Substance delivery system

Embodiments of a system including a remotely controlled substance delivery device and associated controller are described. Methods of use and control of the device are also disclosed. According to some embodiments, a delivery device or related device may be placed in an environment in order to pump a material into the environment or into an additional fluid handling structure within the device. Exemplary environments include a body of an organism, a body of water, or an enclosed volume of a fluid. The concentration of a substance in the fluid to be delivered may be modified by a remote control signal. In selected embodiments, a magnetic field, an electric field, or electromagnetic control signal may be used.

BACKGROUND

Implantable controlled release devices for drug delivery have been developed. Certain devices rely upon the gradual release of a drug from a polymeric carrier over time, due to degradation of the carrier. Polymer-based drug release devices are being developed that include a drug in a ferropolymer that may be heated by an externally applied magnetic field, thus influencing the drug release. MEMS based drug release devices that include integrated electrical circuitry are also under development, as are MEMS based systems for performing chemical reactions. Implantable delivery devices have been developed for drug delivery purposes. Wireless transmission of electromagnetic signals of various frequencies is well known in the areas of communications and data transmission, as well as in selected biomedical applications.

SUMMARY

The present application relates, in general, to the field of fluid delivery devices, systems, and methods. In particular, the present application relates to remotely controlled delivery devices in which the concentration of a material in a fluid to be delivered may be varied. Control signals may be carried between a remote controller and a delivery device in an environment by electrical, magnetic, or electromagnetic fields or radiation. Embodiments of a system including a remotely controlled delivery device and associated controller are described. Methods of use and control of the device are also disclosed. According to various embodiments, a delivery device may be placed in an environment in order to eject or release a material into the environment. Exemplary environments include a body of an organism, a body of water or other fluid, or an enclosed volume of a fluid. According to some embodiments, a delivery device may provide for delivery of a fluid into a downstream fluid-handling structure. The foregoing summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the drawings and the following detailed description.

DETAILED DESCRIPTION

In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrated embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here.

FIG. 1depicts a first exemplary embodiment of a delivery system10. In the embodiment ofFIG. 1, delivery system10includes delivery device12located in an environment14, (which in this particular example is a human body) and remote controller16. As used herein, the term “remote” refers to the transmission of information (e.g. data or control signals) or power signals or other interactions between spatially separated devices or apparatuses, such as the remote controller or the delivery system, without a connecting element such as a wire or cable linking the remote controller and the delivery system, and does not imply a particular spatial relationship between the remote controller and the delivery device, which may, in various embodiments, be separated by relatively large distances (e.g. miles or kilometers) or a relatively small distances (e.g. inches or millimeters). Delivery device12includes an electromagnetically responsive control element18that is responsive to an electromagnetic control signal generated by remote controller16.

FIG. 2depicts an embodiment of a delivery system20including a delivery device22controlled by remote controller24. In the embodiment ofFIG. 2, delivery device22includes pump26and delivery reservoir28which contains delivery fluid30. Remote controller24transmits electromagnetic control signal32to electromagnetically responsive control element34to control the concentration of primary material36in delivery fluid30. Pump26pumps delivery fluid30containing primary material36from delivery reservoir28via outlet37. Delivery device22also includes a body structure38.

FIG. 3depicts another embodiment of a delivery system40including a delivery device42controlled by remote controller44. In the embodiment ofFIG. 3, delivery device42includes pump46and delivery reservoir28, which contains delivery fluid30. Remote controller44transmits electromagnetic distribution control signal32to electromagnetically responsive control element34to control the concentration of primary material36in delivery fluid30. Remote controller44also transmits electromagnetic delivery control signal48to receiving element50in pump46to control the pumping of delivery fluid30from delivery reservoir28. Outlet37and body structure38are also included in delivery device48.

FIGS.4A and4BA illustrate in schematic form a delivery device60comprising a delivery reservoir62configured to contain a delivery fluid, the delivery reservoir having at least one outlet64through which the delivery fluid may exit the delivery reservoir; a delivery fluid66contained within the delivery reservoir62; a primary material68contained within the delivery reservoir62and having a controllable effective concentration in the delivery fluid; and at least one electromagnetically responsive control element70adapted for modifying the distribution of the primary material between a first active form carried in the delivery fluid and a second form in response to an incident electromagnetic control signal, the effective concentration being the concentration of the first active form in the delivery fluid. Delivery fluid may exit delivery reservoir66by diffusion, or by being moved out of delivery reservoir66by positive pressure applied to delivery reservoir62(e.g. by a pump) or negative pressure generated downstream of delivery reservoir62.FIG. 4Aillustrates a first state of electromagnetically responsive control element70, which causes primary material68to be in a first active form in delivery fluid66.FIG. 4Billustrates a second state of electromagnetic control element70, which causes the primary material to be in a second form68′, which is not an active form carried in delivery fluid66, but may be, for example, insoluble in delivery fluid66as depicted inFIG. 4B.

In order to modify the distribution of primary material between the first active form and the second form, the electromagnetically responsive control element used in this and other embodiments (e.g.,34inFIGS. 2 and 3or70inFIGS. 4A and 4B) may have various functional characteristics. In some embodiments, the electromagnetically responsive control element may include or form a heating element (e.g., a resistive element) or a cooling element (which may be, for example, a thermoelectric device). In some embodiments, the electromagnetically responsive control element may be an expanding element. In some embodiments, an electromagnetically responsive control element may include a receiving element such as an antenna or other geometric gain structure to enhance the receiving of an electromagnetic control signal transmitted from a remote control signal generator. The response of the electromagnetically responsive control element to an electromagnetic field may be due to absorption of energy from the electromagnetic signal or due to torque or traction on all or a portion of the electromagnetically responsive control element due to the electromagnetic field. The response will depend upon the intensity, the relative orientation and the frequency of the electromagnetic field and upon the geometry, composition and preparation of the material of the electromagnetically responsive control element. A response may occur on the macro level, on a microscopic level, or on a nanoscopic or molecular level. In some embodiments, the electromagnetically responsive control element may respond to the control signal by changing shape. In some embodiments, the electromagnetically responsive control element may respond to the control signal by changing in at least one dimension. The response of the electromagnetically responsive control element may include one or more of heating, cooling, vibrating, expanding, stretching, unfolding, contracting, deforming, softening, or folding globally or locally. In some embodiments, the electromagnetically responsive control element may be configured to selectively respond to an electromagnetic field having a specific frequency and orientation. Frequency selectivity may be conferred by appropriate selection of electromagnetically responsive control element size relative to the wavelength of the electromagnetic signal, while directional selectivity may be conferred by the configuration and orientation of the electromagnetically responsive control element.

Electromagnetically responsive control elements used in various embodiments of delivery devices and systems may include one or more electromagnetically active materials. The electromagnetically responsive control element may include a magnetically or electrically active material. Examples of magnetically active materials include permanently magnetizable materials, ferromagnetic materials such as iron, nickel, cobalt, and alloys thereof, ferrimagnetic materials such as magnetite, ferrous materials, ferric materials, diamagnetic materials such as quartz, paramagnetic materials such as silicate or sulfide, and antiferromagnetic materials such as canted antiferromagnetic materials which behave similarly to ferromagnetic materials; examples of electrically active materials include ferroelectrics, piezoelectrics, dielectric materials, including permanently ‘poled’ dielectrics and dielectrics having both positive and negative real permittivities, and metallic materials.

In some embodiments, the electromagnetically responsive control element may include a hydrogel, ferrogel, or ferroelectric. The electromagnetically responsive control element may include a polymer, ceramic, dielectric, or metal. The electromagnetically responsive control element may include various materials, such as polymers, ceramics, plastics, dielectrics or metals, or combinations thereof. In some embodiments, the electromagnetically responsive control element may include a polymer and a magnetically or electrically active component. In some embodiments, the electromagnetically responsive control element may include a shape memory material such as a shape memory polymer or a shape memory metal, or a composite structure such as a bimetallic structure.

In some embodiments, the electromagnetically responsive control element may include a polymer and an electrically active component (including highly polarizable dielectrics) or a magnetically active component (including ferropolymers and the like). In embodiments in which the electromagnetically responsive control element includes one or more electrically or magnetically active components, the electrically or magnetically active component may respond to an electromagnetic control signal in a first manner (e.g., by heating) and the response of the electromagnetically responsive control element may be produced in response to the electrically or magnetically active component (e.g. expansion or change in shape in response to heating of the electrically or magnetically active component). Electromagnetically responsive control elements may, in some embodiments, be composite structures.

FIG. 5depicts an example of an electromagnetically responsive control element100including a composite structure formed from a polymer102and multiple electrically or magnetically active components in the form of multiple particles104distributed through polymer102. In some embodiments, the electrically or magnetically active components may be heatable by the electromagnetic control signal, and heating of the electrically or magnetically active components may cause the polymer to undergo a change in configuration. An example of a magnetically responsive polymer is described, for example, in Neto, et al, “Optical, Magnetic and Dielectric Properties of Non-Liquid Crystalline Elastomers Doped with Magnetic Colloids”; Brazilian Journal of Physics; bearing a date of March 2005; pp. 184-189; Volume 35, Number 1, which is incorporated herein by reference. Other exemplary materials and structures are described in Agarwal et al., “Magnetically-driven temperature-controlled microfluidic actuators”; pp. 1-5; located at: http://www.unl.im.dendai.ac.jp/INSS2004/INSS2004_papers/OralPresentations/C2.pdf or U.S. Pat. No. 6,607,553, both of which are incorporated herein by reference.

As mentioned in connection withFIGS. 2-4B, the delivery device may contain a primary material (the material that is intended to be delivered to an environment or other downstream location) in a delivery fluid. The primary material may be distributed between a first active form (in which it is usable or active) and a second form in which it is inactive, inaccessible, or otherwise unavailable or unusable). The first active form of the primary material may be carried in solution, in suspension, in emulsion, or in colloidal suspension in the delivery fluid, so that it may be delivered from the delivery device along with the delivery fluid. In some embodiments, the second form may be an inactive form of the primary material, which may be carried in the delivery fluid along with the first active form. The second form may be carried in the delivery fluid in solution, in suspension, in emulsion, or in colloidal dispersion, for example.

