WO2004041068A2

WO2004041068A2 - Guided capsule for wireless endoscopy, biopsy, and drug delivery

Info

Publication number: WO2004041068A2
Application number: PCT/US2003/034716
Authority: WO
Inventors: Kamran Mohseni
Original assignee: Regents Of The University Of Colorado
Priority date: 2002-10-31
Filing date: 2003-10-31
Publication date: 2004-05-21
Also published as: AU2003287392A8; AU2003287392A1; WO2004041068A3

Abstract

A microjet actuator assembly for use within a capsule adapted for self-propulsion through an animal body, or other fluidic environment. The microjet actuator assembly may be adapted for use to aid in self-propulsion of the capsule, eject a fluid therapeutic agent into a region of an animal body from a capsule, and collect a tissue sample from an animal body to store it within a capsule while in vivo. The microject actuator has: a cavity, at least one wall of which comprises a deformable member and a second wall of which has an aperture; and a driver for activating the deformable member to deform and change a volume size of the cavity, causing a fluid within the volume to eject out through the aperture and/or enter through the aperture; wherein the cavity aperture is in communication with a fluidic environment, such as an animal gastrointestinal system, outside of a housing for the capsule, permitting the fluid to also pass out of this housing.

Description

Guided Capsule for Wireless Endoscopy, Biopsy, and Drug Delivery

BACKGROUND OF THE INVENTION

In general, the present invention relates to in vivo scope techniques to view the stomach and large (colon) and small (duodenum, etc.) intestines and especially to the less-invasive wireless capsule-type endoscopy techniques, whereby no physical wire connections are employed to scope the inside of the gastrointestinal tract of a body. Traditional wireless capsule-type endoscopy techniques involve passive movement of a capsule containing a tiny camera, through the body organs. More-specifically, the instant invention is directed to several new features of a novel guided 'wireless' capsule for remote-controlled actuation and movement throughout the human body (and other mammals), such as throughout the gastrointestinal (Gl) system, including the stomach, large (colon) and small intestines, and all accessory organs (e.g. , duodenum, etc.). The new guided capsule further includes features for remote-control of localized in vivo therapeutic drug delivery, with the additional capacity for dosing therapeutic agents, as well as for remote-control of performing tissue-biopsy while the capsule is passing through the body. As one will readily appreciate in connection with the instant technical disclosure, applicant has designed a wireless remotely-guidable capsule having new capabilities, with unique features as detailed herein: microjet actuator/generator assemblies, therapeutic drug delivery /dosing mechanism(s), and tissue-biopsy collection mechanism(s). As shown, a capsule preferably has several microjet actuators having aperture exits located around a capsule housing to provide locomotion options in different directions (forward, aft, and rotation around a lateral axis in either direction, etc.).

Listed below are published manuscripts that depict the passive passing of a capsule though the gastrointestinal (Gl) tract; each one is silent as to a technique of active locomotion: (1) U.S. Pat. N- 5,604,531, of 18-Feb-1997, In vivo video camera system, describes a swallowable capsule with an optical system for imaging an area of interest; (2) WO 2003028224 A2, international ap N- PCT/IL02/00784, System and method for controlling a device in vivo; and (3) WO 00/22975 Al, international ap N— PCT/IL99/00554, A method for delivering a device to a target location. By way of further background, the following is offered: A technical discussion of the Given^® Imaging Ltd, Yoqneam, Israel M2A™ passive ingestible Gl tract capsule may be found at www.givenimaging.com/usa/product. Distinguishable

10/31/03 - 1 - from the technology disclosed in these manuscripts is the unique microjet modality of the invention that not only provides novel locomotion options, but also options for localized therapeutic agent dispensing and tissue sample/biopsy applications, in connection with a capsule intended for in vivo use. The inventor hereof has authored manuscripts that provide background mathematical analysis and technical discussion concerning the fluid motion of vortex ring formation: (1) K. Mohseni. Mixing and impulse extremization in microscale vortex formation. In Proceedings of the Fifth International Conference on Modeling and Simulation of Microsystems, San Juan, Puerto Rico, April 2002; (2) K. Mohseni and M. Gharib. A model for universal time scale of vortex ring formation. Phys. Fluids, 10(10): 2436-2438, 1998; and (3) K. Mohseni, H. Ran, and T. Colonius. Numerical experiments on vortex ring formation. J. Fluid Mech, 430:267-282, 2001.

SUMMARY OF THE INVENTION It is a primary object of the invention to provide a microjet actuator assembly for use within a capsule adapted for self-propulsion through an animal body or other fluidic environment. The microjet actuator assembly may be adapted for use to aid in the self-propulsion of the capsule, eject a fluid therapeutic agent into a region of an animal body from a capsule, and collect a tissue sample from an animal body to store it within a capsule while in vivo. Also contemplated and disclosed within the spirit and scope hereof are associated processes of employing the microject actuator assemblies within a capsule as well as a capsule adapted for self-propulsion through at least a portion of an animal's Gl system, utilizing at least one microject actuator.

Briefly described, the microject actuator assembly has a combination of unique features: (a) a cavity, at least one wall of which comprises a deformable member and a second wall of which has an aperture; (b) a driver for activating the deformable member to deform and change a volume size of the cavity, causing a fluid (liquid or gas) within the volume to eject through the aperture; and (c) the aperture of the cavity is in communication with an environment outside of a housing for the capsule, permitting the fluid to also pass out of this housing. The bulk of driver components are preferably located outside the cavity volume. In the case of in vivo use of a capsule, such as where the capsule is ingested the 'environment' may comprise all or a portion of an animal's Gl system. A capsule of the invention has a housing, a power source, and one or more microjet actuator assemblies secured therewithin. The microjet actuators located within a capsule may each be of the type adapted to aid in in vivo self-propulsion of the capsule; or one or more

10/31/03 - 2 - microject actuators may have been adapted for ejecting a therapeutic agent and/or for collecting and storing a tissue sample within the capsule.

