The present disclosure relates to elongated tubular devices, systems, and methods utilized in minimally invasive delivery of therapeutic fluids to internal cites within a patient. In particular, the present disclosure relates to targeted fluid delivery devices, systems, and methods that administer therapeutic fluids utilizing piezoelectrically actuated dispensing mechanisms.
Many therapeutic compounds have been developed to treat numerous conditions within the body. Unfortunately, many of these compounds are delivered orally or by injections such that the entire body experiences the effects of the compounds in a systemic manner. Efforts have been made to deliver smaller amounts of the compounds closer to the site of treatment. For instance, a drug-coated device may be inserted into a patient, relying on elution of the drug off the surface of the device for delivery. However, measuring the amount of drug dispensed in such a situation can be very difficult and it may not be possible to get the drug carrying stent as close to the diseased tissue as necessary. Alternatively, a needle may be used at the end of a minimally invasive catheter delivery system. For remote locations within the body, such as within the heart, blood vessels or organs, the size of the delivery system must be very small and flexible to gain access to the area needing treatment. In certain designs, as the needle attempts to penetrate the tissue, the catheter pushes away from the vessel wall making it almost impossible to insert the needle in the desired location. One approach to solve this problem has been to add hooks on the end of the delivery system to penetrate the vessel walls to maintain the position of the delivery catheter while the needle is advanced. These hooks, as well as the needle itself, cause trauma to the vessel walls. In addition, the bore of the needle may be large compared with the amount of the drug to be administered. Thus, measuring the precise amount of the drug dispensed is problematic.
Therefore, while there have been some significant improvements in targeted drug delivery, the existing fluid delivery systems have not been entirely satisfactory.
Embodiments of the present disclosure are directed to minimally invasive therapeutic fluid delivery devices, systems, and methods.
In some embodiments, a flexible therapeutic fluid delivery device is provided. The delivery device includes a flexible elongate member having a proximal portion and a distal portion. The flexible elongate member is configured for minimally invasive insertion into a patient. The delivery device further includes a chamber situated in the distal portion of the flexible elongate member, a piezoelectric actuator positioned adjacent to the chamber, and a plurality of electrical leads coupled to the piezoelectric actuator. In the delivery device, the chamber has an outlet configured to eject a therapeutic fluid, and a piezoelectric actuator is positioned adjacent to the chamber such that, when actuated, the piezoelectric actuator alters a volume of the chamber to eject a portion of the therapeutic fluid.
In some embodiments, a flexible therapeutic fluid delivery device is provided. The delivery device includes a flexible elongate member having a proximal portion and a distal portion, with a cylindrical section in the distal portion. The cylindrical section includes an array of chambers formed in a substrate, each of the chambers having an outlet permitting the ejection of a portion of a therapeutic fluid filling the chamber and an inlet. A portion of the substrate has electrical conductors. The cylindrical section further includes an array of piezoelectric actuators coupled to the electrical conductors, each piezoelectric actuator coupled to one of the array of chambers such that, when actuated, the piezoelectric actuator ejects the portion of the therapeutic fluid and a reservoir, containing therapeutic fluid, situated in the distal portion of the flexible elongate member and coupled to the inlet of each of the array of chambers.
In some embodiments, a method for applying a therapeutic fluid to a tissue within a patient using an elongated fluid delivery device is provided. The method includes steps of inserting the elongated fluid delivery device into a patient, the elongated fluid delivery device having an electrically actuated ejection system adjacent a distal end thereof and of positioning the distal end of the elongated fluid delivery device close to the tissue. The method further includes steps of actuating the ejection system to eject a portion of a therapeutic fluid with sufficient velocity to contact the tissue and of removing the elongated fluid delivery device from the patient.
Additional aspects, features, and advantages of the present disclosure will become apparent from the following detailed description.
Illustrative embodiments of the present disclosure will be described with reference to the accompanying drawings, of which:
For clarity of discussion, elements having the same designation in the drawings may have the same or similar functions. The drawings may be better understood by referring to the following Detailed Description.
For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to the embodiments illustrated in the drawings, and specific language will be used to describe the same. It is nevertheless understood that no limitation to the scope of the disclosure is intended. Any alterations and further modifications to the described devices, systems, and methods, and any further application of the principles of the present disclosure are fully contemplated and included within the present disclosure as would normally occur to one skilled in the art to which the disclosure relates. In particular, it is fully contemplated that the features, components, and/or steps described with respect to one embodiment may be combined with the features, components, and/or steps described with respect to other embodiments of the present disclosure. For the sake of brevity, however, the numerous iterations of these combinations will not be described separately.