In some such embodiments, the second form may be a chemically inactive form. This case is depicted inFIG. 6A, in which the first active form is indicated by reference number150, and the second (chemically inactive) form is indicated by reference number152. Delivery reservoir154, including outlet156and electromagnetically responsive control element158are also indicated. Both first active form150and second form152are carried in delivery fluid153.

In other embodiments, as illustrated inFIG. 6B, the second form160may include a chemically active form of the primary material162contained in a carrier structure164, while the first active form166is not contained in a carrier structure. The carrier structure may be, for example, a capsule, microcapsule, micelle, or fullerene, or other carrier structure known to those of skill in the relevant art. Delivery reservoir154includes outlet156and electromagnetically responsive control element168.

In still other embodiments, as illustrated inFIG. 6C, the second form176may be bound or associated with an interaction region178in the delivery reservoir154, while the first active form150is carried in delivery fluid153. Interaction of second form176with interaction region178may be controlled by electromagnetically responsive control element180.

As shown inFIG. 6D, in some embodiments, the second form186may be insoluble in the delivery fluid153; for example, the second form186may be precipitated out of the delivery fluid while first active form188is carried in delivery fluid153. As illustrated inFIG. 6D, the delivery reservoir154may include filter190located between the delivery reservoir154and the outlet156and configured for removing the second form186from the delivery fluid153. For example, openings192in filter190may be large enough to allow first form188to pass through, but too small to allow precipitated second form186to pass through the filter. In other embodiments, the filter may operate based upon increased affinity for the second form over the first active form, or other filtering principle, as is well known in the field of filtration. The term ‘filter’ is intended to encompass various types of materials-separating device.

The primary material may have a different immunogenicity, reactivity, stability, or activity when it is in the first active form than when it is in the second form. The primary material may be any of a wide variety of materials, including single materials or mixtures of materials. For example, the primary material may be a pharmaceutical material or a neutraceutical material. The primary material may be a biologically active material. In some embodiments, the primary material may include at least one nutrient, hormone, growth factor, medication, therapeutic compound, enzyme, genetic material, vaccine, vitamin, neurotransmitter, cytokine, cell-signaling material, pro- or anti-apoptotic agent, imaging agent, labeling agent, diagnostic compound, nanomaterial, inhibitor, or blocker. In some embodiments, the primary material may be a component or precursor of a biologically active material; for example, the primary material may include at least one precursor or component of a nutrient, hormone, growth factor, medication, therapeutic compound, enzyme, genetic material, vaccine, vitamin, neurotransmitter, cytokine, cell-signaling material, pro- or anti-apoptotic agent, imaging agent, labeling agent, diagnostic compound, nanomaterial, inhibitor, or blocker. Such precursors, may include, for example, prodrugs (see, e.g., “Liver-Targeted Drug Delivery Using HepDirect1 Prodrugs,” Erion et al., Journal of Pharmacology and Experimental Therapeutics Fast Forward, JPET 312:554-560, 2005 (first pub Aug. 31, 2004) and “LEAPT: Lectin-directed enzyme-activated prodrug therapy”, Robinson et al., PNAS Oct. 5, 2004 vol. 101, No. 40, 14527-14532, published online before print Sep. 24, 2004 (http://www.pnas.org/cgi/content/full/101/40/14527), both of which are incorporated herein by reference. Beneficial materials may be produced, for example, by conversion of pro-drug to drug, enzymatic reaction of material in bloodstream (CYP450, cholesterol metabolism, e.g., with cholesterol monooxygenase, cholesterol reductase, cholesterol oxidase). Depending on the intended application or use environment for the delivery device, the primary material may include at least one fertilizer, nutrient, remediation agent, antibiotic, microbicide, herbicide, fungicide, transfection agent, nanomaterial, disinfectant, metal salt, a material for adjusting a chemical composition or pH, such as buffer, acid, base, chelating agent, emulsifying agent, or surfactant. In some embodiments, the primary material may include a tissue-specific marker or targeting molecule, which may be, for example, a tissue-specific endothelial protein. A tissue-marker or targeting molecule may assist in targeting of the primary material to a specific location or tissue within a body of an organism.

The term “delivery fluid” as used herein, is intended to cover materials having any form that exhibits fluid or fluid-like behavior, including liquids, gases, powders or other solid particles in a liquid or gas carrier. The delivery fluid may be a solution, suspension, or emulsion.

Typically, the effective concentration of the primary material will be the concentration of the first active form of the primary material in the delivery fluid, which may differ from the total concentration of primary material in the delivery fluid, which is the combined concentration of both the first active and second forms of the primary material. The effective rate of delivery of primary material from the delivery device will generally equal the rate at which delivery fluid is pumped (or otherwise moves or is moved) out of the delivery reservoir multiplied by the effective concentration of primary material in the delivery fluid. A delivery device may include a pump for pumping delivery fluid from the delivery reservoir. Alternatively, in some cases the primary material may simply diffuse out of the delivery device. Various types of pumps may be used, without limitation. Suitable pumps may include, for example, osmotic, mechanical, displacement, centrifugal, and peristaltic pumps.

FIGS. 7A and 7Billustrate an embodiment of a delivery device that includes an osmotic pump. Delivery device250includes delivery reservoir252, which contains delivery fluid254and may have an outlet256. Electromagnetically responsive control element258is located in delivery reservoir252to control the distribution of primary material, which inFIG. 7Ais shown in the second (inactive, inaccessible or unusable) form260. Osmotic pump262includes osmotic chamber264containing osmotic pressure generating material266. Semi-permeable membrane268is permeable to osmotic fluid270but not to osmotic pressure generating material266. Osmotic fluid270thus flows into osmotic chamber264. This causes movable barrier274(which may be a rigid movable barrier or a flexible membrane) to move into delivery reservoir252, thus pumping delivery fluid254out of outlet256. As shown inFIG. 7B, activation of electromagnetically responsive control element258may cause primary material to be converted to first active form272.

The osmotic pressure-generating ability of the osmotic pressure-generating material may depend on the solubility of the osmotic pressure-generating material in the osmotic fluid, and/or upon the concentration of the osmotic pressure-generating material in the osmotic fluid, and varying either concentration or solubility may modify the osmotic-pressure generating ability of the osmotic pressure-generating material. Concentration of the osmotic pressure-generating material in the osmotic fluid may be modifiable by a change in solubility of the osmotic pressure-generating material in response to an electromagnetic field control signal or by a change in the osmotic fluid in response to an electromagnetic field control signal.

FIGS. 8A and 8Bdepict an embodiment of a delivery device300in which the electromagnetically responsive control element302includes an electromagnetic field responsive heating element that may respond to the control signal by producing heat. Primary material304is contained within delivery reservoir306in delivery fluid307. Electromagnetically responsive control element302may be located in the wall of delivery reservoir306. Electromagnetically responsive control element302has an initial temperature T1. Following heating of electromagnetically responsive control element302in response to an electromagnetic control signal, electromagnetically responsive control element302has a subsequent temperature T2, as shown inFIG. 8B. The change in temperature of electromagnetically responsive control element302may modify the concentration of primary material304within delivery reservoir306. InFIG. 8A, portion305of primary material304is insoluble, while inFIG. 8B, all of primary material304has gone into solution, due to the change in temperature of delivery fluid307. The electromagnetic field responsive control element302may include a ferrous, ferric, or ferromagnetic material, or other material with a significant electromagnetic “loss tangent” or resistivity. In the present example, the solubility of the primary material304in the delivery fluid307is depicted as increasing with increasing temperature, but in some embodiments, the solubility may decrease with increasing temperature. As in previously described embodiment, delivery device300may also include pump308and outlet310.

FIGS. 9A and 9Bdepict another embodiment of a delivery device350, in which the at least one electromagnetically responsive control element352may include an electromagnetic field responsive cooling element. The electromagnetic field responsive cooling element may be capable of producing a decrease in temperature in the delivery fluid, wherein the primary material354has a solubility in the delivery fluid356that changes in response to a decrease in temperature of the delivery fluid. The electromagnetic field responsive cooling element352may include a thermoelectric element, for example. Methods and/or mechanisms of producing cooling may include, but are not limited to, thermoelectric (Peltier Effect) and liquid-gas-vaporization (Joule-Thomson) devices, or devices which employ “phase-changing” materials or systems involving significant enthalpies of transition. The solubility of the primary material354may increase with decreasing temperature, or it may decrease with decreasing temperature, as depicted inFIGS. 9A and 9B. InFIG. 9A, for example, cooling element352is not producing cooling, and the temperature is at a higher temperature T1and primary material354is substantially all in solution in delivery fluid356. InFIG. 9B, cooling element352may be activated to produce cooling, so that the temperature of delivery fluid356decreases to temperature T2. At temperature T2a portion358or primary material goes out of solution, resulting in a lower effective concentration of primary material in delivery fluid356.

In some embodiments of the delivery device, the at least one electromagnetically responsive control element may be a shape-changing structure that changes in at least one dimension in response to an electromagnetic control signal.FIGS. 10A and 10Bdepict delivery device400that includes an electromagnetically responsive control element402that is a shape-changing structure located in the wall of delivery reservoir404. An interaction region406including interaction sites408may be located on or adjacent to electromagnetically responsive control element402, so that the dimension of interaction region406is modified with the change in dimension of electromagnetically responsive control element402. Interaction sites408may bind primary material410, thus keeping it out of solution, and maintaining a lower effective concentration in delivery reservoir404; a change in spacing or exposure of interaction sites408may modify the interaction of primary material410with interaction sites408, and thus modifies the effective concentration in delivery reservoir404. For example, inFIG. 10B, the electromagnetically responsive control element402′ has contracted in at least one dimension to produce a corresponding decrease in size of interaction region406, and reduction in spacing between interaction sites408. In the example depicted inFIG. 10B, the reduction in interaction site spacing reduces interactions with primary material410, causing it to go into solution in delivery fluid412in higher concentration.

Interaction sites may be localized to an interaction region, as depicted inFIGS. 10A and 10B, or, in alternative embodiments, the interaction sites may be distributed to various locations within the delivery reservoir. The delivery device may include a plurality of interaction sites for the primary material within the delivery reservoir, the likelihood of interaction of the primary material with the interaction sites controllable by the electromagnetic field control signal, wherein interaction of the primary material with the interaction sites causes a change in effective concentration within the delivery reservoir. The interaction sites may be capable of interacting with the primary material by one or more of binding, reacting, interacting, or forming a complex with the primary material. The interaction sites may be responsive to an electromagnetic field control signal by a change in at least one characteristic, the change in the at least one characteristic modifying the interaction between the interaction sites and the primary material. The at least one characteristic may include, but is not limited to, at least one of a solubility, a reactivity, a distribution within the delivery reservoir, a density, a temperature, a conformation, an orientation, an alignment, or chemical potential, for example.