As used throughout and for reference, "therapeutic" includes curative; healing (soothing); restorative; corrective; medicinal; salubrious (health-giving); remedial; and/or beneficial, whether in connection with normal or enhanced body functioning, and/or contributing to or for the cure of any malady. "Animal" as used throughout includes any multicellular organism having a body that can move voluntarily and actively acquire food and digest it internally, including human beings and other mammals, birds and fish. As one will appreciate, a capsule of the invention ingested by an animal will be appropriately sized to fit through and exit that animal. For example, a capsule intended for use within a large-sized mammal need not be as small as that sized for human use. As one will appreciate, a wide variety of operative fluid therapeutic agents, materials and configurations for the cavity and associated deformable members, driver mechanisms, membrane materials, capsule configurations and housing materials, suitable AC/cyclical and/or DC/steady-state power sources, cantilevered blade mechanism designs and suitable materials, patterns of microject actuator apertures located over a capsule, are all contemplated and available for use according to the invention disclosed hereby.

There are numerous further patentably distinguishing features of the actuator assemblies of the invention, whether incorporated within a capsule, and associated process(es) of using the microjet actuator assemblies: The deformable member may be a flexible diaphragm having a magnetic component, whereby an associated driver comprises a coil through which an alternating current is passed for performing the activating— this coil being located within a capsule housing and in proximity to, but not in contact with, the flexible diaphragm. A variable current, such as alternating current (AC), applied to the coil produces an associated variable, alternating electromagnetic field in the vicinity of the coil. A flexible diaphragm having a magnetic component in proximity to the coil is affected by this varying magnetic field, and can be activated to cyclically decrease-increase the cavity volume size in relation to AC frequency applied to the coil. In the event the deformable member comprises a diaphragm made of an electroactive polymer (see discussion of EAPs), the driver preferably comprises a current source for applying a current or potential directly to an electrode on the deformable member to activate it by biasing the electroactive polymer in such a manner /direction to change the cavity volume size.

10/31/03 • 3 - In order to perform an 'electrostatic actuation' the deformable member can comprise a flexible diaphragm having an electrically conductive component (such as at least one thin-plate/strip-elements, a conductive polymer, plurality of conductive particles/shavings, etc.), with an associated driver comprising (a) an electrically conductive electrode to which a potential is applied, and (b) a voltage source for applying a potential to, or biasing, the electrically conductive component of the diaphragm. In the electrostatic actuation case, by biasing the conductive component (thus, applying a voltage/potential difference between the fixed electrode of the driver and the flexible diaphragm) the diaphragm deflects, in turn changing the cavity's volume size. Alternating the potential difference results in the application of alternating force on the diaphragm causing it to cyclically deflect. The oscillation of the deformable member results in micro jets exiting the cavity aperture.

The deformable member can comprise a piezoelectric diaphragm whereby an associated driver comprises a current source to apply a current (biasing the PZT) to the piezoelectric diaphragm to activate it and change the cavity's volume size. Alternatively, the driver can comprise a separate piezoelectric (PZT) element located within the capsule housing and through which AC is passed for performing the activating— in this case, the flexible diaphragm need not have a magnetic or conductive component, and the piezoelectric element is in proximity to, but not in contact with, the flexible diaphragm.

The magnetic, electrically conductive, or PZT component may be embedded, laminated, permanently adhered or otherwise secured as part of the deformable member. The magnetic component may be made from suitable magnetized or magnetizable materials and comprise one or more elements made of a ferromagnetic material, a plurality of ferro-magnetic particles dispersed within the flexible diaphragm (e.g., particles embedded/suspended within a flexible polymer matrix), and so on. The electroactive polymer (EAP) may be selected from any of those that exhibit a physical response to electrical excitation or stimulation— e.g., change shape in response to an application of current/voltage— may be from either of the two identified groups: ionic and electronic EAPs. Electronic EAPs include ferro-electric polymers, electrets, dielectric elastomers and electrostrictive graft elastomers, and are driven by electric fields. The deformable member may comprise a first and second electrode-element each of which comprises a plurality of conductive particles or elements (e.g., made of carbon or other conductive metal, alloy, polymer, etc.) dispersed/suspended/embedded within a soft polymer matrix;

10/31/03 disposed therebetween is an electroactive polymer layer, made of a dielectric elastomer for example (e.g., forming a sort of flexible capacitor). In this configuration, current (whether DC or AC) is directly applied to at least one of the electrode-elements of the deformable member to activate it.

While a single outburst or jet of fluid though the aperture may be preferable— such as the case where the microjet actuator is employed to dispense a therapeutic agent or to collect a sample of tissue, in vivo— in the event a series of cyclical burst to propel the capsule through a fluidic environment is chosen and an alternating current is applied, preferably an AC frequency is selected so that the flexible diaphragm mechanically oscillates at a resonant frequency thereof. This results in a cyclical decreasing-and-increasing of the volume size, thus producing cyclical intakes and outbursts of fluid out the aperture and capsule housing. Several of the microjet actuator assemblies may be incorporated within a capsule and remotely-controllable from outside the fluidic environment within which the capsule is used. Preferably each microject actuator is located such that respective cavities are not in direct communication with a cavity of another microject actuator.

