juxtaposed to the annular cavity  214 . The closed end forms a force-bearing surface adapted to push against a plunger  126  ( FIG. 1 ) or force-bearing rod  110  ( FIG. 1 ). 
     A strong, yet light-weight coil assembly  203  is preferred for applications requiring a rapid generation of substantial force, such as needle-free transfers. Preferably, the bobbin is formed from a strong, yet light-weight material such as aluminum or epoxy-loaded fiberglass. One such family of glass reinforced epoxy is sold under the trade name GAROLITE®. Suitable material selected from this family includes G10/FR4 material offering extremely high mechanical strength, good dielectric loss properties, and good electric strength properties, both wet and dry. Other materials include an all-polymeric reinforced, dull gold colored polytetrafluoroethylene (PTFE) compound that operates exceptionally well against soft mating surfaces such as 316 stainless steel, aluminum, mild steel, brass and other plastics available from Professional Plastics of Fullerton Calif. under the trade name RULON®. The bobbin  210  is thin-walled to fit within the annular slot. The bobbin  210  should also present a low coefficient of friction to those surfaces that may come in contact with either the shell  201 , the magnets  204 A,  204 B or the end cap  206 . In some embodiments, a low-friction coating can be applied to the bobbin. Such coatings include fluorocarbons, such as PTFE. 
     Generally, a non-conducting material such as epoxy-loaded fiberglass is preferred over a conducting material such as aluminum. Eddy currents created in the conducting material as it moves through the magnetic field tend to create a mechanical force opposing motion of the bobbin. Such an opposing force would counteract intentional movement of the coil thereby resulting in an inefficiency. Dielectric materials reduce or eliminate the production of such eddy currents. 
     A thin-walled bobbin  210  allows for a narrower annular slot  214  thereby promoting a greater magnetic field intensity across the gap. A substantial current flowing within the coil  212  can result in the generation of a substantial thermal load that could result in structural damage (e.g., melting). Other light-weight materials include machinable poly-acetals, which are particularly well suited to high-temperature applications. 
     Continuing with the exemplary embodiment, the bobbin  210  has an outside diameter of about 27 mm, an internal diameter of about 26 mm, and an axial length of about 46 mm. The coil  212  consists of six layers of 28 gauge copper wire wound onto the bobbin  210  at a rate of about 115 windings per coil length (about 35 mm) resulting in about 700 turns total. Using the N50 magnets with the 1026 carbon steel, the end cap  206  contains between about 0.63 and 0.55 Tesla (the value reducing outwardly along a radius measured from the center of the end cap  206 ). 
     Thus, a current flowing through the coil  212  is positioned at right angles to the magnetic field  208  produced between the end cap  206  and the shell  201  wall. This results in the generation of a force on the coil directed along the longitudinal axis, the direction of the force depending upon the directional flow of the current. For the above exemplary device, an electrical input, or drive voltage of about 100 volts applied across the coil for a duration of about 1 millisecond representing the pierce phase of an actuation cycle. A lesser electrical input of about −2 volts is applied for the transfer phase. The polarity of the applied input suggests that the transfer phase is a sample phase collecting a sample from the biological body. 
     Generally, the coil  212  receives the electrical input signal through two electrical leads  216 . The shell  201  includes one or more apertures  218  through which the leads  216  are routed to the power source  106  ( FIG. 1 ). The closed end of the shell  201  may contain one or more additional apertures through which air may be transferred during movement of the coil. Without such apertures and given the relative tight tolerances of the gap between the coil  212  and the annular slot  214 , a pressure would build up to oppose movement of the coil. Alternatively or in addition, the bobbin  210  may also have one or more apertures  220  to further inhibit the build up of damping pressures during actuation. 
       FIG. 2A  shows the coil assembly  203  after or during an injection phase in which the coil is forced out of the shell  201  thereby advancing the front plate.  FIG. 2B  shows the coil assembly  203  retracted within the shell  201  after a sampling phase in which the coil assembly  203  is drawn into the shell  201 . 