In some embodiments, the at least one electromagnetically responsive control element may be an electromagnetic field responsive molecule in the delivery fluid, and wherein the electromagnetic field responsive molecule undergoes a change in conformation from a first conformation state to a second conformation state in response to the electromagnetic control signal, and wherein the first conformation state has a first solubility in the delivery fluid and wherein the second conformation state has a second solubility in the delivery fluid. Such an electromagnetic field responsive molecule may form at least a portion of the primary material in the delivery fluid, or alternatively, the electromagnetic field responsive molecule may form at least a portion of a secondary material that influences the solubility of the primary material in the delivery fluid, as illustrated inFIGS. 11A and 11B.

FIG. 11Adepicts a delivery device420including delivery reservoir422and pump424. Delivery reservoir422contains delivery fluid425, primary material426, and secondary material428. Delivery fluid424may exit delivery reservoir422via outlet430. InFIG. 11A, secondary material428is all in solution, and a portion432of primary material has been forced out of solution. InFIG. 11B, in response to a change in the electromagnetic field control signal, a portion434of secondary material428has gone out of solution, with the effect that a larger amount of primary material426goes into solution, thus increasing the concentration of primary material426in delivery fluid242. Secondary material428may influence the concentration of primary material426by modifying the pH, polarity or other characteristic of delivery fluid244, or by interacting or reacting with primary material426directly to modify its solubility in delivery fluid424.

FIGS. 10A and 10Bdepict one method of using a shape changing material to vary the effective concentration of a primary material in a delivery device. Other embodiments that utilize shape-changing materials are also contemplated. A shape-changing structure may include a polymeric material, a ferropolymer, a hydrogel, a bimetallic structure, or a shape memory material. In some embodiments, the shape-changing structure may be an expanding or contracting structure, wherein the change in at least one dimension includes an expansion or contraction in at least one dimension. Expansion or contraction of the expanding or contracting structure may modify the volume of a delivery reservoir, or expose molecular structures to the delivery fluid that modify the solubility of the primary material in the delivery fluid, as will be discussed in the following example.

A change in surface area may be produced by stretching a portion of the delivery reservoir, as depicted inFIGS. 12A-12D, or a change in surface area may be produced by unfolding a portion of the delivery reservoir, as depicted inFIGS. 13A and 13B, or by some of change in conformation of at least a portion of the delivery reservoir.

FIGS. 12A-12Ddepict the effect of changes in one or two dimensions on an interaction region450. Such an interaction region may be formed, for example, on an electromagnetically responsive control element that expands in response to a control signal. Interaction region450may include a plurality of reaction sites452, and having initial length of x1in a first dimension and y1in a second dimension.FIG. 12Bdepicts interaction region450following a change in the first dimension, to a length x2.FIG. 12Cdepicts interaction region450following a change in the second dimension, to a length y2, andFIG. 12Ddepicts interaction region450following a change in both the first and second dimensions, to a size of x2by y2. In each case, a change in dimension results in a change in distance between reaction sites452. The dimension change depicted inFIGS. 12A-12Dmay be viewed as a ‘stretching’ or ‘expansion’ of the interaction region. Increasing the surface area of the interaction region may increase the rate of the reaction. Increasing the surface area of the interaction region (e.g., by stretching the surface) may increase the distance between reaction sites on the interaction region. An increased distance between reaction sites may lead to an increase in reaction rate (for example, in cases where smaller spacing between reaction sites leads to steric hindrance that blocks access of reactants to reaction sites).

In addition to increasing surface areas or reaction volumes, expansion of an electromagnetically responsive control element may also have the effect of exposing additional portions of an interaction region or exposing additional functional group to influence a reaction condition. Increasing the surface area of the interaction region by unfolding or other forms of ‘opening’ of the interaction region structure of at least a portion of the reaction area may increase the number of reaction sites on the interaction region (e.g. by exposing additional reaction sites that were fully or partially hidden or obstructed when the interaction region was in a folded configuration). For example, the area of an interaction region may be increased by the unfolding of at least a portion of the reaction area to expose additional portions of the reaction area, as depicted inFIGS. 13A and 13B. InFIG. 13A, an interaction region500, which includes or is made up of an electromagnetically responsive control element, can be expanded by unfolding to the form depicted inFIG. 13B. Interaction region500has a pleated structure that includes ridges502a-502eand valleys504a-504d. Reaction sites506may be located in or on ridges502a-502eand valleys504a-504d. In the folded form illustrated inFIG. 13A, reaction sites506located in valleys504a-504dare ‘hidden’ in the sense that reactants may not fit into the narrow valleys to approach those reaction sites, while reaction sites on ridges502a-502eremain exposed. When interaction region500is unfolded to the form shown inFIG. 13B, reaction sites506in valleys504a-506dare exposed, because the open valleys permit access of reactants to the reaction sites in the valleys. Examples of materials that unfold in response to electromagnetic fields include ionic polymer-metal composites (IPMC) as described in Shahinpoor et al., “Artificial Muscle Research Institute: Paper: Ionic Polymer-Metal Composites (IPMC) As Biomimetic Sensors, Actuators and Artificial Muscles-A Review”; University of New Mexico; printed on Oct. 21, 2005; pp. 1-28; located at: http://www.unm.edu/˜amri/paper.htm1, which is incorporated herein by reference.

Increasing the surface area of the interaction region may decrease the rate of the interaction in some circumstances and increase the rate of interaction in others. Exposure of additional portions of the interaction region may expose additional functional groups that are not reaction sites, but that may produce some local modification to a surface property of the interaction region that in turn modifies the rate or kinetics of the reaction. For example, exposed functional groups may produce at least a local change in pH, surface energy, or surface charge. See, for example, U.S. patent publication 2003/0142901 A1, which is incorporated herein by reference. A related modification of the interaction region may include an increase in porosity or decrease in density of an electromagnetically responsive control element. An increase in porosity may have a similar effect to unfolding with respect to modifying the spacing or exposure of reaction sites, functional groups, etc. See, for example U.S. Pat. Nos. 5,643,246, 5,830,207, and 6,755,621, all of which are incorporated herein by reference.FIGS. 14A and 14Bdepict an electromagnetically responsive control element530that expands in response to an electromagnetic control signal, with a corresponding increase in size of pores532inFIG. 14Brelative to the size of pores532inFIG. 14A.

A change in the spacing of interaction sites may increase or decrease the rate of interaction, or modify another parameter of an interaction, in a manner that depends on the specific reaction and reactants. Heating or cooling of a reaction volume may also modify a chemical reaction by modifying the pressure or the pH or the osmolality or other reaction-pertinent chemical variables within the reaction space. In some embodiments, a delivery device may include at least one interaction region capable of interacting with the primary material by one or more of binding, reacting, interacting, or forming a complex with the primary material. The at least one interaction region may be responsive to the electromagnetic control signal by a change in at least one characteristic, the change in the at least one characteristic modifying the interaction between the at least one interaction region and the primary material. For example, the at least one characteristic may include at least one solubility, reactivity, temperature, conformation, orientation, alignment, binding affinity, chemical potential, surface energy, porosity, osmolality, pH, distribution within the delivery reservoir, or density. In some embodiments, at least a portion of the delivery reservoir containing the at least one interaction region may be responsive to an electromagnetic control signal by a change in the surface area of the portion of the delivery reservoir, the change in surface area modifying the likelihood of interaction of the primary material with the at least one interaction region. For example, the change of surface area may be produced by stretching or expansion of the portion of the delivery reservoir, or by unfolding of the portion of the delivery reservoir.

The influence of modifying the surface area of an interaction region is described further in connection withFIGS. 15A and 15Band16A and16B.FIGS. 15A and 15Billustrate how an increase of the surface area of an interaction region by stretching or expansion may increase the rate of the interaction occurring at the interaction region. Multiple interaction sites552are located in interaction region550. As shown inFIG. 15A, prior to stretch or expansion, interaction sites552are close together, and primary material554, which binds to the interaction sites552, is sufficiently large that it is not possible for reactant554to bind to each interaction site552. When interaction region550has been stretched or expanded to expanded form550′ as depicted inFIG. 15B, so that the interaction sites552are further apart, it is possible for primary material554to bind to a larger percentage of the interaction sites, thus increasing the rate of interaction.

In some embodiments, an increase in the surface area of the interaction region by stretching or expansion may decrease the interaction rate (for example, in cases where a particular spacing is needed to permit binding or association of primary material with several interaction sites simultaneously).FIGS. 16A and 16Billustrate how an increase in the surface area of an interaction region570by stretching or expansion may decrease the rate of the interaction occurring at the interaction region. Again, multiple interaction sites572and574are located in the interaction region570, as depicted inFIG. 16A. In the present example binding of a primary material576to interaction region570requires binding of a primary material576to two interaction sites572and574. When interaction region570is stretched or expanded to expanded form570′ as depicted inFIG. 16B, the spacing of the two interaction sites572and574is changed so that primary material576does not readily bind to interaction region in the expanded form570′, thus reducing the rate of interaction.

Many materials expand when thermal energy is applied. By combining materials as in polymer gels one can use the differing properties of individual components to affect the whole. Thermally-responsive materials include thermally responsive gels (hydrogels) such as thermosensitive N-alkyl acrylamide polymers, Poly(N-isopropylacrylamide) (PNIPAAm), biopolymers, crosslinked elastin-based networks, materials that undergo thermally triggered hydrogelation, memory foam, resin composites, thermochromic materials, proteins, memory shape alloys, plastics, and thermoplastics. Materials that contract or fold in response to heating may include thermally-responsive gels (hydrogels) that undergo thermally triggered hydrogelation (e.g. Polaxamers, uncross-linked PNIPAAm derivatives, chitosan/glycerol formulations, elastin-based polymers), thermosetting resins (e.g. phenolic, melamine, urea and polyester resins), dental composites (e.g. monomethylacrylates), and thermoplastics.

