Abstract:
An ophthalmic injection device has a dispensing chamber housing, a needle fluidly coupled to a dispensing chamber, a power source for providing current to the dispensing chamber housing, a controller for controlling the power source, and a housing at least partially enclosing the dispensing chamber housing, the power source, and the controller. The dispensing chamber housing is made of a shape memory alloy and has an inner surface defining a dispensing chamber for receiving a quantity of a substance. The controller directs a first current to the dispensing chamber housing to heat the substance contained in the dispensing chamber and a second current to the dispensing chamber housing to alter the shape of the dispensing chamber housing to deliver the substance.

Description:
RELATED APPLICATIONS 
     This application is a non-provisional of U.S. Patent Application No. 60/921,497 filed Oct. 16, 2006, U.S. Patent Application No. 60/921,498 filed Oct. 16, 2006, U.S. Patent Application No. 60/921,499 filed Oct. 16, 2006, and is a continuation-in-part of U.S. patent application Ser. No. 11/435,906 filed May 17, 2006, now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates to a medical device and more particularly to an ophthalmic drug delivery device using a shape memory alloy. 
     Several diseases and conditions of the posterior segment of the eye threaten vision. Age related macular degeneration (ARMD), choroidal neovascularization (CNV), retinopathies (e.g., diabetic retinopathy, vitreoretinopathy), retinitis (e.g., cytomegalovirus (CMV) retinitis), uveitis, macular edema, glaucoma, and neuropathies are several examples. 
     These, and other diseases, can be treated by injecting a drug into the eye. Such injections are typically manually made using a conventional syringe and needle.  FIG. 1  is a perspective view of a prior art syringe used to inject drugs into the eye. In  FIG. 1 , the syringe includes a needle  105 , a luer hub  110 , a chamber  115 , a plunger  120 , a plunger shaft  125 , and a thumb rest  130 . As is commonly known, the drug to be injected is located in chamber  115 . Pushing on the thumb rest  130  causes the plunger  120  to expel the drug through needle  105 . 
     In using such a syringe, the surgeon is required to puncture the eye tissue with the needle, hold the syringe steady, and actuate the syringe plunger (with or without the help of a nurse) to inject the fluid into the eye. The volume injected is typically not controlled in an accurate manner because the vernier on the syringe is not precise relative to the small injection volume. Fluid flow rates are uncontrolled. Reading the vernier is also subject to parallax error. Tissue damage may occur due to an “unsteady” injection. Reflux of the drug may also occur when the needle is removed from the eye. 
     An effort has been made to control the delivery of small amounts of liquids. A commercially available fluid dispenser is the ULTRA™ positive displacement dispenser available from EFD Inc. of Providence, R.I. The ULTRA dispenser is typically used in the dispensing of small volumes of industrial adhesives. It utilizes a conventional syringe and a custom dispensing tip. The syringe plunger is actuated using an electrical stepper motor and an actuating fluid. Parker Hannifin Corporation of Cleveland, Ohio distributes a small volume liquid dispenser for drug discovery applications made by Aurora Instruments LLC of San Diego, Calif. The Parker/Aurora dispenser utilizes a piezo-electric dispensing mechanism. Ypsomed, Inc. of Switzerland produces a line of injection pens and automated injectors primarily for the self-injection of insulin or hormones by a patient. This product line includes simple disposable pens and electronically-controlled motorized injectors. 
     U.S. Pat. No. 6,290,690 discloses an ophthalmic system for injecting a viscous fluid (e.g. silicone oil) into the eye while simultaneously aspirating a second viscous fluid (e.g. perflourocarbon liquid) from the eye in a fluid/fluid exchange during surgery to repair a retinal detachment or tear. The system includes a conventional syringe with a plunger. One end of the syringe is fluidly coupled to a source of pneumatic pressure that provides a constant pneumatic pressure to actuate the plunger. The other end of the syringe is fluidly coupled to an infusion cannula via tubing to deliver the viscous fluid to be injected. 
     It would be desirable to have a portable hand piece for injecting a drug into the eye that includes reliable technology using few parts. Shape memory alloy provides a technology that can be adapted for such use. The hand piece may be a single piece unit or a two-piece device. Placing the more expensive components, including electronics and a drive mechanism, in a reusable assembly, while keeping the sterile components in a disposable assembly, improves the efficiency and cost-effectiveness of a drug delivery system. However, a single piece device with a relatively simple structure is also feasible. Such a system provides numerous benefits over prior art injectors. 