     In some embodiments, the conductive coil is configured to carry a relatively high-amplitude electrical current to produce a substantial force resulting in the generation of a substantial pressure. The coil also provides a relatively low inductance to support high-frequency operation thereby enabling rapid rise time (i.e., impulse) response. In some embodiments, the coil provides an inductance of less than 100 millihenries. Preferably, the coil inductance is less than about 50 millihenries. More preferably, the coil inductance is less than about 10 millihenries. For example, the coil inductance can be between about 5 and 10 millihenries. One way of providing the high-current capacity with the low inductance is using a coil formed by a large-diameter conductor that is configured with a low number of turns (e.g., 1 to 3 turns). 
     The result is a pressure actuator capable of generating a high-pressure pulse with a rapid rise time. Additionally, operation of the actuator is both controllable and highly predictable given the physical properties of the actuator and the input electrical current. Still further, the actuator is reversible providing forces in opposing directions based on the direction of current flow within the coil. 
     Additionally, the controllability allows for a tailored injection profile that can include a rapid high-pressure pulse to breach the outer layers of skin, followed by a lower-pressure, prolonged pulse to deliver the formulation. Referring to  FIG. 3A , an exemplary time varying electrical input is shown. The curve represents variation in an electrical current applied to the coil assembly  104  of the actuator  125 . At a first instant of time t 0  an electrical current is applied to the coil  104 . The current rises from a rest value (e.g., zero amps) to a maximum value I P  remaining at this maximum for a selectable duration and then transitioning to a different current value I T  at a later time t 1 . The current amplitude may remain substantially at this value, or continue to vary with time until a later time t 2 , at which the current returns to a rest value. 
     The entire period of time defined between times t 2  and t 0  can be referred to as an actuation period, or actuation cycle. For a current input having a shape similar to that just described, the period defined between times t 1  and t 0  can be referred to as a piercing phase. As the name suggests, the high current value I P  induces a corresponding high pressure that can be used to pierce the surface of a biological body without using a needle or lance. The remainder of the actuation cycle defined between times t 2  and t 1  can be referred to as a transfer phase. As this name suggests, the relatively lower current value I T  induces a lesser pressure that can be used to transfer a substance from the reservoir  113  ( FIG. 1 ) to the biological body through the perforation in the surface created during the piercing phase. 
     An exemplary plot of a pressure induced within the reservoir  113  ( FIG. 1 ) in response to the electrical input is illustrated in  FIG. 3B . As shown, the pressure rises from an initial rest value to a relative maximum value, P P , at a time t 0 , perhaps with a slight delay Δ resulting from the transfer characteristics of the electrical coil. This pressure value can be used to create a jet as described above in relation to  FIG. 1 . As the current is reduced during the transfer phase, the pressure similarly reduces to a lesser value P T  determined to achieve a desired transfer of the substance. The transfer phase continues until a desired volume of the substance is transferred, then the pressure is removed concluding the actuation cycle. 
     A servo-controlled injector includes a specially-designed electromagnetic pressure actuator configured in combination with a servo controller to generate an injection pressure responsive in real-time to one or more physical properties (e.g., pressure, position, volume, etc.). In some embodiments, the servo-controlled injector is a needle-free device. The electromagnetic pressure actuator generates a high-pressure pulse having a rapid rise time (e.g., less than 1 millisecond) for injecting a formulation beneath the skin. With such a rapid rise time, an entire transfer can be completed in less than about 10 milliseconds. The pressure provided by the actuator can be varied during the actuation of a single injection to achieve a desired result. For example, a first high-pressure is initially provided to the formulation to penetrate the outer surface layer of an animal&#39;s skin. Once the skin is penetrated, the pressure is reduced to a second, lower pressure for the remainder of the injection. The servo-controller can be used to determine when the skin is penetrated by sensing a change in pressure within the chamber and to adjust the injection pressure accordingly. 