Some examples of reactions that may be sped up by change in distance between reaction sites include those involving drugs designed with spacers, such as dual function molecules, biomolecules linked to transition metal complexes as described in Paschke et al, “Biomolecules linked to transition metal complexes—new chances for chemotherapy”; Current Medicinal Chemistry; bearing dates of October 2003 and Oct. 18, 2005, printed on Oct. 24, 2005; pp. 2033-44 (pp. 1-2); Volume 10, Number 19; PubMed; located at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1 2871101&dopt=Abstract, and Schiff bases as described in Puccetti et al., “Carbonic anhydrase inhibitors”, Bioorg. Med. Chem. Lett. 2005 Jun. 15; 15(12): 3096-101 (Abstract only), both of which are incorporated herein by reference. Other reactions include reactions responding to conformational (allosteric) changes including regulation by allosteric modulators, and reactions involving substrate or ligand cooperativity in multiple-site proteins, where binding affects the affinity of subsequent binding, e.g., binding of a first O2molecule to Heme increases the binding affinity of the next such molecule, or influence of Tau on Taxol, as described in Ross et al., “Tau induces cooperative Taxol binding to microtubules”; PNAS; Bearing dates of Aug. 31, 2004 and 2004; pp. 12910-12915; Volume 101, Number 35; The National Academy of Sciences of the USA; located at: http://gabriel.physics.ucsb.edu/˜deborah/pub/RossPNASv101p12910y04.pdf, which is incorporated herein by reference. Reactions or interactions that may be slowed down by increased reaction site spacing include reactions responsive to conformational (allosteric) changes, influence or pH, or crosslinking. See for example Boniface et al., “Evidence for a Conformational Change in a Class II Major Histocompatibility Complex Molecule Occuring in the Same pH Range Where Antigen Binding Is Enhanced”; J. Exp. Med.; Bearing dates of January 1996 and Jun. 26, 2005; pp. 119-126; Volume 183; The Rockefeller University Press; located at: http://wwwjem.org also incorporated herein by reference or Sridhar et al., “New bivalent PKC ligands linked by a carbon spacer: enhancement in binding affinity”; J Med Chem.; Bearing dates of Sep. 11, 2003 and Oct. 18, 2005, printed on Oct. 24, 2005; pp. 4196-204 (pp. 1-2); Volume 46, Number 19; PubMed (Abstract); Located at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1 2954072&dopt=Abstract, also incorporated herein by reference.

In some embodiments, the interaction region may include interaction sites that include a secondary material capable of interacting with or influencing the solubility of the primary material. The electromagnetically responsive control element may modify the influence of the secondary material. In some embodiments the secondary material may not be localized to an interaction region, but may be distributed within the delivery reservoir, but responsive to an electromagnetic control signal. The secondary material may interact with or influence primary material in a variety of ways. As a first example, the secondary material may be a receptor or other binding location that binds or sequesters the primary material, either specifically or non-specifically, to take it out of solution.FIGS. 17A and 17Bdepict an interaction between primary material600and secondary material602in interaction region604. InFIG. 17A, prior to activation of electromagnetically responsive control element606, primary material600does not bind to secondary material602in interaction region604. Following activation of electromagnetically responsive control element606, secondary material602undergoes a change to modified form602′ as depicted inFIG. 17B, which allows primary material600to bind to it and go out of solution, thus reducing the effective concentration of the primary material in the delivery fluid.

In the example shown inFIGS. 18A and 18B, secondary material630is not itself a receptor or binding site for the primary material632, but modifies interaction between the primary material632and an interaction site634(which may be, for example, a binding or receptor site) in interaction region636. InFIG. 18A, the secondary material630is in a first configuration which blocks access of primary material632to interaction site634. InFIG. 18B, under the influence of electromagnetically responsive control element638, secondary material630has assumed a second configuration630′ which permits access of primary material632to interaction site634. Secondary material630may be a material that modifies the rate or nature of the interaction between primary material632and interaction site634in response to an electromagnetic control signal by steric effects, by modifying the polarity of at least a portion of an interaction region, such as e.g., hydrophobic or hydrophilic groups; by modifying the pH of at least a portion of the interaction region, with acids or acidifiers (e.g., ammonium chloride), bases or alkalizers (sodium bicarbonate, sodium acetate) or buffering agents (e.g., mono- or di-hydrogen phosphates); or it may be a material that modifies the charge of at least a portion of the interaction region, such as including various enzyme, neuraminidase, transferase, antioxidants, and charge donors.

In the example ofFIGS. 19A and 19B, secondary material640is a reactant that reacts with primary material642to produce reaction product644. Primary material642approaches secondary material640in interaction region646inFIG. 19A, and reaction product644leaves interaction region646inFIG. 19B. The reaction between secondary material640and primary material642is caused, produced, facilitated, or otherwise increased or enhanced by activation of electromagnetically responsive control element648, (e.g., to produce heating, cooling, a change in surface charge, conformation, etc.) Reaction product646may have a different effective concentration in the delivery fluid than primary material642due to different solubility, or chemical activity, for example, or because the reaction results in an increase or decrease in the number of chemically active molecules in the reaction chamber. A reaction by-product610may remain at interaction region646, as depicted inFIG. 19B, or secondary material640may be completely consumed by the reaction.

The influence of the electromagnetically responsive control element in the examples depicted inFIGS. 17A-19Bmay be any of various influences, including but not limited to those described herein; e.g., modifying the temperature of the interaction region or exposing reaction sites or functional groups. The interaction that takes place at the interaction region may change the effective concentration of primary material within the delivery reservoir by producing reaction products in different quantities or with different solubility or chemical activity than the reactants. In some embodiments, the interaction region may include a catalyst that facilitates a chemical reaction but is not modified by the chemical reaction, for example, metals such as platinum, acid-base catalysts, catalytic nucleic acids such as ribozymes or DNAzymes. The interaction region may include an enzyme, such as an oxidoreductase (e.g. glucose oxidase), transferase (including glycosyltransferase, kinase/phosphorylase), hydrolase, lyase, isomerase, ligase, and enzymatic complexes and/or cofactors. Various examples of catalysts are provided in Kozhevnikov, “Catalysts for Fine Chemical Synthesis, Volume 2, Catalysis by Polyoxometalates”; Chipsbooks.com; Bearing dates of 2002 and 1998-2006, printed on Oct. 21, 2005; pp 1-3 (201 pages); Volume 2; Culinary and Hospitality Industry Publications Services; located at: http://www.chipsbooks.com/catcem2.htm, which is incorporated herein by reference.

Modifying a reaction condition at the interaction region may also be accomplished by heating or cooling at least a portion of the interaction region, or by modifying the osmolality or pH, surface charge, or surface energy of at least a portion of the interaction region. Similarly, modifying a reaction condition at the interaction region may include modifying a parameter of a reaction space within the delivery device, the reaction space containing the interaction region, e.g. by modifying the volume of the reaction space, heating or cooling at least a portion of the reaction space, or modifying the osmolality, pH, pressure, temperature, chemical composition, or chemical activity of at least a portion of the reaction space.

In some embodiments, expansion or other conformation change of an electromagnetically responsive control element may produce other modifications to a condition in the delivery reservoir. For example, a volume of a delivery reservoir containing the interaction region may be increased by expansion of an electromagnetically responsive control element, as depicted inFIGS. 20A and 20B. Delivery device650includes delivery reservoir652containing primary material654and delivery fluid656and having a first volume as shown inFIG. 20A. An electromagnetically responsive control element658that changes dimension in response to an electromagnetic control signal forms an expandable portion of the wall of delivery reservoir652. Upon expansion of electromagnetically responsive control element to expanded form658′ shown inFIG. 20B, the volume of delivery reservoir652is increased, and the concentration of primary material654within delivery reservoir652is thus decreased. In this and other embodiments, the delivery device may include at least one sensor660for detecting at least one parameter from the delivery reservoir. For example, the sensor may detect a quantity or concentration of primary material in the delivery reservoir. In other embodiments, the delivery device may include at least one sensor for detecting a concentration or activity of a chemical within at least a portion of an environment surrounding the delivery device. Examples of sensors are described in, U.S. Pat. No. 6,935,165, and U.S. Patent Publication 2004/0007051, both of which are incorporated herein by reference.

FIG. 21depicts in schematic form an embodiment of a delivery device700including an electromagnetically responsive control element702that includes an active portion704and a power receiving structure706. Delivery device also includes delivery reservoir708and outlet710. Power receiving structure706may be any structure that has a size, shape, and material that is suitable for receiving and transducing electromagnetic energy of a particular frequency or frequency band. The power receiving structure may include an antenna. The power receiving structure may include a resonant structure. The resonant structure may be a resonant circuit, a molecular bond, or a mechanically resonant structure. In some embodiments, power receiving structure706may be highly frequency-selective, while in other embodiments it may react usefully over a wide frequency band, or over multiple frequency bands. Power receiving structure706may be formed of various metallic or electrically or magnetically active materials. Active portion704may include various materials that respond mechanically, thermally or chemically to electromagnetic energy received and transduced by power receiving structure706to influence the effective concentration of primary material in delivery reservoir.

FIG. 22depicts an embodiment of a delivery device750including an RFID752. Delivery device750includes delivery reservoir754, outlet756and electromagnetically responsive control element758. RFID752may store a unique identification code that allows delivery device750to be identified by a remote controller (not shown) that includes RFID detection circuitry. This provides for selective control of particular delivery devices, for example.

Delivery devices as described herein may be configured for use in a variety of environments. A delivery device of the type disclosed herein may include a body structure (e.g., body structure38inFIGS. 2 and 3) adapted for positioning in an environment selected from a body of an organism, as depicted inFIG. 1, or a body of water, or a contained fluid volume. The delivery reservoir may be located within the body structure. The body structure adapted for positioning in a contained fluid volume selected from an industrial fluid volume, an agricultural fluid volume, a swimming pool, an aquarium, a drinking water supply, a potable water supply, and an HVAC system cooling water supply.

Various embodiments may be used in connection with selected biomedical applications (e.g., with delivery devices adapted for placement in the body of a human or other animal). It is also contemplated that delivery systems as described herein may be used in a variety of environments, not limited to the bodies of humans or other animals. Delivery devices may be placed in other types of living organisms (e.g., plants). The environments for use of embodiments described herein are merely exemplary, and the delivery systems as disclosed herein are not limited to use in the applications presented in the examples.