     SUMMARY OF THE INVENTION 
     In one embodiment consistent with the principles of the present invention, the present invention is an ophthalmic injection system having a tip segment and a limited reuse assembly. The tip segment includes a dispensing chamber housing, a needle fluidly coupled to a dispensing chamber, and a first housing at least partially enclosing the dispensing chamber housing. The dispensing chamber housing is made of a shape memory alloy. The inner surface defines a dispensing chamber for receiving a quantity of a substance. The limited reuse assembly includes a power source for providing current to the dispensing chamber housing, a controller for controlling the power source, and a second housing at least partially enclosing the power source and the controller. The controller directs a first current to the dispensing chamber housing to heat the substance contained in the dispensing chamber and a second current to the dispensing chamber housing to alter the shape of the dispensing chamber housing to deliver the substance. 
     In another embodiment consistent with the principles of the present invention, the present invention is an ophthalmic injection device having a dispensing chamber housing, a needle fluidly coupled to a dispensing chamber, a power source for providing current to the dispensing chamber housing, a controller for controlling the power source, and a housing at least partially enclosing the dispensing chamber housing, the power source, and the controller. The dispensing chamber housing is made of a shape memory alloy and has an inner surface defining a dispensing chamber for receiving a quantity of a substance. The controller directs a first current to the dispensing chamber housing to heat the substance contained in the dispensing chamber and a second current to the dispensing chamber housing to alter the shape of the dispensing chamber housing to deliver the substance. 
     In another embodiment consistent with the principles of the present invention, the present invention is a method of delivering a substance into an eye including receiving a first input indicating that a substance is to be heated, in response to the first input, sending a first current to a dispensing chamber housing made of a shape memory alloy to heat the substance contained therein, receiving a second input indicating that the substance is to be delivered, and sending a second current to the dispensing chamber housing to deliver the substance. 
     It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are intended to provide further explanation of the invention as claimed. The following description, as well as the practice of the invention, set forth and suggest additional advantages and purposes of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the invention and together with the description, serve to explain the principles of the invention. 
         FIG. 1  is a perspective view of a prior art syringe. 
         FIG. 2  is one view of an ophthalmic medical device including a disposable tip segment and a limited reuse assembly according to an embodiment of the present invention. 
         FIG. 3  is another embodiment of a limited reuse assembly according to the principles of the present invention. 
         FIG. 4  is cross section view of a disposable tip segment and a limited reuse assembly according to an embodiment of the present invention. 
         FIGS. 5A and 5B  are exploded cross section views of disposable tip segments for an ophthalmic medical device according to an embodiment of the present invention. 
         FIG. 6  is a cross section view of an ophthalmic injection device according to the principles of the present invention. 
         FIG. 7  is a flow chart of one method of delivering a substance into an eye using a shape memory alloy. 
         FIG. 8  is a flow chart of one method of delivering a substance into an eye using a shape memory alloy. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Reference is now made in detail to the exemplary embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like parts. 
       FIG. 2  is one view of an ophthalmic medical device including a disposable tip segment and a limited reuse assembly according to an embodiment of the present invention. In  FIG. 2 , the medical device includes a tip segment  205  and a limited reuse assembly  250 . The tip segment  205  includes a needle  210 , a housing  215 , and an optional light  275 . The limited reuse assembly  250  includes a housing  255 , a switch  270 , a lock mechanism  265 , and a threaded portion  260 . 
     Tip segment  205  is capable of being connected to and removed from limited reuse assembly  250 . In this embodiment, tip segment  205  has a threaded portion on an interior surface of housing  215  that screws onto the threaded portion  260  of limited reuse assembly  250 . In addition, lock mechanism  265  secures tip segment  215  to limited reuse assembly  250 . Lock mechanism  265  may be in the form of a button, a sliding switch, or a cantilevered mechanism. Other mechanisms for connecting tip segment  205  to limited reuse assembly  250 , such as those involving structural features that mate with each other, are commonly known in the art and are within the scope of the present invention. 