     A servo-controller  108  receives input signals from the one or more sensors  116  and generates an output signal according to a predetermined relationship. The servo-controller output can be used to control the pressure by controlling the amplitude of electrical current driving the controllable actuator. 
     Real-time control can be accomplished by the servo controller  108  repeatedly receiving inputs from the sensors  116 , processing the inputs according to the predetermined relationship and generating corresponding outputs. In order to adjust the injection pressure during the course of an injection, the entire sense-control process must be performed numerous times during the period of the injection. For example, a servo-controller  108  can include a high-speed microprocessor capable of processing signals received from the sensors and rapidly providing corresponding output signals at a rate of 100 kHz (i.e., every 10 microseconds). Such rapid response times provide hundreds of opportunities to adjust pressure during the course of a single 5 to 10 millisecond injection. 
     As friction or drag on the coil assembly  104  represents an inefficiency, the coil can be floating within a cavity of the magnet assembly  105 . That is, there is the coil assembly  104  floats within a gap and is allowed to move freely. With no current applied to the coil assembly  104 , it would be allowed to slide back and forth with movement of the device  100 . Such movement may be undesirable as it may result in unintentional spillage of a substance form the reservoir or introduction of a substance, such as air, into the reservoir. Using a servo-controller with the position sensor  116 B, the position of the coil  104  can be adjusted such that the coil  104  is held in place in the presence of external forces (e.g., gravity) by the application of equal and opposite forces induced from the electrical input signal applied to the coil assembly  104 . 
     Alternatively or in addition, the actuator can be coupled to a bellows forming a chamber containing a formulation. For either configuration, actuation results in the generation of a pressure within the chamber, the chamber forcing the formulation through a nozzle. 
     An exemplary embodiment of a dynamically-controllable needle-free injection device  400  is shown in  FIG. 4 . The device  400  includes a controllable electromagnetic actuator  402  abutting one end to a pusher rod  406 . The axis of the pusher rod  406  is collinear with the longitudinal axis of the actuator  402  and slides through a bearing  408  to inhibit radial movement. A mounting adapter  412  is provided at a distal end of the device  400  for mounting a syringe  410 . A plunger of the syringe (not shown) resides within the mounting adapter  412  abutting the other end of the pusher rod  406 . A power source, such as a rechargeable capacitor  412  is disposed proximal to the actuator  402  for inducing currents within the actuator  402 . The device  400  also includes a button to initiate an injection and a controller  416  to control application of the power source to the actuator  402 . A housing, such as an elongated molded plastic case  418  is also provided to secure the different components with respect to each other. 
     An exemplary embodiment of a smaller, dynamically-controllable needle-free injection device  500  is shown in  FIG. 5 . The device  500  includes a compact electromagnetic actuator  502  having a distal force plate  504  adapted to abut a proximal end of a plunger  506  of a syringe  508 . The device  500  also includes a mounting member  512  to which a proximal end of the syringe  508  is coupled. A power source  514  is also disposed proximal to the actuator  502 , the different components being secured with respect to each other within a housing  516 . In some embodiments, a coupler  525  is provided to removably fasten the plunger  528  to the coil assembly  505 . This ensures that the plunger is moved in either direction responsive to movement of the coil assembly  505 . 
     Referring to  FIG. 6 , in more detail, the compact controllable electromagnetic actuator  502  includes a ferromagnetic shell  522  including a central magnetic core  520  capped by a ferromagnetic end cap  506 . A coil assembly  505  is slidably disposed within an annular slot of the magnet assembly floating freely within the slot. The distal end of the shell  522  includes one or more extensions  524  that continue proximally from the distal end of the shell  522  and terminating at the distal mounting plate  512 . In contrast to the devices of  FIGS. 1 and 4 , however, the device  502  does not include a separate bearing  111 ,  408 . Rather, the interior surface of the shell  522  including its extensions  524  provides a bearing for the coil assembly  505  allowing axial movement while inhibiting radial movement. A first bearing surface  550  is defined along a distal end of the coil assembly. The first bearing surface  550  slides against the interior surface of the extensions  524  during actuation. In some embodiments, a second bearing surface  555  is provided at a proximal portion of the coil assembly  505 . The second bearing surface  555  slides against the interior surface of the shell  522  during actuation. 