FIG. 23illustrates an exemplary embodiment of a delivery system770in which a delivery device772is located in a small enclosed fluid volume774(e.g., an aquarium). A remote controller776is located outside enclosed fluid volume774.

FIG. 24illustrates a further exemplary embodiment of a delivery system780in which a delivery device782is located in a larger enclosed fluid volume784(which may be, for example, a water storage tank, an HVAC system cooling water tank, a tank containing an industrial fluid or an agricultural fluid). A remote controller786is located outside enclosed fluid volume784.

FIG. 25illustrates a further exemplary embodiment of a delivery system790in which a delivery device792is located in a body of water794(a lake or pond is depicted here, but such delivery systems may also be designed for use in rivers, streams, or oceans). A remote controller796is shown located outside of body of water794, though in some embodiments it may be advantageous to place remote controller796at a location within body of water794.

The body structure of the delivery device may be adapted for a specific environment. The size, shape, and materials of the body structure influence suitability for a particular environment. For example, a device intended for use in a body of a human or other organism would typically have suitable biocompatibility characteristics. For use in any environment, the body structure (and device as a whole) may be designed to withstand environmental conditions such as temperature, chemical exposure, and mechanical stresses. Moreover, the body structure may include features that allow it to be placed or positioned in a desired location in the environment, or targeted to a desired location in the environment. Such features may include size and shape features, tethers or gripping structures to prevent movement of the body structure in the environment (in the case that the device is placed in the desired location) or targeting features (surface chemistry, shape, etc.) that may direct the device toward or cause it to be localized in a desired location. The body structure may include a tissue-specific marker or targeting molecule. For example, the tissue specific marker or targeting molecule may be a tissue specific endothelial protein. Small devices (e.g. as may be used for placement in the body of an organism) may be constructed using methods known to those in skill of the art of microfabrication. In applications where size is not a constraint, a wide variety of fabrication methods may be employed. The body structure of the delivery device may be formed from various materials or combinations of materials, including but not limited to plastics and other polymers, ceramics, metals, and glasses, and by a variety of manufacturing techniques.

In some embodiments, the delivery device may be a MEMS device or other microfabricated device. The delivery device may be constructed from at least one polymer, ceramic, glass, or semiconductor material. In some embodiments, the delivery device may be a battery-free device, powered by power beaming, inductive coupling, or an environmental power source. In still other embodiments, the device may include a battery or other on-board power source. In some embodiments, the delivery device may include an electromagnetic control signal generator, which may be located substantially in, on or adjacent to the delivery reservoir. In other embodiments, the electromagnetic control signal generator may be located at a location remote from the delivery reservoir.

As discussed herein, a remote controller for a delivery device may include an electromagnetic signal generator capable of producing an electromagnetic signal sufficient to activate an electromagnetically responsive control element of a delivery device located in an environment to change a concentration of a primary material within a delivery reservoir of the delivery device; and an electromagnetic signal transmitter capable of wirelessly transmitting the electromagnetic signal to the electromagnetically responsive control element. Various types and frequencies of electromagnetic control signals may be used in delivery systems as described herein. For example, in some embodiments, the delivery system may include a remote controller configured to generate a static or quasi-static electrical field control signal or static or quasi-static magnetic field control sufficient to activate the electromagnetically responsive control element to control the effective concentration of primary material in a desired manner. In other embodiments, the remote controller may be configured to generate a radio-frequency, microwave, infrared, millimeter wave, optical, or ultraviolet electromagnetic field control signal sufficient to activate the electromagnetically responsive control element to control the effective concentration of primary material in a desired manner.

The electromagnetic control signal may be produced based at least in part upon a predetermined activation pattern. As shown inFIG. 26, a predetermined activation pattern may include a set of stored data1002a,1002b,1002c,1002d, . . .1002e, having values f(t1), f(t2), f(t3), f(t4), . . . f(tN), stored in a memory location1000. The activation pattern upon which the electromagnetic signal is based is depicted in plot1004inFIG. 26. In plot1004, time tnis indicated on axis1006and signal amplitude f(tn), which is a function of tn, is indicated on axis1008. The value of the electromagnetic signal over time is represented by trace1010. The predetermined activation pattern represented by data1002a,1002b,1002c,1002d, . . .1002emay be based upon calculation, measurements, or any other method that may be used for producing an activation pattern suitable for activating an electromagnetically responsive control element. Memory1000may be a memory location in a remote controller. As an example, a simple remote controller may include a stored activation pattern in memory and include electrical circuitry configured to generate an electromagnetic control signal according to the pattern for a preset duration or at preset intervals, without further input of either feedback information or user data. In a more complex embodiment, a predetermined activation pattern may be generated in response to certain feedback or user input conditions.

In some embodiments, an electromagnetic signal may be produced based upon a model-based calculation. As shown inFIG. 27, an activation pattern f(tn) may be a function not only of time (tn) but also of model parameters P1, P2, . . . Pk, as indicated by equation1050. Data1052a,1052b, . . .1052chaving values P1, P2, . . . Pkmay be stored in memory1054. An electromagnetic control signal may be computed from the stored model parameters and time information. For example, as indicated in plot1056, time is indicated on axis1058and the strength or amplitude of the electromagnetic control signal is indicated on axis1060, so that trace1061represents f(tn). Memory1054may be a memory location in a remote controller. The remote controller may generate an electromagnetic control signal based upon the stored function and corresponding parameters. In some embodiments, the electromagnetic control signal may also be a function of one or more feedback signals (from the delivery device or the environment, for example) or of some user input of data or instructions.

FIG. 28depicts a remote controller1100having a memory1104capable of storing pre-determined data values or parameters used in model-based calculation, as described in connection withFIGS. 29 and 30. Remote controller1100may also include electrical circuitry1102, signal generator1112, and signal transmitter1114for transmitting electromagnetic control signal1116. Memory1104may include memory location1106for containing a stored activation pattern or model parameters; portions of memory1104may also be used for storing operating system, program code, etc. for use by processor1102. The controller1100may also include a beam director1118, such as an antenna, optical element, mirror, transducer, or other structure that may impact control of electromagnetic signaling. The electrical circuitry may include any or all of analog circuitry, digital circuitry, one or more microprocessors, computing devices, memory devices, and so forth. Remote controller may include at least one of hardware, firmware, or software configured to control generation of the electromagnetic control field signal. Software may include, for example, instructions for controlling the generation of the electromagnetic control signal and instructions for controlling the transmission of the electromagnetic control signal to the electromagnetically responsive control element.

Remote controller1100may be configured to produce an electromagnetic control signal having various characteristics, depending upon the intended application of the system. Design specifics of electrical circuitry, signal generator, and signal transmitter will depend upon the type of electromagnetic control signal. The design of circuitry and related structures for generation and transmission of electromagnetic signals can be implemented using tools and techniques known to those of skill in the electronic arts. See, for example, Electrodynamics of Continuous Media, 2nd Edition, by L. D. Landau, E. M. Lifshitz and L. P. Pitaevskii, Elsevier Butterworth-Heinemann, Oxford, especially but not exclusively pp. 1-13- and 199-222, which is incorporated herein by reference, for discussion of theory underlying the generation and propagation of electrical, magnetic, and electromagnetic signals.

Remote controller1100may be configured to produce an electromagnetic control signal having various characteristics, depending upon the intended application of the system. In some embodiments, a specific remote controller may be configured to produce only a specific type of signal (e.g., of a specific frequency or frequency band) while in other embodiments, a specific remote controller may be adjustable to produce a signal having variable frequency content. Signals may include components which contribute a DC bias or offset in some cases, as well as AC frequency components.

Generation of radio frequency electromagnetic signals is described, for example, in The ARRL Handbook for Radio Communications 2006, R. Dean Straw, Editor, published by ARRL, Newington, Conn., which is incorporated herein by reference. Electromagnetic signal generator1112may be capable of producing an electromagnetic control signal sufficient to activate an electromagnetically responsive control element of a delivery device located in an environment to change an effective concentration of a primary material in a delivery fluid within a fluid-containing structure of the delivery device; and an electromagnetic signal transmitter capable of wirelessly transmitting the electromagnetic control signal to the electromagnetically responsive control element of a delivery device in an environment. Signal transmitter1114may include a sending device which may be, for example, an antenna or waveguide suitable for use with an electromagnetic signal. Static and quasistatic electrical fields may be produced, for example, by charged metallic surfaces, while static and quasistatic magnetic fields may be produced, for example, by passing current through one or more wires or coils, or through the use of one or more permanent magnets, as known to those of skill in the art. As used herein, the terms transmit, transmitter, and transmission are not limited to only transmitting in the sense of radiowave transmission and reception of electromagnetic signals, but are also applied to wireless coupling and/or conveyance of magnetic signals from one or more initial locations to one or more remote locations.

The remote controller may be modified as appropriate for its intended use. For example, it may be configured to be wearable on the body of a human (or other organism) in which a delivery device has been deployed, for example on a belt, bracelet or pendant, or taped or otherwise adhered to the body of the human. Alternatively, it may be configured to be placed in the surroundings of the organism, e.g., as a table-top device for use in a home or clinical setting.

In various embodiments, the delivery device may include a remote controller configured to generate a static or quasi-static electrical field control signal, a static or quasi-static magnetic field control signal, a radio-frequency electromagnetic control signal, a microwave electromagnetic control signal, an infrared electromagnetic control signal, a millimeter wave electromagnetic control signal, an optical electromagnetic control signal, or an ultraviolet electromagnetic control signal sufficient to activate the electromagnetically responsive control element to control the effective concentration of the primary material in the delivery fluid.

Various types of electromagnetic field control signals may be used to activate the electromagnetically responsive control element. The electromagnetically responsive control element may be responsive to a static or quasi-static electrical field or a static or quasi-static magnetic field. It may be responsive to various types of non-ionizing electromagnetic radiation, or in some cases, ionizing electromagnetic radiation. Electromagnetic field control signals that may be used in various embodiments include radio-frequency electromagnetic radiation, microwave electromagnetic radiation, infrared electromagnetic radiation, millimeter wave electromagnetic radiation, optical electromagnetic radiation, or ultraviolet electromagnetic radiation.