     Needle  210  is adapted to deliver a substance, such as a drug, into an eye. Needle  210  may be of any commonly known configuration. Preferably, needle  210  is designed such that its thermal characteristics are conducive to the particular drug delivery application. For example, when a heated drug is to be delivered, needle  210  may be relatively short (several millimeters) in length to facilitate proper delivery of the drug. 
     Switch  270  is adapted to provide an input to the system. For example, switch  270  may be used to activate the system or to turn on a heater. Other switches, buttons, or user-directed control inputs are commonly known and may be employed with limited reuse assembly  250  and/or tip segment  205 . 
     Optional light  275  is illuminated when tip segment  205  is ready to be used. Optional light  275  may protrude from housing  215 , or it may be contained within housing  215 , in which case, optional light  275  may be seen through a clear portion of housing  215 . In other embodiments, optional light  275  may be replaced by an indicator, such as a liquid crystal display, segmented display, or other device that indicates a status or condition of disposable tip segment  205 . For example, optional light  275  may also pulse on and off to indicate other states, such as, but not limited to a system error, fully charged battery, insufficiently charged battery or faulty connection between the tip segment  205  and limited use assembly  250 . While shown on tip segment  205 , optional light  275  or other indicator may be located on limited reuse assembly  250 . 
       FIG. 3  is another embodiment of a limited reuse assembly according to the principles of the present invention. Limited reuse assembly  250  includes a button  308 , a display  320 , and a housing  330 . Disposable tip segment  205  attaches to end  340  of limited reuse assembly  250 . Button  308  is actuated to provide an input to the system. As with switch  270 , button  308  may activate a heater or other temperature control device or initiate actuation of a plunger. Display  320  is a liquid crystal display, segmented display, or other device that indicates a status or condition of disposable tip segment  205  or limited reuse assembly  250 . 
       FIG. 4  is cross section view of a disposable tip segment and a limited reuse assembly according to an embodiment of the present invention.  FIG. 4  shows how tip segment  205  interfaces with limited reuse assembly  250 . In the embodiment of  FIG. 4 , tip segment  205  includes dispensing chamber housing  425 , tip segment housing  215 , thermal sensor  460 , needle  210 , dispensing chamber  405 , interface  530 , and tip interface connector  453 . Limited reuse assembly  250  includes power source  505 , controller  305 , limited reuse assembly housing  255 , interface  535 , and limited reuse assembly interface connector  553 . 
     In  FIG. 4 , dispensing chamber housing  425  is tubular or cylindrical in shape and is made of a shape memory alloy (“SMA”). Shape memory alloys, such as various Nitinol (a nickel-titanium alloy) alloys, hold a deformed shape at room temperature. When heated to a higher temperature, the SMA reverts to its non-deformed shape. In other words, a shape memory alloy (also known as a smart alloy or memory metal) is a metal that “remembers” its geometry. After an SMA has been deformed from its original atomic configuration, it regains its original geometry by itself during heating. These properties are due to a temperature-dependent martensitic phase transformation from a low-symmetry to a highly symmetric crystallographic structure. Those crystal structures are known as martensite and austenite. The three main types of SMA are copper-zinc-aluminum, copper-aluminum-nickel, and nickel-titanium (Ni—Ti) alloys. The temperatures at which the SMA changes its crystallographic structure are characteristic of the alloy, and can be tuned by varying the elemental ratios. 
     For a dispensing chamber housing  425  made out of Nitinol, the Nitinol is in a deformed shape at room temperature. In this deformed shape, the Nitinol has a martenistic crystal structure. In this deformed shape, dispensing chamber  405  has a higher volume and can hold a substance. When a current is passed through dispensing chamber housing  425 , its temperature rises. When the temperature of the Nitinol dispensing chamber housing  425  reaches 60 or 70 degrees Celsius, the Nitinol will revert to its non-deformed shape. In this process, the Nitinol changes from a martenistic crystal structure to an austenic crystal structure. In this non-deformed shape, dispensing chamber  405  has a lower volume than in the deformed shape. Therefore, a current can be passed through dispensing chamber housing  425  to initially heat a substance in it, and then to change the shape of dispensing chamber  405  to expel that substance. 
     Needle  210  is fluidly coupled to dispensing chamber  405 . As such, a substance contained in dispensing chamber  405  can pass through needle  210  and into an eye. Interface  530  connects dispensing chamber housing  425  with tip interface connector  453 . 