The cavity may be tubular in shape, a first open-end of which comprises the flexible diaphragm— whether covering the whole of the first open-end— with the aperture being opposite the flexible diaphragm. The aperture is sized and shaped to result, when the microjet is in use, a target jet burst speed, jet size, viscosity of fluid within the cavity, and so on (e.g., if the volume is pre-filled with a viscous therapeutic agent, to eject the agent may require a larger aperture, likewise, a larger aperture may be required if cantilevered blade assemblies are covering it for use to collect a tissue sample). The tubular cavity may have a cross-sectional shape selected from a variety of shapes such as a circle, square, rectangle, triangle, oblong, an irregular polygonal shape, and so on. Furthermore, in order to redirect ejected bursts of fluid out the aperture and capsule housing, the cavity aperture may be in communication the Gl system via a channel and an exit port in the capsule housing. This channel may be oriented such that an angle between an axis of the cavity aperture and an axis of the housing exit port is greater than zero-degrees and less than 180-degrees (e.g., in FIG. 2 this angle is labeled, 0., for reference).

The cavity volume can be pre-filled with a fluid comprising a therapeutic agent. To contain the agent within the volume until dispensed, the aperture can be covered with a membrane creating a hermetic seal. The membrane is preferably

10/31/03 adapted to rupture upon activating the deformable member/diaphragm to permit the fluid, stored within said volume, to eject out through said aperture. The therapeutic agent may be 'locally' released from within the capsule at a selected site or region within the animal body, such as somewhere within the Gl system of an animal.

In the event the microjet assembly is adapted for collecting a tissue sample, at least one cantilevered micro-blade is included to initially cover the aperture. Upon activating the deformable member, the cantilevered micro-blade may extend outwardly to collect a tissue sample within reach of its micro-blade or extend inwardly— depending upon the direction of activation of the diaphragm to initially decrease or increase cavity volume. The aperture may also be covered by more than one micro-blade; each pair of micro-blades preferably cantilevered from opposing edges of the aperture and in an initial overlap/closed position to, for example, retain a fluid (liquid or gas) that may have been pre-filled within the cavity volume. The cantilevered micro-blades are preferably further adapted to, after activating the deformable member to extend the micro-blades to collect a sample of tissue, flex back toward the aperture to store the severed tissue sample within the cavity.

Also characterized and associated with the microjet actuator assembly of the invention is a process for propelling a capsule through a gastrointestinal system, comprising the steps of: (a) providing the capsule with at least one microjet actuator assembly of the invention; (b) ingesting the capsule; and (c) activating the deformable member to cyclically deform and change a volume size of the cavity in relation to a frequency of an alternating current applied, the activating to cause a fluid within the volume to correspondingly cyclically eject through the aperture and out of a housing for the capsule to aid in the propelling while the capsule is in vivo.

Once a plurality of the microject actuator assemblies are located within and around the capsule housing, after ingesting the capsule, further including the step of remotely-controlling each microject actuator from outside the gastrointestinal system, to activate each respective deformable member to cyclically deform to correspondingly cyclically eject fluid out each respective aperture to position the capsule in proximity to a targeted region within the gastrointestinal system.

Also characterized is a process for ejecting a fluid therapeutic agent into a region of a gastrointestinal system from a capsule while in vivo, comprising the steps of: (a) providing the capsule with at least one microjet actuator assembly of the invention; (b) ingesting the capsule; and (c) activating the deformable member to

10/31/03 - 6 - deform and change a volume size of the cavity filled with the fluid therapeutic agent, causing a membrane covering the aperture to rupture, to eject the agent out through the aperture and out of a housing for the capsule.

Finally characterized is a process for collecting a tissue sample from a gastrointestinal system using a capsule while in vivo, comprising the steps of: (a) providing the capsule with at least one microjet actuator assembly of the invention; (b) ingesting the capsule; (c) activating said deformable member to deform and change a volume size of the cavity filled with a fluid, to eject the fluid out through the aperture and out of a housing for the capsule, causing at least one cantilevered micro-blade covering the aperture to extend outwardly to collect the tissue sample within reach of the micro-blade; and (d) the cantilevered micro-blade to flex back toward the aperture for storage of the tissue sample within the cavity.

As can and will be appreciated, certain of the many unique features, as well as the further-unique combinations thereof, supported and contemplated hereby within the spirit and scope of this disclosure, may provide a variety of advantages. The advantages of the new features and combinations disclosed hereby will be appreciated, especially by providers of medical and veterinary care and services, by perusing the instant technical discussion, including drawings, claims, and abstract, in light of drawbacks to traditional devices identified throughout, or as may be uncovered. The unique mechanisms and configurations provide design options and versatility to accommodate a wide variety of applications. The basic actuator structure is adaptable for supporting a wide variety of capsule shapes and sizes; and the novel features are adaptable for incorporation into capsule-shapes having a wide variety of known internal imaging mechanisms. The unique approach to provide remote-controllable multi-directional propulsion, drug delivery and tissue-biopsy capabilities for capsules used in wireless endoscopy, gives medical technicians an integrated diagnostic, therapeutic, and biopsy tool.