The electromagnetic signal generator may include electrical circuitry and/or a microprocessor. In some embodiments, the electromagnetic signal may be produced at least in part according to a pre-determined activation pattern. The remote controller may include a memory capable of storing the pre-determined activation pattern. In some embodiments, the electromagnetic signal may be produced based on a model-based calculation; the remote controller may include a memory capable of storing model parameters used in the model-based calculation.

In some embodiments, the remote controller may produce an electromagnetic signal having one or both of a defined magnetic field strength or defined electric field strength. In general, the term field strength, as applied to either magnetic or electric fields, may refer to field amplitude, squared-amplitude, or time-averaged squared-amplitude. The electromagnetic signal may have signal characteristics sufficient to produce a change in dimension of the electromagnetically responsive control element, a change in temperature of the electromagnetically responsive control element, a change in conformation of the electromagnetically responsive control element, or a change in orientation or position of the electromagnetically responsive control element. In some embodiments, the electromagnetic signal generator may include an electromagnet or electrically-polarizable element, or at least one permanent magnet or electret. The electromagnetic signal may be produced at least in part according to a pre-programmed pattern. The electromagnetic signal may have signal characteristics sufficient to produce a change in dimension in the electromagnetically responsive control element, the change in dimension causing a change in the concentration of the primary material within the delivery reservoir of the delivery device. It may have signal characteristics sufficient to produce a change in temperature of the electromagnetically responsive control element, the change in temperature causing a change in the concentration of the primary material within the delivery reservoir of the delivery device. In some embodiments, it may have signal characteristics sufficient to produce a change in one or more of shape, volume, surface area or configuration of the electromagnetically responsive control element, the change in dimension in one or more of shape, volume, surface area or configuration of the electromagnetically responsive control element causing a change in the concentration of the primary material within the delivery reservoir of the delivery device. The electromagnetic signal may have signal characteristics sufficient to produce a change in shape in an electromagnetically responsive control element including a shape memory material, a bimetallic structure, or a polymeric material. The electromagnetic signal may have a defined magnetic field strength or spatial orientation, or a defined electric field strength or spatial orientation.

In some embodiments, the remote controller may be configured to generate and transmit an electromagnetic control signal having at least one of frequency and orientation that are selectively receivable by the at least one magnetically responsive control element. In some embodiments, the remote controller may include at least one of hardware, software, or firmware configured to perform encryption of electromagnetic control signal to produce an encrypted electromagnetic control signal.

FIG. 29depicts an example of an electromagnetic waveform of a type that may be used to activate and electromagnetically responsive control element. In plot1150, time is plotted on axis1152, and electromagnetic field strength is plotted on axis1154. Trace1156has the form of a square wave, switching between zero amplitude and a non-zero amplitude, A.

FIG. 30depicts another example of an electromagnetic waveform. In plot1200, time is plotted on axis1202, and electromagnetic field strength is plotted on axis1204. Trace1206includes bursts1208and1210, during which the field strength varies between A and −A, at a selected frequency, and interval1212, during which field strength is zero.

FIG. 31depicts another example of an electromagnetic waveform. In plot1250, time is plotted on axis1252, and electromagnetic field strength is plotted on axis1254. Trace1256includes bursts1258, and1262, during which the field strength varies between A and −A at a first frequency, and burst1260, during which the field strength varies between B and −B at a second (lower) frequency. Different frequencies may be selectively received by certain individuals or classes of electromagnetically responsive control elements within a device or system including multiple electromagnetically responsive control elements. An electromagnetic control signal may be characterized by one or more frequencies, phases, amplitudes, or polarizations. An electromagnetic control signal may have a characteristic temporal profile and direction, and characteristic spatial dependencies.

The magnetic or electric field control signal produced by the remote controller may have one or both of a defined magnetic field strength or a defined electric field strength. At low frequencies the electrical and magnetic components of an electromagnetic field are separable when the field enters a medium. Therefore, in static and quasi-static field application, the electromagnetic field control signal may be considered as an electrical field or a magnetic field. A quasi-static field is one that varies slowly, i.e., with a wavelength that is long with respect to the physical scale of interest or a frequency that is low compared to the characteristic response frequency of the object or medium; therefore, the frequency beyond which a field will no longer be considered ‘quasi-static’ is dependent upon the dimensions or electrodynamic properties of the medium or structure(s) influenced by the field.

As depicted in various embodiments, e.g., as shown inFIGS. 6A-10B, the delivery reservoir may include an outlet through which the delivery fluid moves into an environment, for example by pumping or diffusion. In other embodiments, as depicted inFIG. 32, a delivery system1300may include a downstream fluid handling structure1302in fluid communication with the delivery reservoir1304and configured to receive fluid1306ejected from the delivery reservoir1304in response to the change in at least one of pressure or volume in the delivery reservoir1304. The downstream fluid handling structure1302may include a chamber, as depicted inFIG. 32. Delivery device1300may also include a pump (e.g., and osmotic pump1308) and an electromagnetically responsive control element1310.

In other embodiments, e.g. delivery device1350shown inFIG. 33, a downstream fluid handling structure1352may include one or more channels1354, chambers1356, splitters1358, mixers1360, or other fluid handling structures, or various combinations thereof. Delivery device1350also includes pump1362, delivery reservoir1364, and outlet1366. Examples of fluid handling structures suitable for use in selected embodiments are described in U.S. Pat. Nos. 6,146,103 and 6,802,489, and in Krauβ et al., “Fluid pumped by magnetic stress”; Bearing a date of Jul. 1, 2004; pp. 1-3; located at: http://arxiv.org/PS_cache/physics/pdf/0405/0405025.pdf, all of which are incorporated herein by reference. Fluid handling structures may include, but are not limited to, channels, chambers, valves, mixers, splitters, accumulators, pulse-flow generators, and surge-suppressors, among others.

Previously described embodiments of delivery devices have include a delivery reservoir that is substantially chamber-like in shape. However, delivery fluid may be contained in fluid-containing structures having various shapes and configurations.FIG. 34illustrates a delivery device1400that includes a fluid-containing structure1402that takes the form of a channel. The fluid-containing structure1402may have at least one outlet1404through which a fluid may exit the fluid-containing structure1402to a downstream location; a delivery fluid1406contained within the fluid-containing structure1402; a primary material contained within the fluid-containing structure and having a controllable effective concentration in the delivery fluid; at least one electromagnetically responsive control element adapted1408for controlling the distribution of the primary material between a first active form1410carried in the delivery fluid and a second form1412in response to an incident electromagnetic control signal, the effective concentration being the concentration of the first active form in the delivery fluid; and a pump1414configured for pumping delivery fluid from the fluid-containing structure to the downstream location.

As noted previously, delivery devices as described herein may include various types of pumps. A pump suitable for use in a delivery device may include a mechanical pump, a displacement pump, a centrifugal pump, or a peristaltic pump. The choice of pump and method of construction thereof may depend upon the intended use of the delivery device, the delivery site, the dimensions of the delivery device, among other factors, as will be apparent to those of skill in the art. In some embodiments, the downstream location may be an environment. In some embodiments, the downstream location may be a downstream fluid handling structure, and in some embodiments, the downstream location may include a downstream environmental interface. An environmental interface may function to facilitate the distribution of a primary material into an environment.

FIG. 35depicts an example of a delivery device1450including an environmental interface1452. In the example ofFIG. 35, the environmental interface1452provides for the delivery of primary material1454into blood flowing through capillaries1456. Delivery device1450includes pump1458and a fluid-containing structure1460(here depicted as a delivery reservoir) containing delivery fluid1462carrying primary material1454. Environmental interface1452includes substrate material1464capable of supporting growth of capillaries1456. Distribution channel1466distributes delivery fluid1462to substrate material1464, where primary material1454may diffuse into capillaries1456and be picked up by the blood.

In other embodiments, a delivery device as depicted generally inFIG. 34may include any of various types of downstream fluid handling structures. The downstream fluid handling structure may include at least one channel, of the type depicted inFIG. 33, or at least one chamber, for example as depicted inFIG. 32or33. The downstream fluid handling structure may include at least one mixer (e.g.1360inFIG. 33or at least one splitter (e.g.1354inFIG. 33). In some embodiments, the downstream fluid handling structure may include a filter, for example, of the type depicted inFIG. 6D; it is contemplated that one or more filter may be placed at various downstream locations, not only at the outlet of the fluid-containing structure but potentially further downstream instead, or in addition.

FIG. 36depicts a method of delivery a fluid through the use of a delivery device as described herein. The basic method includes receiving an electromagnetic control signal from a remote controller at step1502; and responsive to the electromagnetic control signal, modifying an effective concentration of a primary material in a delivery fluid within a delivery reservoir at step1504.

As shown inFIG. 37, an expanded version of the method may include receiving an electromagnetic control signal from a remote controller at step1552; and responsive to the electromagnetic control signal, modifying an effective concentration of a primary material in a delivery fluid within a delivery reservoir at step1554; followed by an additional step of1556of ejecting the delivery fluid from the delivery reservoir.

FIG. 38provides further detail on a method including receiving an electromagnetic control signal from a remote controller at step1602; and responsive to the electromagnetic control signal, modifying an effective concentration of a primary material in a delivery fluid within a delivery reservoir at step1604(comparable to steps1502and1504as shown inFIG. 36). The method may include modifying the effective concentration of the primary material in the delivery fluid by modifying at least one characteristic of the delivery fluid, the effective concentration of the primary material in the delivery fluid dependent upon the at least one characteristic of the delivery fluid, as shown in alternative step1608inFIG. 38. In this and other figures boxes containing optional or alternative steps are surrounded by a dashed line. The at least one characteristic may include, for example, temperature, pH, polarity, osmolality or chemical activity. As another alternative, as indicated at alternative step1612inFIG. 38, the method may include modifying the effective concentration of the primary material in the delivery fluid by modifying at least one characteristic of the primary material, the solubility of the primary material in the delivery fluid being dependent upon the at least one characteristic of the primary material. The at least one characteristic includes temperature, charge, polarity, osmolality, conformation, orientation, or chemical activity. As a further alternative, indicated at1610inFIG. 38, the method may include modifying the effective concentration of the primary material in the delivery fluid by modifying at least one of a number of interaction sites in the delivery reservoir or an affinity of at least one interaction site in the delivery reservoir for the primary material. The affinity of the at least one interaction site for the primary material may be modified by modifying the temperature, charge, polarity, osmolality, surface energy, orientation, conformation, chemical activity or chemical composition of the at least one interaction site or in the vicinity of the at least one interaction site. The number of interaction sites may be modified by stretching, compressing, unfolding, or changing a conformation of at least a portion of the delivery reservoir, for example.