     The extensions  524  may include openings between adjacent extensions  524  as shown to reduce weight and to promote the flow of air to promote coil movement and for cooling. This configuration  502  rigidly couples the distal mounting plate  512  to the shell  522 , thereby increasing rigidity of the actuator  502  and reducing if not substantially eliminating any stress/strain loading on the housing  516  ( FIG. 5 ) caused by actuation of the device. 
     A rear perspective view of an exemplary compact Lorentz-force actuator  602  is shown in  FIG. 7 . The device  602  includes a magnet assembly having an external shell  622 . A coil assembly  605  is slidably disposed within the shell  622 , and adapted for axial translation. Multiple longitudinal extensions  624  are disposed about the axis and adapted to couple the shell  622  a mounting plate  612 . Openings are provided between adjacent extensions  624 . A syringe  608  is coupled to the mounting plate  612  at the distal end of the device  602 . One or more guides  626  are provided to prevent rotation of the coil, each guide  626  riding along an interior edge of an adjacent extension  624 . The proximal end of the device  602  includes apertures  618  through which the coil leads  616  are routed and one or more additional apertures  620  to promote air flow during actuation. In some applications a sample vial is swapped out for a drug vial between sample collection and injection. Alternatively or in addition, analysis of the sample may be performed by a separate analyzer. 
     Because the Lorentz-force actuator is bi-directional, depending upon the direction of the coil current, the same device used to inject a substance can also be used to withdraw a sample. This is a beneficial feature as it enables the device to collect a sample. Referring to  FIG. 8A , an exemplary sampling, needle-free injector  700  is illustrated. The sampling injection device  700  includes a bi-directional electromagnetic actuator  702  abutting at one end a first piston  714 A. A sampling nozzle  711 A is coupled at the other end of a syringe  710 . The actuator  702  is powered by a power source  704 , such as a battery or suitably charged storage capacitor. The first piston  714 A is slidably disposed within a sampling syringe  710 , such that an electrical input signal applied to the actuator  702  withdraws the first piston  714 A away from the sampling nozzle  711 A. A sample can be collected form a biological body when the sampling nozzle  711 A is placed against a surface of the body during actuation. 
     Referring now to  FIG. 8B , once a sample has been collected, a movable syringe mount  708  can be re-positioned such that the sampling syringe  710  is aligned with an analyzer  706 . By the same motion, a second syringe  712  having a second piston  714 B and including a substance, such as a drug, is aligned with the actuator  702 . The mount  708  may be a rotary mount rotating about a longitudinal axis or a linear mount as shown. The analyzer  706  provides a control signal to the power source  704  responsive to the analyzed sample. The control signal causes the actuator  702  to push the second piston  714 B forward thereby expelling an amount of the substance responsive to the analyzed sample. Thus, the same device  700  can be used to both collect a sample and to inject a substance. 
     As already described, the needle-free device can be used to collect a sample from the body. An exemplary method of collecting a sample is illustrated in the flow diagram of  FIG. 9A . First, the surface is punctured using the needle free injector. (Step  800 ) Next, a sample is collected from the biological body again using the needle-free device. (Step  810 ) The collected sample is analyzed, for example to determine a physical property such as blood sugar. (Step  820 ) Any one or more of a number of different methods of analysis may be performed at this step. For example, analyses may include: (i) electrochemical techniques for the detection of glucose, such as a glucose oxidase test; and optical techniques, such as surface-enhanced Raman spectroscopy. The controller receives the results of the analysis and determines a dosage based on the analyzed sample. (Step  830 ) The determined dosage is administered to the biological body using the needle-free device. (Step  840 ). 