BRIEF DESCTIPTION OF THE DRAWINGS For purposes of illustrating the innovative nature plus the flexibility of design and versatility of preferred and alternative microjet actuator assemblies adaptable for use in connection with in vivo capsule-type endoscopy, etc., systems and associated technique(s) for in vivo capsule propulsion, therapeutic agent dispensing, and tissue sampling, supported and disclosed hereby, the invention will be better appreciated by reviewing accompanying drawings (in which like numeral

10/31/03 - 7 - designate like or similar parts). One will appreciate the features that distinguish the instant invention from known/traditional wireless-endoscopy, drug delivery and tissue biopsy techniques. The drawings have been included to communicate features of the innovative structures and mechanisms, plus associated techniques of the invention, as well as to demonstrate the unique approach taken, by way of example only, and are in no way intended to unduly limit the disclosure hereof.

FIG. 1 A schematically represents a capsule 10 of the invention within which three microjet actuator assemblies (12A,C,E) have been secured by way of example.

FIG. IB is a high level sectional view taken at IB - IB of FIG. 1A illustrating an alternative concentric positioning of microjet actuators (12A-D) around the capsule body 10 to aid in a multi-directional locomotion options.

FIG. 2 is a sectional schematic view, similar to FIG. IB depicting alternative structures for microject actuators (22A-B)— a direction of rotation 21C is shown.

FIGs. 3 A - 3B are schematic depictions of an actuator assembly of the invention 32 shown in at intake (FIG. 3A) and when the fluid ejects (FIG. 3B).

FIGs. 4A - 4B are schematic depictions of an actuator assembly of the invention 42 for dispensing a therapeutic agent, shown pre-filled (FIG. 4A) and when the fluid ejects (FIG. 4B).

FIGs. 5 A - 5B are schematic depictions of an actuator assembly of the invention 52 for collecting a tissue sample, shown pre-filled (FIG. 5A) and when the fluid ejects (FIG. 5B).

FIG. 6 schematically represents alternative capsule 60 within which several microject actuator assemblies have been located around the capsule body.

FIG. 7 represents another alternative capsule 70; multiple apertures and/or exit ports patterned around the capsule body are labeled (75A-E), for reference.

FIG. 8 is a schematic of a simplification of the Helmholtz cavity model: represented here is vortex ring formation at pinch-off, formed from a piston pushing a column of fluid (length L) through an orifice or nozzle of diameter D.

FIG. 9 depicts a human model within which a Gl system is sketched. FIGs. 10A - 10B isometrically represent an example of a portion of a deformable membrane in the form of a capacitor assembly 108 wherein an electroactive polymer layer is disposed between electrode-elements.

FIGs. 11A - 11B are isometric sectional views depicting an alternative cavity 132 of the invention having outer electrode elements that are electrically biased to activate the deformable diaphragm.

FIGs. 12 is a schematic depiction of an alternative actuator assembly 152 for collecting a tissue sample shown pre-filled, by way of example (see also FIG. 5A).

10/31/03 - 8 - FIG. 13 is an isometric sectional view depicting alternative cavity 253 with diaphragm 254 having a component 269B biased by potential N± , for example.

DETAILED DESCRIPTION OF EMBODIMENTS IN DRAWINGS By way of background as is well known, electric and magnetic fields are fundamentally fields of force that originate from electric charges. Whether a force field may be termed electric, magnetic, or electromagnetic hinges on the motional state of the electric charges relative to the point at which field observations are made. Electric charges at rest relative to an observation point give rise to an electrostatic (time-independent) field there. The relative motion of the charges provides an additional force field called magnetic. That added field is magnetostatic if the charges are moving at constant velocities relative to the observation point. Accelerated motions, on the other hand, produce both time- varying electric and magnetic fields termed electromagnetic fields. For general reference see the textbook, Engineering Electromagnetic Fields and Waves, Carl T. A. Johnk, John Wiley & Sons, 2^nd Edition (1988).

FIG. 1A schematically represents a capsule 10 of the invention within which microjet actuator assemblies 12A, 12C, 12E have been suitably secured, by way of example, to the interior of the capsule body such that each cavity 13A,C,E shares an exterior wall with the capsule. A respective aperture 15A,C,E through each wall, also directly exits the capsule body /housing. Opposite apertures 15A,C,E is a deformable member (e.g., flexible diaphragm) 14A,C,E. Each member 14, along with the other walls of that cavity 13, forms a volume thereof. Represented at 16A,C,E is a coil or electrode assembly adapted, in operation, to drive the activation of the deformable members 14A,C,E. Suitable power source may include batteries 17A - 17C and associated circuitry (not shown for simplicity) to provide a source of electrical current/power for the actuator assemblies 12A, 12C, 12E. In the event AC is required to activate the deformable member(s) 14A,C,E, suitable oscillator circuitry /AC generator will be included. Also labeled within the capsule housing 10 are known features of, for example, the Given^® Imaging Ltd. 's M2A™ passive ingestible, wireless, Gl tract capsule referenced above: a lens 98, LED's 97, a CMOS imager 96, and a transmitter and antenna assembly 99.

The sectional high-level schematic view in FIG. IB, taken at IB - IB of

FIG. 1A, illustrates one example of where microjet actuators 12A-D may be located around capsule 10 to aid in a multi-directional locomotion options. Two examples

10/31/03 - 9 - of locomotion options have been referenced 11 A, 11B. Exit ports in communication with cavity apertures 15A-D permit fluid within each respective cavity 13A-D to be expelled from capsule housing 10 once a respective deformable member 14A-D has been activated as further described and shown. Exit ports are preferably angled.