A method as shown inFIGS. 36-48may include receiving the electromagnetic control signal with an electromagnetically responsive material, which may include, for example, a permanently magnetizable material, a ferromagnetic material, a ferrimagnetic material, a ferrous material, a ferric material, a dielectric or ferroelectric or piezoelectric material, a diamagnetic material, a paramagnetic material, and an antiferromagnetic material. The method may include a step of ejecting the delivery fluid into an environment, which may include, for example, the body of an organism, a body of water, or a contained fluid volume. Alternative, the method may include ejecting the delivery fluid into a downstream environmental interface or a downstream fluid-handling structure, which may include a channel, a chamber, a mixer, a separator, or combinations thereof.

FIG. 39depicts a delivery system1650that includes a delivery device1652and a remote controller1654. Delivery device1652includes fluid-containing structure1656having at least one outlet1658through which fluid may exit the fluid-containing structure1656; a delivery fluid1660contained within the fluid-containing structure1656; a primary material1662contained within the fluid-containing structure1656and having a controllable effective concentration in the delivery fluid1660; and at least one electromagnetically responsive control element1664adapted for modifying the distribution of the primary material1662between a first active form carried in the delivery fluid and a second form in response to an incident electromagnetic control signal to modify the effective concentration of the primary material in the delivery fluid, the effective concentration being the concentration of the first active form in the delivery fluid. Remote controller1654includes an electromagnetic signal generator1668capable of producing an electromagnetic control signal sufficient to activate the electromagnetically responsive control element1664of the delivery device1652located in an environment1653to change the effective concentration of the primary material in the delivery fluid1660within the fluid-containing structure1656of the delivery device1652; and an electromagnetic signal transmitter1670capable of wirelessly transmitting the electromagnetic control signal1672to the electromagnetically responsive control element of the delivery device in the environment. The remote controller may include electrical circuitry1674, which may include at least one of hardware, firmware, or software configured to control generation of the electromagnetic control signal. The remote controller1654may include an electromagnetic signal generator1668configured to generate a static or quasi-static electrical field control signal, a static or quasi-static magnetic field control signal, a radio-frequency electromagnetic control signal sufficient, a microwave electromagnetic control, an infrared electromagnetic control signal, a millimeter wave electromagnetic control signal, an optical electromagnetic control signal, or an ultraviolet electromagnetic control signal sufficient to activate the electromagnetically responsive control element to control the effective concentration of the primary material within the fluid-containing structure. The remote controller may include an electromagnetic signal generator configured to generate a rotating electromagnetic control signal.

Delivery device1652may include a body structure1676adapted for positioning in an environment1653selected from a body of an organism, a body of water, or a contained fluid volume. For example, body structure1676may be adapted for positioning in a contained fluid volume selected from an industrial fluid volume, an agricultural fluid volume, a swimming pool, an aquarium, a drinking water supply, a potable water supply, and an HVAC system cooling water supply. Delivery device1652may include a pump1678, as described generally elsewhere herein.

The electromagnetically responsive control element1664may include a magnetically or electrically active material including at least one permanently magnetizable material, ferromagnetic material, ferrimagnetic material, ferrous material, ferric material, dielectric material, ferroelectric material, piezoelectric material, diamagnetic material, paramagnetic material, metallic material, or antiferromagnetic material. In some embodiments, the electromagnetically responsive control element may include a polymer, ceramic, dielectric, metal, shape memory material, or a combination of a polymer and a magnetically or electrically active component.

FIG. 40depicts a delivery system1700, including remote controller1702, and delivery device1704. Delivery device1704includes fluid-containing structure1656, having outlet1658and containing delivery fluid1660and primary material1662. Delivery device1704also includes electromagnetically responsive control element1664for controlling the effective concentration of primary material1662in delivery fluid1660. Delivery device1704may include body structure1676adapted for placement in environment1653, and pump1678. Delivery device1704may also include RFID1700. Remote controller1702includes RF interrogation signal generator1706for generating an RF interrogation signal1708, which may be tuned to the RFID. Remote controller1702includes electromagnetic signal generator1668, electromagnetic signal transmitter1670, electrical circuitry1674, which function generally as described in connection withFIG. 39.

FIG. 41illustrates a delivery system including a remote controller1850that produces electromagnetic control signal1852that is transmitted to delivery device1854in environment1856. Electromagnetic control signal1852is received by electromagnetically responsive control element1858in delivery device1854. Remote controller1850may include a signal input1851adapted for receiving a feedback signal1860sensed from an environment1856by a sensor1862, wherein the electromagnetic signal1852is produced based at least in part upon the feedback signal1860sensed from the environment. For example, the feedback signal1852may correspond to the osmolality or the pH of the environment, the concentration or chemical activity of a chemical in the environment, a temperature or pressure of the environment, or some other sensed signal. Remote controller1850may include electrical circuitry1864, signal generator1866, signal transmitter1868, and memory1870. Feedback from sensor1862may be sent over a wire connection or, in some embodiments, transmitted wirelessly. Remote controller may include a signal input adapted for receiving a feedback signal corresponding to one or more parameters sensed from the environment, wherein the electromagnetic control signal is produced based at least in part upon the feedback signal sensed from the environment. For example, the feedback signal corresponds to the concentration or chemical activity of a chemical in the environment.

FIG. 42illustrates another embodiment of a delivery system, including remote controller1900, which transmits electromagnetic control signal1902to delivery device1904in environment1906. Remote controller1900may include a signal input1908adapted for receiving a feedback signal1912from sensor1910in delivery device1904. Electromagnetic control signal1902may be produced based at least in part upon the feedback signal1912corresponding to one or more parameters sensed from the delivery device. In some embodiments, the feedback signal may correspond to the concentration or chemical activity of a chemical within or around the delivery device. In some embodiments, the feedback signal from the delivery device may correspond to the osmolality or the pH within or around the delivery device, the concentration or chemical activity of a chemical within or around the delivery device, a temperature or pressure within or around the delivery device, the pumping rate of the delivery device, or some other parameter sensed from the delivery device. In others, the feedback signal may correspond to the pumping rate of the delivery device, produced, for example, by pump1922. In some embodiments, sensor1910may be configured for detecting at least one parameter from at least a portion of an environment surrounding the delivery device. The electromagnetic signal1902may be determined based at least in part upon the feedback signal1912. Examples of sensors are described in U.S. Pat. No. 6,935,165, and U.S. Patent Publication 2004/0007051, both of which are incorporated herein by reference. Delivery device1904includes electromagnetically responsive control element1920. Feedback signal1912may be transmitted wirelessly back to remote controller1900. Remote controller1900may include processor1914, signal generator1916, signal transmitter1918, and memory1924.

As illustrated inFIG. 43, in some embodiments, the remote controller may be configured to receive user input of control parameters. Remote controller1950includes input1960for receiving input of information or instructions from a user such as, for example, commands, variables, durations, amplitudes, frequencies, waveforms, data storage or retrieval instructions, patient data, etc. As in the other embodiments, remote controller1950transmits electromagnetic control signal1952to delivery device1954in environment1956, where it activates electromagnetically responsive control element1958. Input1960may include one or more input devices such as a keyboard, keypad, microphone, mouse, etc. for direct input of information from a user, or input1960may be any of various types of analog or digital data inputs or ports, including data read devices such as disk drives, memory device readers, and so forth in order to receive information or data in digital or electronic form. Data or instructions entered via input1960may be used by electrical circuitry1962to modify the operation of remote controller1950to modulate generation of an electromagnetic control signal1952by signal generator1964and transmission of the control signal1952by transmitter1966.

FIG. 44illustrates a delivery system that includes a plurality of delivery devices, where two or more of the plurality of delivery devices are controlled by the remote controller. A delivery device may include a plurality of selectively activatable control elements, each associated with a particular fluid handling element, which may thus be controlled to perform multiple fluid-handling or reaction steps in a particular sequence. It is also contemplated that a delivery system may include a plurality of delivery devices which may be of the same or different types. As shown inFIG. 44, a delivery system2000may include a plurality of identical delivery devices2002distributed throughout an environment2004in order to perform a particular chemical reaction or process at a plurality of locations within the environment, and controlled by a remote controller2006. Alternatively, a delivery system may include a plurality of different delivery devices at different locations within an environment, each performing or controlling a reaction suited for the particular location. The invention as described herein is not limited to devices or systems including any specific number or configuration of electromagnetically responsive control elements within a delivery device, or specific number or configuration of delivery devices or remote controllers within a delivery system. Depending upon the particular application of a system, electromagnetically responsive control elements and/or delivery devices may be controlled in a particular pattern to producing a desired distribution of a delivery material in an environment. Control of such systems may be performed with the use of suitable hardware, firmware, or software, through one or a plurality of remote controllers.

The remote controller used in the system depicted inFIG. 44may include an electromagnetic signal generator capable of producing an electromagnetic control signal sufficient to activate electromagnetically responsive control elements in a plurality of delivery devices located in an environment to change an effective concentration of primary material in a delivery fluid within a fluid-containing structure of each of the devices. In a related embodiment, the remote controller may include a plurality of signal inputs adapted for receiving signals from the plurality of delivery devices, the plurality of signal inputs coupled to a microprocessor configured to generate the electromagnetic control signal based upon the plurality of signals.

Selective activation or control of electromagnetically responsive control elements may be achieved by configuring electromagnetically responsive control elements to be activated by electromagnetic control signals having particular signal characteristics, which may include, for example, particular frequency, phase, amplitude, temporal profile, polarization, and/or directional characteristics, and spatial variations thereof. For example, different control elements may be responsive to different frequency components of a control signal, thereby allowing selective activation of the different control elements. The remote controller may be configured to produce a rotating electromagnetic signal, the rotating electromagnetic signal capable of activating the two or more delivery devices independently as a function of the orientation of the rotating electromagnetic signal.