     In more detail, referring to the flow diagram of  FIG. 9B , the step of needle-free sample collection (Step  810 ) includes first injecting a substance to pierce the skin. (Step  812 ) For example, saline solution can be injected to pierce the skin. Next, a sample is withdrawn using the needle-free device by sucking a sample from the biological body into a reservoir of the device. If the sample is not sufficient in volume or constitution, the withdrawn sample of saline solution and blood, tissue, and interstitial fluid is re-injected into the biological body using the need free device. (Step  818 ) Steps  814  through  818  can be repeated until a suitable sample or bolus is obtained. In some embodiments, determination of the sufficiency of the sample may be determined beforehand according to a prescribe number of cycles. Alternatively or in addition, sufficiency of the sample may be determined during the course of the sampling process. 
     Exemplary drive currents that can be applied to the dynamically controllable electromagnetic actuator are illustrated in the plots of  FIGS. 10A and 10B . Referring first to  FIG. 10A , a sample actuation cycle is shown including an initial piercing phase in which a substantial positive current is applied to force a substance into the biological body creating a perforation. The piercing phase is followed by a sampling phase in which a lesser-magnitude current is applied in the opposite direction to collect a sample. Referring next to  FIG. 10B , a multi cycle sample is shown in which an initial piercing phase is followed by repeated sample and re-injection phases as described in relation to  FIG. 9B . 
     An alternative embodiment of a sampling injection device  900  is illustrated in  FIG. 11 . The device  900  includes two nozzles  914 A,  914 B each at opposing ends of the device with a controllable electromagnetic actuator  925  disposed therebetween. Each nozzle  914 A,  914 B is coupled at an external end of a respective syringe  912 A,  912 B, each syringe defining a respective reservoir  913 A,  913 B and each having a respective piston  910 A,  910 B slidably disposed therein. An internal end of each piston is coupled to a respective end of the actuator  925 , such that actuation in one direction causes one plunger  910 A to advance toward the distal nozzle  914 A creating a pressure within the reservoir  913 A adapted to inject a substance contained therein. The same actuation in the same direction causes the other plunger  910 B to withdraw away from the distal nozzle  914 B creating a vacuum within the reservoir  913 B to withdraw a substance into the reservoir  913 B. 
     The actuator  925  includes a movable coil assembly  904  and receives an electrical input signal from a controller  908  that is also coupled to a power source  909 . In some embodiments, the device  900  includes an analyzer  916  coupled to the controller  908  for analyzing a sample collected in the sampling reservoir  913 B. In operation, one end of the device can be used to collect a sample from a biological body as a result of a needle-free transfer across the surface of the biological body. The analyzer  916  may analyze the sample and provide a result to the controller  908 . The controller  908  may determine the parameters for a dosage of a substance to the biological body based on the analyzed sample. 
     The other end of the device can be used to administer a dosage of a substance to the biological body. The controller then provides an electrical input form the power source  909  to the actuator  925 , possibly under the control of a local or remote operator through an input/output interface. The actuator  925  moves a piston in the same direction according to the received input, creating a pressure and causing an injection through the injecting end of the device  900 . 
     In some embodiments, it is advantageous to provide a controllable needle-free injection device  1000  capable of administering multiple injections and/or samples in succession. Thus, actuation cycles occur with relatively short time delay between cycles adjacent. Such a device can be referred to as a multi-shot needle-free injection device. Multi-shot injections can occur within 30 milliseconds to 50 milliseconds per cycle, with an actuation (i.e., injection) cycle 10 milliseconds. Some multi-shot devices have a capability to deliver up to 500 injections per drug vial. 
     For example, referring to the schematic diagram of  FIG. 12 , a multi-shot, needle-free injection device  1000  includes an attached reservoir or ampoule  1002 . The device  1000  is applied to the surface of a biological body  1004  and a transdermal transfer is initiated a first location  1006  at which the tip of the device  1000  is placed. The process can be repeated at other locations in a general proximity with respect to each other thereby treating a substantial surface region  1008  of the biological body. In other applications, the same multi-shot device  1000  can be used to transdermally transfer a substance in each of multiple different biological bodies. Such applications would include inoculating a group of animals, one after another. 