As used herein, “flexible elongate member” or “elongate flexible member” includes at least any thin, long, flexible structure that can be inserted into the tubular passages, including arteries and veins, of a patient. While the illustrated embodiments of the “flexible elongate members” of the present disclosure have a cylindrical profile with a circular cross-sectional profile that defines an outer diameter of the flexible elongate member, in other instances all or a portion of the flexible elongate members may have other geometric cross-sectional profiles (e.g., oval, rectangular, square, elliptical, etc.) or non-geometric cross-sectional profiles. Flexible elongate members include, for example, guidewires and catheters. In that regard, catheters may or may not include a lumen extending along its length for receiving and/or guiding other instruments. If the catheter includes a lumen, the lumen may be centered or offset with respect to the cross-sectional profile of the device.
“Connected”, “coupled”, and variations thereof as used herein includes direct connections, such as being glued or otherwise fastened directly to, on, within, etc. another element, as well as indirect connections where one or more elements are disposed between the connected elements.
“Intravascular device”, as used herein includes hypotubes, catheters, guidewires, and other devices such as may be used by a doctor to provide various treatments, and to obtain data from vessels throughout the body.
“Therapeutic fluid” is intended to be a fluid, including emulsions containing particles, that may provide a therapeutic effect for a patient, such as but without limitation, drugs, biologics, cells, such as stem cells, enzymes, and chemical compounds. While many embodiments are described herein in relation to drug delivery, any therapeutic fluid can be delivered in a similar manner.
Referring now to
The controller 104 may be configured to supply power and/or electrical communication signals to various components in embodiments of steerable intravascular device 100. A fluid delivery component 110 is situated within a lumen within the distal portion 108 of the flexible elongate member 102 and provides small portions or doses of a therapeutic fluid to a site within a patient close to the distal portion 108 of flexible elongate member 102. The distal portion 108 may be steered using the controller 104 to bring the fluid delivery component 110 into a desired position. The controller 104 may also be used to activate the fluid delivery component 110 to eject a portion of the therapeutic fluid. In some embodiments, the fluid delivery component 110 is configured entirely within the flexible elongate member 102; while in other embodiments, a portion of the fluid delivery component 110 may protrude beyond a distal end of the flexible elongate member 102. In some embodiments the therapeutic fluid is a conventional pharmaceutical, chemical compounds, or a biologic; while in other embodiments the therapeutic fluid includes cells, such as stem cells, or other bio-entities. When the patient is suffering from a malady, a physician may carefully guide the fluid delivery component 110 to a site within the patient requiring treatment and dispense an amount at required. The device may further include an imaging component 120 such as an ultrasound transducer, disposed adjacent to the distal end 108. The imaging component 120 aids the physician in targeting the tissue for treatment.
Referring now to
As mentioned,
As will be disclosed below, some embodiments of fluid delivery component 110 do not include paired piezoelectric elements, but instead include a single piezoelectric element that is constrained in such a manner that activation of the piezoelectric element causes the volume of the chamber to change in such a way that a force is applied to the therapeutic fluid contained in the volume.
A distal end of the chamber includes a tapered outlet or nozzle 404. The tapering may serve to better channel the force exerted by the actuator components 202 and 204 as they return to their dormant state and shape, thereby creating a focused jet or stream of fluid exiting the nozzle 404. The fluid delivery component 110 also includes a reservoir connector 406 that allows the chamber 402 to be in fluid communication with a reservoir containing a larger amount of the therapeutic fluid. As the chamber 402 expands when subjected to an activation energy, fluid flows from the reservoir through the reservoir connector 406 through a check valve 408 and into the chamber 402. As may be seen in
The expelled portion of therapeutic fluid is a short stream or droplet 412 expelled with adequate force to bring it into contact with a targeted tissue near the distal portion 108 of flexible elongate member 102. Droplet 412 may contain a volume of less than about a microliter. In some embodiments, the droplet 412 has a volume from about 5 to about 25 picoliters In general, the volume of droplet 412 may range in size from one or more picoliters to one or more microliters. The velocity at which droplet 412 is ejected from the chamber 402 may vary according to the dimensions of chamber 402 and with the amount of activation energy supplied. For example, droplet 412 may be expelled at a velocity of about 10 to about 25 meters per second. In some embodiments, the velocity may be even greater by changing the return force of the piezoelectric actuator components 202 and 204 and/or the shapes of nozzle 404 and chamber 402. Droplet 412 may be expelled with sufficient force to cause it to penetrate a depth into the target tissue. The velocity of the expelled droplet 412 is related to the activation energy applied to the fluid delivery component 110 such that a larger activation energy produces a higher velocity. A higher velocity may, in turn, cause the droplet 412 to penetrate deeper into the target tissue.