FIG. 2 is a high-level sectional schematic view, similar to that in FIG. IB, depicting alternative structures for two microject actuators 22 A, 22B. As oriented, a thrust direction (21A, 21B) against the capsule due to activation of each actuator 22A, 22B, and a corresponding direction of rotation 21C of the capsule are shown for reference. Here, a channel 26A,B between an aperture 25A,B through a wall of cavity 23A,B and an exit port 28A,B provides a mechanism by which fluid ejected out of a respective cavity's aperture 25 A, B is preferably redirected to produce thrust in a direction 2 IB that is not parallel with an axis of the aperture 25B (29B). For example, channel 26B is oriented such that an angle (labeled ) between the cavity aperture's axis (29B) and an axis of the housing exit port (29ep) is ~90-degrees; however, 0. may be selected anywhere between zero-degrees and 180-degrees. Suitable power source may include batteries 27 and associated circuitry (not shown).

FIGs. 3 A - 3B are high-level schematics of an actuator assembly 32 shown at intake 31 through aperture 35 of cavity 33 (FIG. 3 A) and when the fluid 31 is ejected from the aperture, shown as vortex rings 38 (FIG. 3B), upon activating the flexible diaphragm 34 by employing an associated suitable driver mechanism 36 to decrease the cavity volume— whether done on a one-time basis, or cyclically using AC generator, inverter, oscillator circuitry, etc. to provide an AC power supply.

FIGs. 4 A - 4B are high-level schematics of an actuator assembly 42 adapted for dispensing a therapeutic agent: Cavity 43 is shown pre-filled 41 (FIG. 4A) with membrane 45 hermetically covering aperture 45; upon activating the deformable member 44 employing a suitable driver mechanism 46, membrane 44 ruptures and fluid 41 is ejected exiting 48 aperture 45 into an outside environment (FIG. 4B). A magnetic or electroactive polymer component may be added, in the form of one or more elements or particles as generally referenced in FIGs. 3A-3B, 4A-4B at 39 and 49. If done so, corresponding driver(s) 36, 46 are employed. FIGs. 5A - 5B are high-level depictions of an actuator assembly 52 for collecting a tissue sample from tissue 59. Cavity 53 is shown pre-filled 51 (FIG. 5A) with two cantilevered blades 57A, 57B covering aperture 55. Upon activating the deformable member 54 employing a suitable driver mechanism 56, cantilevered micro-blades 57A-B extend

10/31/03 - 10 - outwardly due to pressure from ejected fluid 51, to collect a sample of tissue 59 within reach (FIG. 5B). As mentioned, driver 36, 46, 56 may comprise any suitable associated mechanism, e.g., coil with AC or DC power source to produce requisite EM field to activate the deformable member by one or more pulses.

FIG. 6 schematically represents an alternative capsule 60 within which several microject actuator assemblies, 32A-C, 42, 52A-B have been located around a capsule body. As mentioned, the flexibility of design is apparent: Depending upon the dosage(s), number of different drugs being dosed during passage of the capsule through an animal body (e.g., anesthetic, antibiotic, used along with an additional chemical therapy), and drug types, one or more dosing actuators 42 may be incorporated into a capsule. Likewise, one or more of the propulsion 32A-C and/or tissue-biopsy 52A-B type actuators may be incorporated into a capsule. FIG. 7 simply depicts that a pattern of combinations of microjet actuators may be located around a capsule body 70. Here, several apertures 75A-E of varying sizes have been labeled, for reference, to illustrate location of respective actuator assemblies.

FIG. 8 is a schematic of a simplification of the Helmholtz cavity model 82 (replicated in part by microjet actuator assemblies of the invention): Represented here is vortex ring formation 88, of particular interest is the pinch-off of the ring formed from a piston 84 pushing a column of fluid 81 (length L) through an orifice or nozzle 85 of diameter D. As reported by the inventor hereof in his earlier references (see above): A basic building block of the underwater locomotion in nature (fish, jellyfish, squid, etc.) and aerial flight (aircraft, birds, and insects) is vortex ring formation. FIG. 9 depicts a human model 90 within which a capsule (such as that depicted herein at 10, 20, 60, and 70) is actively passing through an environment that includes the human's Gl system— labeled 94 for reference.

FIGs. 10A - 10B are isometrics representing an example of a portion of a deformable membrane made of a flexible capacitor assembly 108 wherein an electroactive polymer layer is disposed between electrode-elements; FIG. 10A is unbiased and FIG. 10B depicts the laminate in a biased state. As reported, S. Ashley, "Artificial Muscles", Scientific American, October 2003, electroactive polymer materials (EAPs) that display physical response to electrical excitation or stimulation— change shape in response to electricity— may be sorted into 2 groups: ionic and electronic types. Ionic EAPs include ionic polymer gels, ionomeric polymer-metal composites, conductive polymers and carbon nanorubes, and work on

10/31/03 - 11 - the basis of electro-chemistry— the mobility or diffusion of charged ions. Ionic EAPs can run off batteries since low (even single-digit) voltages will make them deform/bend significantly. However, for some Ionic EAPs, as long as electricity is applied to the material, the material may keep moving/bending. Electronic EAPs such as ferro-electric polymers, electrets, dielectric elastomers and electrostrictive graft elastomers, are driven by electric fields. While they require relatively high voltages, electronic EAPs react quickly and deliver strong mechanical forces. Electronic EAPs require little current to hold a deflected/deformed position.