     Optional thermal sensor  460  provides temperature information to assist in controlling the operation of dispensing chamber housing  425 . Thermal sensor  460  may be located near dispensing chamber housing  425  and measure a temperature near dispensing chamber housing  425  or may be located in thermal contact with dispensing chamber housing  425 , in which case it measures a temperature of dispensing chamber housing  425 . Thermal sensor  460  may be any of a number of different devices that can provide temperature information. For example, thermal sensor  460  may be a thermocouple or a resistive device whose resistance varies with temperature. Thermal sensor is also electrically coupled to interface  530  or other similar interface. 
     In limited reuse assembly  250 , power source  505  is typically a rechargeable battery, such as a lithium ion battery, although other types of batteries may be employed. In addition, any other type of power cell is appropriate for power source  505 . Power source  505  provides current to dispensing chamber housing  425  to heat it and change its shape. Optionally, power source  505  can be removed from housing  255  through a door or other similar feature (not shown). 
     Controller  305  is typically an integrated circuit with power, input, and output pins capable of performing logic functions. In various embodiments, controller  305  is a targeted device controller. In such a case, controller  305  performs specific control functions targeted to a specific device or component, such as a temperature control device or a power supply. For example, a temperature control device controller has the basic functionality to control current delivered to dispensing chamber housing  425 . In other embodiments, controller  305  is a microprocessor. In such a case, controller  305  is programmable so that it can function to control more than one component of the device. In other cases, controller  305  is not a programmable microprocessor, but instead is a special purpose controller configured to control different components that perform different functions. While depicted as one component in  FIG. 4 , controller  305  may be made of many different components or integrated circuits. 
     Controller  305  is connected via interface  535  to limited reuse assembly interface connector  553 . Limited reuse assembly interface connector  553  is located on a top surface of limited reuse assembly housing  255 . In this manner, limited reuse assembly interface connector  553  is adapted to be connected with tip interface connector  453  to provide an electrical connection between tip segment  205  and limited reuse assembly  250 . 
     An interface between power source  505  and controller  305  allows controller  305  to control operation of power source  505 . In such a case, controller  305  may control the charging and the discharging of power source  505  when power source  505  is a rechargeable battery. 
     In operation, when tip segment  205  is connected to limited reuse assembly  250 , controller  305  controls the operation of dispensing chamber housing  425 . Controller  305  directs current from power source  505  to dispensing chamber housing  425 . When dispensing chamber housing  425  is made of Nitinol, a first current is sent to it to increase its temperature and heat a substance contained in dispensing chamber  405 . A second, higher current is subsequently sent to dispensing chamber housing  425  to cause it to change its shape and expel the substance through needle  210 . 
     A substance to be delivered into an eye, typically a drug suspended in a phase transition compound, is located in dispensing chamber  405 . In this manner, the drug and phase transition compound are contacted by the inner surface of dispensing chamber housing  425 . The phase transition compound is in a solid or semi-solid state at lower temperatures and in a more liquid state at higher temperatures. Such a compound can be heated by the application of current to dispensing chamber housing  425  to a more liquid state and injected into the eye where it forms a bolus that erodes over time. 
     In one embodiment of the present invention, the substance located in dispensing chamber  405  is a drug that is preloaded into the dispensing chamber. In such a case, tip segment  205  is appropriate as a single use consumable product. Such a disposable product can be assembled at a factory with a dosage of a drug installed. 
       FIGS. 5A and 5B  are exploded cross section views of disposable tip segments for an ophthalmic medical device according to an embodiment of the present invention. In  FIG. 5A , dispensing chamber housing  425  is in its deformed shape (its crystalline structure is martenistic). In  FIG. 5B , dispensing chamber housing is in its non-deformed shape (its crystalline structure is austenic). In  FIGS. 5A and 5B , an optional luer is also picture to secure needle  210 . 
     In  FIG. 5A , a first current is applied to dispensing chamber housing  425 . This first current is less than that required to heat dispensing chamber housing  425  to a point at which it changes shape. However, this first current heats dispensing chamber housing  425  to a temperature above room temperature but below the temperature at which it changes shape. In this manner, a substance located in dispensing chamber  425  is heated because it is in thermal contact with the interior surface of dispensing chamber housing  425 . 