The embodiment of fluid delivery component 110 depicted in
As depicted in
Where the activation energy is lower, droplet 520 may be ejected with sufficient velocity to contact the target tissue nearby the fluid delivery component 500. When the activation energy is higher, the droplet 520 may be ejected with sufficient velocity to penetrate a certain depth into the target tissue thereby delivering a small, controlled amount of a drug, stem cells, or another therapeutic fluid into the tissue without a needle. Avoiding the use of a needle may facilitate recovery and help limit damage to the tissue being treated. Also, given the speed of the ejection, and the difference in mass associated with the droplet 520 and a catheter containing the fluid delivery component 500, the catheter “floating” within a blood vessel or a cardiac chamber will remain substantially stationary. This may obviate a need of including stabilizing features to hold the catheter close to the tissue of interest.
A set of electrical leads 518A may be formed on a top surface of the second substrate prior to or after the etching or milling process used to create chambers 508. A first piezoelectric material layer may be formed over or positioned over the additional substrate (used to form the piezoelectric elements 504B), followed by a second piezoelectric material layer in some embodiments (used to form the piezoelectric elements 504A). The first and second piezoelectric material layers may then be diced or etched to create a plurality or an array of actuator components 502, one actuator component 5002 per chamber 508 included in the array 600. In some embodiments, the second substrate forming chambers walls 506 is etched or milled only part way therethrough, such that some of the material of the additional substrate 506 remains to form the top surface of each chamber 508. This top surface being situated between the bottom of the actuator components 502 and the chambers 508. Thereafter, an additional set of electrical leads 518B are formed over the second piezoelectric material layer to provide a further electrical contact to each of actuator components 502. Prior to the formation of the additional set of electrical leads, a passivation, isolation, and/or insulation layer may be formed over the second piezoelectric material layer to provide electrical contact at a specific, limited location on the second piezoelectric material layer.
The interconnection circuitry comprises conductor lines deposited upon the surface of the flex circuit 702 between a set of integrated circuit chips 704 and a set of actuatable chambers 706. In the depicted embodiment, chambers 704 are substantially similar to the chambers 508 of
The width “W” of the individual conductor lines of the metallic circuitry (on the order of one-thousandth of an inch) is relatively thin in comparison to the typical width of metallic circuitry deposited upon a film or other flexible substrate. On the other hand, the width of the individual conductor lines is relatively large in comparison to the width of transmission lines in a typical integrated circuit. The layer thickness “T” of the conductor lines between the integrated circuit chips 704 and the array of chambers 706 is preferably 2-5 microns. This selected magnitude for the thickness and the width of the conductor lines enables the conductor lines to be sufficiently conductive while maintaining relative flexibility and resiliency so that the conductor lines do not break during re-shaping of the flex circuit 702. For example, the conductor lines do not break during a re-shaping of the flex circuit 702 into a cylindrical shape.
In the depicted embodiment, the thickness of the substrate of flex circuit 702 is from about 12.5 microns to about 25.0 microns. However, the thickness of the substrate is generally related to the degree of curvature in the final assembled fluid delivery component and may be thinner or thicker accordingly. The thin substrate of the flex circuit 702, as well as the relative flexibility of the substrate material, enables the flex circuit 702 to be wrapped into a generally cylindrical shape after the integrated circuit chips 704 and the array of chambers 706 have been mounted and/or formed and then attached to the metallic conductors of the flex circuit 702. Thus, a flexible substrate thickness may be on the order of several microns to well over 100 microns or more depending upon the flexibility requirements of the particular fluid delivery assembly configuration.
The flex circuit 702 is typically formed into a cylindrical shape in order to accommodate the space limitations of blood vessels in which an intravascular device containing the fluid delivery sub-assembly 700 may be inserted for treatment or through which the fluid delivery sub-assembly may pass en route to a target tissue site. In such instances the range of diameters for the cylindrically shaped fluid delivery component assembly is typically within the range of 0.5 millimeters to 3.0 millimeters. However, it is contemplated that the diameter of the fluid delivery component, when cylindrical, may be on the order of 0.3 millimeters to 5 millimeters. Furthermore, the fluid delivery sub-assembly 700 may also be incorporated into larger cylindrical assemblies, such as may be used on a distal end of flexible elongate member of an intravascular device and provide additional functionality.