FIGs. 10A-10B depict EAP laminated layers in action (see also, S. Ashley,

"Artificial Muscles", Scientific American, October 2003): FIG. 10A depicts an example of "artificial muscle" material 108; it is comprised of a dielectric elastomer film (e.g., —30 to ~60 microns thick) disposed between compliant electrodes, shown by way of example as generally planar and within which conductive particles (e.g., carbon) are dispersed by suspension in a soft polymer matrix. When the material 108 is exposed to high- voltage electric fields, dielectric elastomers— such as silicones and acrylics— contract in the direction of the electric field lines and expand perpendicularly to the electric field lines. The element shown at 108 is configured in the form of a flexible capacitor— two charged parallel plates 114A, 114B sandwiching a dielectric elastomer layer 119. When power is on (voltage applied) as shown in FIG. 10B, the plate-elements 114A, 114B are attracted to each other and squeeze down on the central insulator 119, which in turn responds by expanding in area (arrows in FIG. 10B represent the direction of expansion of the inside layer). The carbon dispersed polymer plates serve as flexible electrodes. Dielectric elastomers are only one type of electroactive material suitable for use.

Piezoelectric (PZT) is defined as having the ability to produce a mechanical force when a voltage is applied, as in a PZT crystal— a voltage between certain faces of a PZT crystal produces a mechanical distortion of the material, and vice versa: mechanical stress causes crystals to electrically polarize. Thus, apply an electric current to a PZT element and it deforms; deform a PZT element and it generates electricity. Note that the shrinking and expansion of a PZT element is typically only a fraction of its total length. For example, when a stack of PZT disks (e.g., made of lead zirconate titanate) are activated with an AC, the stack beats ultrasonically and may visibly hop up and down. Typically PZT vibrating elements are be cut from a PZT material to form a plate, bar, ring, etc. , with electrodes attached to or supported near the element to excite one of its resonant frequencies.

10/31/03 - 12 - FIGs. 11A - 11B are isometric sectional views depicting an alternative cavity 132 of the invention having an electroactive material layer 119 disposed between outer electrode elements 114A, 114B which are depicted in an unbiased state (FIG. 11 A) and as electrically biased (FIG. 11B) to activate the deformable diaphragm member 134. By way of an alternative example, while a volume of cavity 133 is shown as increased by the activation of deformable member 134 as depicted in FIG. 11B to pull fluid 131 in from an environment outside the microjet actuator 132, the cavity volume is thereafter decreased by activation to unbias the member 134, thus, decreasing the volume to eject fluid 131 out of the cavity 133.

Alternative actuators 152 and 252 in FIGs. 12-13 may be used for collecting a tissue sample. In FIG. 12, actuator 152 is shown pre-filled (similar to that in FIG. 5A). To perform an electrostatic actuation (identified above) an electrode 156/256 is biased to maintain a potential difference between it and diaphragm 154/254. Alternating the potential on diaphragm 154/254 causes it to cyclically deform; and as schematically depicted in FIG. 13, the diaphragm (here, having a conductive component 269B secured to a flexible layer 269 A) can be pulled downward to initially increase the volume of the cavity 153/253 causing an inflow of fluid 151/251 and an extending of micro-blades 257A,B (or in FIG. 12 at 157A,B) inwardly along with pulling in a sample of tissue 259 for storage within the cavity 153/253. The diaphragm 154/254 may be comprised of a PZT element 269B to which AC is applied to oscillate diaphragm 154/254 (without needing an additional electrode at 156/256). The alternative actuator assemblies in FIGs. 11A,B and 13 are shown as square/rectangular in cross-sectional shape, by way of example only.

In connection with the processes contemplated, details of core and further unique and distinguishing features, according to the invention, are readily ascertainable by reviewing the accompanying figures and supporting text such that further visual depiction, by way of a formal process flow diagram, is deemed unnecessary. As mentioned above, the cavity of an actuator assembly (12, 22, 32, 42, 52, 62, 132) may be tubular in shape, a first open-end of which comprises the flexible diaphragm (14, 24, 34, 44, 54, 134)— whether covering the whole of the first open-end (34, 44, 54)— with the aperture being opposite the flexible diaphragm. The aperture (15, 25, 35, 45, 55, 135) is sized and shaped to result, when the microjet is in use, a target jet burst speed, jet size, viscosity of fluid within the cavity, and so on (e.g., if the volume is pre-filled with a viscous therapeutic agent,

10/31/03 - 13 - to eject the agent may require a larger aperture, likewise, a larger aperture may be required if cantilevered blade assemblies are covering it for use to collect a tissue sample). Overall size of the capsule may vary, and will depend upon size of the patient (i.e., physical size of environments through which the capsule will move), the number of functions performed by the capsule (and thus, the number of mechanisms incorporated within the capsule body), expected dose size, size and type of power source to handle anticipated load during a single in vivo use of the capsule, and so on. For example, as represented in FIGs. 1A-1B and 2, a capsule produced for human use may be on the order of roughly ~ 30 mm to less than ~ 10 mm.

Design parameter considerations for a microjet actuator assembly of the invention, for use as an aid in propelling a capsule, as a therapeutic agent dose delivery mechanism, and tissue-biopsy mechanism are outlined, below, by way of example only: Frequency and amplitude of diaphragm oscillations; Velocity profile of the diaphragm motion; Shape of the orifice or nozzle for the cavity; Orientation of the nozzle; Size, shape and geometrical characteristics of the cavity; Location of each cavity, of each type, on the capsule's body (e.g., relative location of the micojet actuator cavities with one another will affect overall capsule-body motion); and Rupture mechanism (material, thickness, shape, etc.) for the membrane used in connection with, especially, the drug delivery assembly.