     A plot of an exemplary coil drive current versus time for a multi-shot application is illustrated in  FIG. 13 . The current profile of an individual actuation cycle or period can be similar to any of those described earlier in relation to  FIGS. 3, 10A and 10B  separated by a user-selectable inter-shot delay. Although the same general input waveform is illustrated for each cycle, the device is capable of initiating different waveforms for each cycle. 
     An exemplary portable, multi-shot injection device  1100  is illustrated in  FIGS. 14A and 14B . The device  1100  includes a housing  1102  having a handle section  1104  that may include a trigger  1110 . The device also includes a nozzle  1006 , a reservoir or ampoule  1112  and a self-contained power source  1108 . In some embodiments, the device  1100  also includes a user interface  1114 . 
     Referring to the power source  106  in more detail, it is possible to charge a rechargeable power source, such as a rechargeable battery or storage capacitor. For example, recharging can be accomplished with solar cells, a dynamo, or inductive coupling. For example, the coil assembly  104  can be used in the inductive coupling to an external power source, the coupled source creating an electrical current within the coil assembly  104 , usable to charge the power source  106 . 
     In some embodiments, the device can be recharged using the electromagnetic actuator  125  itself. That is, mechanical movement of the coil assembly  104  through the magnetic field provided by the magnet assembly  105  (as might be accomplished by shaking or vibrating the device  100 ) produces an electrical current within the coil. The coil assembly  104  may be coupled to the power source  106  through a regulator or other suitable recharging circuit. Thus, electrical current induced within the coil assembly  104  by its movement through the magnetic field can be used to recharge the power source  106 . 
     An exemplary mechanical recharging device is illustrated in  FIG. 15 . The mechanical recharging unit  1200  includes a mechanical transducer, such as a vibrator  1204 , that oscillates a shaft  1206  back and forth. The shaft is coupled at one end to the vibrator  1204  and at the other end to an adapter fitting  1208  adapted to engage the forced-transfer member  110  of the device  1201 . The recharging unit  1200  also includes a mounting flange  1202  adapted to hold a device in engagement with the vibrator  1204  during a recharging period. As shown, a syringe is first removed so that the coil assembly can be oscillated through the magnetic field producing an electrical current in the coil  104 . The resulting current can be fad back into the power source  106  through a power conditioner  1210 . The power conditioner  1210  can include one or more of a rectifier, a voltage regulator, a filter, and a recharging unit. As shown, the magnet assembly  105  is coupled to the housing  102  through a mounting  1211 , such that the magnet remains fixed with respect to the moving coil assembly  104 . 
     The controllable nature of such a transdermal transfer device lends itself to automatic, or robotic injection. First, a forceful needle-free injection may be used to inject through the skin of a biological body, such as the relatively thick hide of a large mammal, such as a cow. As the injection is needle-free, there is no chance of a needle breaking within an animal, should the animal move during the course of an injection. Further, because a forceful needle-free injection can be accomplished in a fraction of a second, the duration of time during which an animal must remain immobile is greatly reduced. Thus, a mere bump of a nozzle on an animal combined with a momentary release may occur in such a short period of time, that it may even be done while the animal is mobile. 
     An exemplary needle-free injection system for administering a controlled dose of a substance to an animal is illustrated in  FIG. 16 . The system includes a needle-free transdermal transport device  1306  disposed at a distal end of an extendable arm  1304 . The proximal end of the arm  1304  may be connected to a rigid mount, such as a post or frame  1308 . A sensor  1310  may also be provided to identify an animal prior to administering a transdermal transfer. For example, the animal  1302  can include an identifying mark  1312 , such as a bar-code tag or a radio frequency identification (RFID) tag. The sensor  1310  can therefore include an interrogator adapted to read a bar-code or RFID tag. The sensor  1310  and the transdermal transport device  1306  are both coupled to a controller  1314 , which may include a processor. A power source  1316  is also coupled to the transdermal transfer device  1306  through the controller  1314 . 