After the fluid delivery sub-assembly 700 is formed into a cylinder, a cylindrical insert 802 is inserted into the cylinder formed by fluid delivery sub-assembly 700. The cylindrical insert 802 may serve multiple purposes. For instance, a pass-through 804 may be formed by the insertion of cylindrical insert 802 that allows electrical lines or support structures, like exemplary structure 805, to pass from one side of the fluid delivery sub-assembly 700 to the other. In embodiments of intravascular devices including fluid delivery sub-assembly 700 in addition to an imaging component situated at a distal tip of the intravascular device, communication and power supply lines may run through the pass through 804. Cylindrical insert 802 may also be used in providing a reservoir 806, by serving as a fluid retaining wall, that can be filled with therapeutic fluid. Reservoir 806 includes a space in between the cylindrical insert 802 and a top surface associated with the array of chambers 706. In some embodiments, a capping layer is formed over the fluid delivery sub-assembly 700 prior to re-shaping.
As discussed above in connection with
As depicted, a first portion 1010A is within the target tissue 1008. The volume or dosage of the therapeutic fluid and/or the velocity with which the portion is ejected from the fluid delivery component 1004 may be controlled by an amount of activation energy supplied to the piezoelectric actuator components or component within the fluid delivery component 1004. A second portion 1010B is depicted en route, as ejected, to the location occupied by the droplet or portion 1010A. While the end of the nozzle is shown spaced from the tissue for the purpose of illustration, it will be appreciated that in more preferred application, the nozzle will be in contact with the tissue to inhibit the blood from mixing with fluid being injected. Alternatively, a lower activation energy may be supplied to eject portion 1010B from the fluid delivery component 1004, such that portion 1010B does not penetrate the target tissue 1008 to the same depth reached by portion 1010A. Additionally, by controlling the activation energy, a droplet like portions 1010A and 1010B may be injected through one type of tissue or material and into another. For example, by controlling activating energy and/or a separation distance between the intravascular device 1002 and a target site, a droplet of therapeutic fluid may be injected along path 1012, through tissue 1008, and into the wall of vessel 1006 at target site 1014. Since only the fluid penetrates the tissue or tissues, as compared to a needle-based injection system, the catheter is self-retaining and can deliver repeated drug injections without the need for anchoring to the wall of vessel 1006.
In the depicted embodiment, the intravascular device 1102 further includes an imaging component 1106 that may be used to image the interior surface of a vessel 1108 within a patient. In this example, the imaging component 1106 is used to locate and identify an inflamed or otherwise damaged target tissue 1110. In one example, the imaging component 1106 can be a phased array intravascular ultrasound (IVUS) assembly. Through the use of a controller, like controller 104 of
In some embodiments, in addition to a fluid delivery component included in the intravascular device, there is also an imaging component. The imaging component, like the fluid delivery component, is positioned in a distal portion of the flexible elongate member of the intravascular device. The imaging component may be used to visualize at least a portion of the surroundings of the distal portion of the flexible elongate member of the intravascular device. The imaging component, which may be an intravascular ultrasound component, may be used to locate and to identify a site within the patient requiring treatment. In some instances of a diagnosis may be made using the imaging component. A particular tissue or portion of tissue within the patient may be chosen as the target tissue or target site in which to inject an amount of the therapeutic fluid. After the target tissue has been identified, in embodiments in which the fluid delivery component includes a plurality of piezoelectrically actuatable chambers, is specific one of the piezoelectrically actuatable chambers may be selected for actuation.
To actuate the chamber, an activation energy may be applied to a piezoelectric actuator component in communication with chamber such that the piezoelectric actuator component physically reacts to alter a volume of the chamber. The alteration of the volume of the chamber is used to apply a force to the therapeutic fluid therein to eject a portion of the therapeutic fluid from the chamber through an outlet. In some embodiments, the portion of therapeutic fluid ejected by a single actuated event may range in volume from about a microliter to about a picoliter. The force provided by the piezoelectrically actuated component may eject the portion of the therapeutic fluid with a velocity of about 10 to about 25 meters per second, which may be sufficient to penetrate the target tissue. Both the volume of the portion of therapeutic fluid and or the ejection velocity may be determined by an amount of activation energy applied to the piezoelectric actuator.
Persons skilled in the art will also recognize that the apparatus, systems, and methods described above can be modified in various ways. Accordingly, persons of ordinary skill in the art will appreciate that the embodiments encompassed by the present disclosure are not limited to the particular exemplary embodiments described above. In that regard, although illustrative embodiments have been shown and described, a wide range of modification, change, and substitution is contemplated in the foregoing disclosure. It is understood that such variations may be made to the foregoing without departing from the scope of the present disclosure. Accordingly, it is appropriate that the appended claims be construed broadly and in a manner consistent with the present disclosure.
The present application claims priority to and the benefit of U.S. Provisional Patent Application No. 61/794,002, filed Mar. 15, 2013, which is hereby incorporated by reference in its entirety.
Number | Date | Country | |
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61794002 | Mar 2013 | US |