While certain representative embodiments and details have been shown for the purpose of illustrating the invention, those skilled in the art will readily appreciate that various modifications, whether specifically or expressly identified herein, may be made to any of the representative embodiments without departing from the novel teachings or scope of this technical disclosure. Accordingly, all such modifications are contemplated and intended to be included within the scope of the claims. Although the commonly employed preamble phrase "comprising the steps of" may be used herein in a method or process claim, applicant does not intend to invoke 35 U.S.C. §112 6. Furthermore, in any claim that is filed herewith or hereafter, any means-plus-function clauses used, or later found to be present, are intended to cover at least all structure(s) described herein as performing the recited function and not only structural equivalents but also equivalent structures.

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Claims

What is claimed is:

1. A microject actuator assembly for use within a capsule adapted for self- propulsion through an animal body, the actuator assembly comprising:

(a) a cavity, at least one wall of which comprises a deformable member and a second wall of which has an aperture;

(b) a driver for activating said deformable member to deform and change a volume size of said cavity, causing a fluid within said volume to eject out through said aperture, said driver located within a housing for the capsule; and

(c) said cavity aperture in communication with an environment outside of said housing, permitting said fluid to pass out of said housing.

2. The microjet actuator of claim 1 wherein:

(a) said deformable member is a flexible diaphragm having a magnetic component;

(b) said driver comprises a coil through which an alternating current is passed for performing said activating, said coil located within said housing and in proximity to and not in contact with said flexible diaphragm; and

(c) said activating comprises cyclically changing said volume size in relation to a frequency of said alternating current.

3. The microjet actuator of claim 2 adapted for use to aid in the self-propulsion of the capsule while in vivo, and wherein:

(a) said magnetic component comprises an element made of a ferromagnetic material within said flexible diaphragm;

(b) said cyclically changing said volume size comprises mechanically oscillating said flexible diaphragm at a resonant frequency thereof; and

(c) said cavity is tubular in shape, a first open-end of which comprises said flexible diaphragm, said aperture being opposite said diaphragm.

4. The microjet actuator of claim 2 wherein:

(a) said magnetic component comprises a plurality of ferro-magnetic particles dispersed within said flexible diaphragm;

(b) said cyclically decreasing said volume size comprises mechanically oscillating said flexible diaphragm at a resonant frequency thereof;

10/31/03 - 15 - (c) said cavity is tubular in shape having a cross-section selected from the group consisting of a circle, square, rectangle, triangle, oblong, and an irregular polygonal shape; and

(d) said cavity in communication with said environment comprises a channel between said aperture and an exit port in said housing.

5. The microjet actuator of claim 1 wherein:

(a) said deformable member comprises a diaphragm made of an electroactive polymer;

(b) said driver comprises a current source for applying a current to said deformable member for performing said activating; and

(c) said activating comprises biasing said electroactive polymer to change said volume size.

6. The microjet actuator of claim 5 wherein:

(a) said electroactive polymer comprises a dielectric elastomer;

(b) said deformable member further comprises a first and second electrode-element each of which comprises a plurality of conductive particles dispersed within a soft polymer matrix, said dielectric elastomer having been disposed between said first and second electrode-elements;

(c) said current comprises an alternating current directly applied to at least one of said first and second electrode-elements of said deformable member;

(d) said activating comprises cyclically decreasing and increasing said volume size to mechanically oscillate said flexible diaphragm;

(e) said cavity in communication with said environment comprises a channel between said aperture and an exit port in said housing.

7. The microjet actuator of claim 1 wherein:

(a) said deformable member is a flexible diaphragm having an electrically conductive component;

(b) said driver comprises an electrically conductive electrode to which an electrode-potential is applied and a voltage source for applying a diaphragm-potential to said electrically conductive component; and

(c) said activating comprises biasing said electrically conductive component to change said volume size.

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8. The microjet actuator of claim 1 wherein:

(a) said deformable member is a flexible diaphragm;

(b) said driver comprises a piezoelectric element through which an alternating current is passed for performing said activating, said piezoelectric element located within said housing and in proximity to and not in contact with said flexible diaphragm; and

9. The microjet actuator of claim 1 wherein:

(a) said deformable member comprises a piezoelectric diaphragm;

(b) said driver comprises a current source for applying a current to said piezoelectric diaphragm;

(c) said activating comprises biasing said piezoelectric diaphragm to change said volume size; and

(d) said cavity is tubular in shape, a first open-end of which comprises said flexible diaphragm, said aperture being opposite said diaphragm, and said tubular shape having a cross-section selected from the group consisting of a circle, square, rectangle, triangle, oblong, and an irregular polygonal shape.

10. The microjet actuator of claim 1 wherein:

(a) said deformable member is a flexible diaphragm comprising a component made of a material selected from the group consisting of a magnetic material, a piezoelectric material, and an electrically-conductive material;

(b) said cavity in communication with said environment comprises a channel between said aperture and an exit port in said housing; and

(c) an angle between an axis of said aperture and an axis of said exit port is greater than zero-degrees and less than 180-degrees.

11. The microjet actuator of claim 1 wherein:

(a) said deformable member is a flexible diaphragm;

(b) said volume is pre-filled with said fluid, said fluid comprises a therapeutic agent; and

10/31/03 - 17 - (c) covering said aperture is a membrane creating a hermetic seal, said membrane adapted to rupture upon said activating to permit said fluid, being stored within said volume, to eject out through said aperture.