     In some embodiments, the device includes another animal sensor, such as a force plate  1318  adapted to sense a physical property of the animal such as its weight. A guide, such as a gate  1324  can be provided to suitably position the animal  1302  during identification and dosage. The controller  1314  also receives an input from the sensor  1318  and generates a dosage control based on the animal identification and weight. For example, a growth hormone could be administered to a particular animal based on its identification and weight. 
     In some embodiments, the system also includes a communications interface  1320 . The communications interface can include a wireless interface  1322 , such as the wireless communications interface discussed above in relation to  FIG. 1 . Thus, the system can communicate with a remote user, processor, and/or database. 
     The operational features offered by the dynamically controllable Lorentz-force actuator support numerous and varied treatment options. Combining both a forceful injection capability with controllability, the same controllable needle-free transdermal transport device can be used to deliver varied injections. For example, the device can be used non-invasively to deliver intradermally into a surface layer or the skin, between different biological layers (e.g., along a cleavage plane), or a subcutaneous injection administered to the subcutis, a layer of skin directly below the dermins and epidermis. Non-axial needle-free injections are described in U.S. patent application entitled “Surface Injection Device” filed on Feb. 10, 2006 under Ser. No. 11/351,887, incorporated herein by reference in its entirety. The device may also be used to deliver an intramuscular injection administering a substance directly into a muscle. Still further, the device may be used to deliver intravenous infusion administering a drug directly into the bloodstream via a vein. 
     An exemplary application for injecting a substance into an anatomical joint is illustrated in  FIG. 17 . A portion of a human knee  1400  is shown as an example of a synovial joint  1402 . A synovial joint  1402  includes a viscous fluid  1406  which is contained inside the “synovial” membrane  1404 , or “joint capsule. In some treatments it is desirable to inject a substance into the viscous fluid  1406 . This requires a relatively deep injection also penetrating the synovial membrane  1404 . Heretofore, such an injection required the use of larger gauge needles to prevent bending or breaking of the needle. Unfortunately, the larger diameter needle tended to increase pain and discomfort to the patient. Using the controllable electromagnetic needle-free device, it is possible to accomplish such an injection delivering a substance  1414 . Namely, the substance  1414  stored in a syringe  1408  is expelled through a nozzle  1412 . A narrow jet is formed by the nozzle  1412 , directing a stream  1416  of the substance along a straight line path to a desired depth. Thus, the stream  1416  can be directed to the interior region of the joint  1402  piercing the synovial membrane  1404  and delivering the substance  1418  with less pain and without bending. 
     An alternative embodiment of a controllable needle-free injection device  1800  shown in  FIG. 18  including a bellows  1802  forming a reservoir therein. An electromagnetic actuator  1825  either compresses or expands the bellows  1802 , depending upon the direction of the electrical input current. A nozzle  1801  adapted for needle-free injection is in fluid communication with the bellows chamber  1802  such that a formulation stored within the chamber  1802  is forced through the nozzle  1801  when the bellows  1802  is compressed. The nozzle  1801  is generally held in a fixed relationship with respect to the stationary portion of the actuator  1825 , such the bellows is compressed between the movable portion of the actuator  1825  and the nozzle  1801 . 
     The bellows chamber  1802  can be configured for quick and easy removal and replacement within the injection device  1800 . For example, a bellows chamber  1802  can be inserted into and removed from a side of a housing  1810 . The housing  1810  can include a mechanical fastener that secures the bellows chamber  1802  to the coil assembly  1804 . For example, the mechanical fastener can include a blade (not shown) configured to engage a complementary notch in the bellows chamber. Alternatively or in addition, specially-configured bellows can be used that are axially compressible while being otherwise rigid in non-axial directions. 
     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.