     For example, when dispensing chamber housing is made of Nitinol, a first current may raise the temperature of dispensing chamber housing  425  to 50 degrees Celsius. At this temperature, a phase transition compound located in dispensing chamber housing can be “melted” to a more liquid state or to a viscosity suitable for injection into an eye. However, at this point, the dispensing chamber housing maintains its deformed shape (and the dispensing chamber  405  has a higher volume). 
     A second current can be applied to raise the temperature of dispensing chamber housing  425  (made of Nitinol) to above 60 or 70 degrees Celsius. At this temperature, dispensing chamber housing  425  changes shape as depicted in  FIG. 5B . The volume of dispensing chamber  405  is reduced, thus expelling a substance  559  that was contained in dispensing chamber  405 . In other words, after the phase transition compound located in dispensing chamber  405  is heated, the second current causes the volume of dispensing chamber  405  to decrease and expel the phase transition compound through needle  210  and into an eye. 
     The first current applied to the dispensing chamber housing  425  can be regulated to control the temperature of the substance contained in dispensing chamber  405 . For example, the amount of current (typically DC current) can be controlled to precisely control the temperature of dispensing chamber housing  425 . The more current applied to dispensing chamber housing  425 , the greater its temperature. Thermal sensor  460  provides temperature information to controller  305 , so that it can control the amount of current sent to dispensing chamber housing  425 . Controller  305  may employ any of a number of different control algorithms, such as, for example, a PID algorithm. 
     Likewise, the second current applied to dispensing chamber housing  425  can be regulated to control a dosage and rate of delivery of the substance in dispensing chamber  405 . A shape metal alloy, such as Nitinol, may transform its shape gradually over a temperature range. For example, the shape of dispensing chamber  425  may change over a range of 5 or 10 degrees Celsius. The precise control of the current applied to dispensing chamber housing  425  results in the precise control of the temperature of dispensing chamber housing  425 . In this manner, the transition of dispensing chamber housing  425  from a deformed state to a non-deformed state can be controlled. The control of the change in shape results in control of the rate of delivery of the substance. 
       FIG. 6  is a cross section view of an ophthalmic injection device according to the principles of the present invention. In  FIG. 6 , the injection device is integrated into a single unit. The single piece device of  FIG. 6  operates in the same manner as the two piece device previously described. In  FIG. 6 , the device includes dispensing chamber housing  425 , dispensing chamber  405 , needle  210 , thermal sensor  460 , interface  536 , controller  305 , power source  505 , and housing  216 . In  FIG. 6 , a single interface  536  is used instead of two separate interfaces ( 530  and  535 ) and two separate connectors ( 453  and  553 ). Housing  216  encloses the components pictured. 
       FIG. 7  is a method of delivering a substance into an eye using a shape memory alloy. In  710 , a first input indicating that a substance is to be heated is received. In  720 , a first current is directed to an SMA dispensing chamber housing to heat the substance in the dispensing chamber. In  730 , a second input is received indicating that the substance is to be delivered. In  740 , after the substance is heated, a second current is directed to the SMA dispensing chamber housing to change its shape and dispense the substance. 
       FIG. 8  is a method of delivering a substance into an eye using a shape memory alloy. In  805 , a connection between a tip segment and a limited reuse assembly is recognized. In  810 , a first input indicating that a substance is to be heated is received. In  815 , a first current is sent to the dispensing chamber housing. In  820 , a determination is made as to whether the substance has reached the proper temperature. If the substance has not reached the proper temperature, then in  825  the first current is controlled to properly heat the substance. If the substance has reached the proper temperature, then in  830 , a second current is sent to the dispensing chamber housing to change its shape and deliver the substance. In  835 , a determination is made as to whether the proper dosage has been delivered. If the proper dosage has been delivered, then in  840  an indication that the substance has been delivered is provided. If the proper dosage has not been delivered, then in  845  a failure indication is provided. 
     From the above, it may be appreciated that the present invention provides an improved system and methods for delivering precise volumes of a substance into an eye. The present invention provides a dispensing chamber housing made of a shape memory alloy that can heat and expel a substance. In one embodiment, a disposable tip segment that interfaces with a limited reuse assembly is employed. In another embodiment, a single unit is employed. The present invention is illustrated herein by example, and various modifications may be made by a person of ordinary skill in the art. 
     While the present invention is described in the context of a single-use drug delivery device, the present invention encompasses any injection device. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.