12. The microjet actuator of claim 11 having been secured within the capsule, and wherein:

(a) said environment comprises a gastrointestinal system of the animal body;

(b) the capsule is positioned in proximity to a region within said gastrointestinal system; and

(c) upon performing said activating, said therapeutic agent passes out of said housing and into said region.

13. The microjet actuator of claim 1 wherein:

(a) said deformable member is a flexible diaphragm;

(b) covering said aperture is at least one cantilevered micro-blade; and

(c) upon said activating, said cantilevered micro-blade extends outwardly to collect a tissue sample within reach of said micro-blade, for storage within said volume of said cavity.

14. The microjet actuator of claim 13 wherein:

(a) said aperture is further covered by a second micro-blade, each said micro-blade cantilevered from an opposing edge of said aperture and in an initial position to contain said fluid, said fluid having been pre-filled within said volume; and

(b) said cantilevered micro-blades further adapted to, after said activating to collect said tissue sample, flex back toward said aperture for said storage of said tissue sample.

15. The microjet actuator of claim 1 wherein:

(a) said deformable member is a flexible diaphragm;

(b) covering said aperture is at least one cantilevered micro-blade;

(c) upon said activating, said fluid, first, enters said volume and said cantilevered micro-blade extends inwardly such that a tissue sample is collected and when said fluid within said volume ejects out, said tissue sample gets stored within said volume.

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16. A capsule adapted for self-propulsion through at least a portion of a gastrointestinal system of an animal body, the capsule comprising: a capsule housing; a microjet actuator assembly secured within said housing, said microjet actuator comprising:

(b) a driver for activating said deformable member to deform and change a volume size of said cavity, causing a fluid within said volume to eject out through said aperture; and

(c) said cavity aperture in communication with the gastrointestinal system, permitting said fluid to pass out of said housing to aid in the self- propulsion of the capsule while in vivo; and a power source.

17. The capsule of claim 16 wherein the self-propulsion is remotely-controllable from outside the gastrointestinal system; and further comprising a second microjet actuator comprising:

(a) a second cavity, at least one wall of which comprises a deformable member and a second wall of which has a second aperture;

(b) a second driver for activating said deformable member to deform and change a second volume size of said second cavity, causing a second fluid within said second volume to eject out through said second aperture;

(c) said second cavity aperture in communication with the gastrointestinal system, said second fluid comprises a therapeutic agent being stored within said second volume; and

(d) covering said second aperture is a membrane creating a hermetic seal, said membrane adapted to rupture upon said activating to permit said therapeutic agent to eject out through said second aperture.

18. The capsule of claim 16 further comprising a second microjet actuator comprising:

(b) a second driver for activating said deformable member to deform and change a second volume size of said second cavity;

10/31/03 - 19 - (c) said second cavity aperture in communication with the gastrointestinal system;

(d) covering said aperture is at least one cantilevered micro-blade; and

(e) upon said activating, said cantilevered micro-blade is extended to collect a tissue sample for storage within said second volume of said second cavity.

19. The capsule of claim 16 further comprising a plurality of said microjet actuator assemblies remotely-controllable from outside the gastrointestinal system, each said microject actuator located such that each said cavity is not in direct communication with another of said cavities; and wherein the animal body is that of a human.

20. A process for propelling a capsule through a gastrointestinal system, the process comprising the steps of:

(a) providing the capsule with a microjet actuator assembly comprising a cavity, at least one wall of which comprises a deformable member and a second wall of which has an aperture;

(b) ingesting the capsule; and

(c) activating said deformable member to cyclically deform and change a volume size of said cavity in relation to a frequency of an alternating current applied, said activating to cause a fluid within said volume to correspondingly cyclically eject out through said aperture and out of a housing for the capsule to aid in the propelling while the capsule is in vivo.

21. The process of claim 20 further comprising the step of:

(a) locating a plurality of said microject actuator assemblies within and around the capsule housing; and

(b) after said step of ingesting, remotely-controlling, from outside the gastrointestinal system, each said microject actuator and activating each said deformable member to cyclically deform to correspondingly cyclically eject fluid out each said aperture to position the capsule in proximity to a selected region within the gastrointestinal system.

10/31/03 - 20 -

22. A process for ejecting a fluid therapeutic agent into a region of a gastrointestinal system from a capsule while in vivo, the process comprising the steps of:

(b) ingesting the capsule; and

(c) activating said deformable member to deform and change a volume size of said cavity filled with the fluid therapeutic agent, causing a membrane covering said aperture to rupture, to eject the agent out through said aperture and out of a housing for the capsule.

23. A process for collecting a tissue sample from a gastrointestinal system using a capsule while in vivo, the process comprising the steps of:

(b) ingesting the capsule;

(c) activating said deformable member to deform and change a volume size of said cavity filled with a fluid, to eject said fluid out through said aperture and out of a housing for the capsule, causing at least one cantilevered micro-blade covering said aperture to extend outwardly to collect the tissue sample within reach of said micro-blade; and

(d) after said activating, said cantilevered micro-blade to flex back toward said aperture for storage of the tissue sample within said cavity.

2$. A process for collecting a tissue sample from a gastrointestinal system using a capsule while in vivo, the process comprising the steps of:

(b) ingesting the capsule; and

(c) activating said deformable member to deform and change a volume size of said cavity to fill with a fluid from outside of a housing for the capsule, causing at least one cantilevered micro-blade covering said aperture to extend and collect the tissue sample for storage within said cavity upon the flex back of said micro-blade toward said aperture.

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