As shown inFIG. 45, in still other embodiments, a delivery system2050may include a delivery device2052that includes a plurality of electromagnetically responsive control elements2054, responsive to one or more remote controller2056. A plurality of control elements2054may be used, for example, to control a plurality of locations or functions in delivery device2052.

As shown inFIG. 46, in some embodiments, a delivery system2101or may include a plurality of delivery devices2102,2104,2106, and2108, and a plurality of remote controllers2100a,2100b,2100c. As shown inFIG. 46, each delivery device may be controlled by one or more control signals produced in a distributed fashion by two or more of the plurality of remote controllers2100a-2100c.

As shown inFIG. 47, in some embodiments a delivery system2151may include a plurality of delivery devices2152a,2152b, and2152cand a plurality of remote controllers2150a,2150b, and2150c, each delivery device may be controlled by a separate remote controller, for example delivery device2152acontrolled by remote controller2150a, delivery device2152bcontrolled by remote controller2150b, and delivery device2152ccontrolled by remote controller2150c.

In still other embodiments, as shown inFIG. 48, a remote controller2200may include a plurality of transmission channels2204a,2204b,2204c, and2204d, for example (more or fewer channels may be used, without limitation). Remote controller2200may also include channel allocation hardware or software2206configured to allocate usage of the plurality of transmission channels2204a-2204dfor the transmission of the electromagnetic control signal from signal transmitter2208to selected delivery devices of the plurality of delivery devices2202a-2202f.

In another embodiment of a delivery system2250shown inFIG. 49, the remote controller2252may include encryption hardware or software2262configured to encrypt one or more control signal components, wherein the encrypted one or more control signal components are receivable by a delivery device2254including a corresponding decryption key2264. Remote controller2252may include signal generator2256, signal transmitter2258, and electrical circuitry2260, as described generally elsewhere.

In another embodiment of a delivery system2300shown inFIG. 50, the remote controller2302may include authentication hardware or software2312configured to perform an authentication procedure with a delivery device2304, wherein the remote controller2302is configured to produce activation of the electromagnetically responsive control element2316of an authenticated delivery device but not the electromagnetically responsive control element of a non-authenticated delivery device. Again, remote controller2302may include signal generator2306, signal transmitter2308, and electrical circuitry2310, as described generally elsewhere, and authentication portion2314, which may include hardware, firmware or software configured for performing an authentication protocol with remote controller2302.

Referring back toFIG. 40, remote controller1702may include an interrogation signal generator1706for generating a transmittable RFID interrogation signal. The remote controller may also include an interrogation signal transmitter for transmitting the transmittable RFID interrogation signal; an interrogation signal receiver for receiving a returned RFID interrogation signal from an RFID in a delivery device; and RFID detection circuitry configured to detect the presence of a selected RFID from a returned RFID interrogation signal. Upon detection of the presence of the selected RFID, to remote controller1702may generate and transmit a control signal configured for receipt by the delivery device including the selected RFID.

In various embodiments of the remote controller described herein, the generated electromagnetic control signal may have a defined magnetic field strength, or alternatively, or in addition, a defined electric field strength. Depending upon the intended application, the electromagnetic control signal may have signal characteristics sufficient to produce a change in dimension of the electromagnetically responsive control element, a change in temperature of at least a portion of the electromagnetically responsive control element, a change in conformation or configuration of the electromagnetically responsive control element, or a change in orientation or position of the electromagnetically responsive control element. The remote controller may include an electromagnetic signal generator that includes an electromagnet or electrically-polarizable element, or at least one permanent magnet or electret.

FIG. 51depicts the steps of a method of delivering a material, comprising delivering an electromagnetic distribution control signal to an environment containing a delivery device, the delivery device including an electromagnetically responsive control element and a fluid-containing structure containing a delivery fluid and a quantity of a primary material distributed between a first active form carried in the delivery fluid and a second form according to a first distribution, the primary material distributed according to the first distribution having a first effective concentration in the delivery fluid equal to the concentration of the first active form in the delivery fluid, the electromagnetic distribution control signal having signal characteristics receivable by the electromagnetically responsive control element and sufficient to produce a change in the distribution of the primary material between the first active form and the second form to a second distribution, the primary material distributed according to the second distribution having a second active concentration in the delivery fluid, at step2352; and delivering an electromagnetic delivery control signal to the environment containing the delivery device, the electromagnetic delivery control signal sufficient to produce pumping of the delivery fluid out of the fluid-containing structure, the delivery fluid containing the primary material at the second effective concentration in the delivery fluid at step2354.

FIG. 52shows further variations of the method ofFIG. 51. The method ofFIG. 52include steps of delivering and electromagnetic distribution control signal at step2402and delivering an electromagnetic delivery control signal at step2404(e.g., as in FIG.51), followed by a step of generating an electromagnetic control signal according to a number of optional steps. For example, the method may include generating and transmitting the electromagnetic control signal to the delivery device with a remote controller, as shown at2406a. Alternatively, the method may include generating a first electromagnetic control signal sufficient to produce a change in effective concentration of a primary material in a delivery fluid in a delivery reservoir of a delivery device; and generating a second electromagnetic control signal sufficient to cause delivery fluid containing primary material in solution to be released from the delivery reservoir into the environment, as shown at2406b. Or, the method may include generating a first electromagnetic control signal having frequency and magnitude sufficient to produce heating of a heating element in or near the delivery reservoir, as shown at2406c. Alternatively, the method may include generating a first electromagnetic control signal having frequency and magnitude sufficient to produce cooling of a cooling element in or near the delivery reservoir, as shown at2406d, generating a first electromagnetic field having frequency and magnitude sufficient to produce a conformation change of a molecular structure, as shown at2406e, or generating a first electromagnetic field having frequency and magnitude sufficient to produce a volume change of a material a molecular structure, as shown at2406f.

FIG. 53shows a method of delivering a material including pumping a delivery fluid containing a primary material from a delivery reservoir of a delivery device to a downstream location at a first pumping rate at step2452; and controlling the effective concentration of the primary material in the delivery fluid in response to a remotely transmitted electromagnetic control signal at step2454. In some embodiments, the first pumping rate may be a constant pumping rate. In some embodiment, the method may include varying the rate of delivery of the primary material to the downstream location by varying the effective concentration of the primary material in the delivery fluid in response to the remotely transmitted electromagnetic control signal. In other embodiments, the first pumping rate may be a time-varying pumping rate. In such embodiments, the method may include controlling the rate of delivery of the primary material to the downstream location by controlling both the effective concentration of the primary material in the delivery fluid and the pumping rate. The first pumping rate is modifiable in response to a remotely transmitted electromagnetic control signal, for example. The method may include controlling the effective concentration of the primary material in the delivery fluid through activation of an electromagnetically responsive control element in the delivery device by the remotely transmitted electromagnetic control signal, for example by heating of the electromagnetically responsive control element, cooling of the electromagnetically responsive control element. In some variants of the method, activation of the electromagnetically responsive control element may include a change in at least one dimension of the electromagnetically responsive control element, a change in orientation of the electromagnetically responsive control element, or a change in conformation of the electromagnetically responsive control element.

FIG. 54shows a method of delivering a material, including receiving a first electromagnetic control signal with a first electromagnetically responsive control element in a delivery device, the delivery device including a fluid-containing structure containing a delivery fluid and a primary material distributed between a first active form carried in the delivery fluid and a second form, the primary material having a first effective concentration in the delivery fluid equal to the concentration of the first active form in the delivery fluid at step2502; responsive to receipt of the first electromagnetic control signal by the first electromagnetically responsive control element, modifying the distribution of the primary material between the first active form and the second form, the primary material having a second effective concentration in the delivery fluid following the modification of the distribution of the primary material between the first active form and the second form at step2504; and pumping the delivery fluid containing the primary material at the second effective concentration from the fluid-containing structure of the delivery device to a downstream location at step2506. In the method ofFIG. 54, the primary material has a different stability in the first active form than in the second form, a different immunogenicity in the first active form than in the second form, a different reactivity in the first active form than in the second form, or a different activity in the first active form than in the second form.

In a variant of the method ofFIG. 54, shown inFIG. 55(with steps2552-2556the same as steps2502-2506), the method may include the additional step of filtering the second form of the primary material from the delivery fluid prior to pumping the delivery fluid containing the primary material at the second effective concentration from the fluid-containing structure of the delivery device to a downstream location2558.

In the method ofFIG. 54, in some embodiments the first effective concentration may be lower than the second effective concentration, and some embodiments first effective concentration may be higher than the second effective concentration. The method may include modifying the rate of pumping of the delivery fluid to the downstream location responsive to receipt of a second electromagnetic control signal by a second electromagnetically responsive control element. In some embodiments, the first electromagnetic control signal and the second electromagnetic control signal may be the same electromagnetic control signal. In other embodiments, the first electromagnetic control signal may be different than the second electromagnetic control signal. In some embodiments, the first electromagnetically responsive control element and the second electromagnetically responsive control element may be the same electromagnetically responsive control element, while in other embodiments, the first electromagnetically responsive control element may be a different control element than the second electromagnetically responsive control element. “Different” control elements may be control elements of different types, or distinct control elements that are of the same type.

FIG. 56depicts further variants on the method ofFIG. 54. Steps2602through2606are the same as steps2502-2506inFIG. 54. Steps2608a-2608falternative steps for modifying the distribution of primary material between the first active form and the second form. Step2608aincludes modifying the distribution of primary material in response to receipt of the first electromagnetic control signal by modifying a pressure within the fluid containing structure, step2608bincludes modifying the distribution of primary material in response to receipt of the first electromagnetic control signal by modifying a temperature within the fluid containing structure, step2608cincludes modifying the distribution of primary material in response to receipt of the first electromagnetic control signal by modifying a volume of the fluid containing structure, step2608dincludes modifying the distribution of primary material in response to receipt of the first electromagnetic control signal by producing vibration within the fluid containing structure, step2608eincludes modifying the distribution of primary material in response to receipt of the first electromagnetic control signal by producing fluid mixing within the fluid containing structure, and step2608fincludes modifying the distribution of primary material in response to receipt of the first electromagnetic control signal by modifying a number of available interaction sites within the fluid containing structure, the available interaction sites capable of interacting with the primary material to produce the second form of the primary material.

FIG. 57illustrates a method of delivering a material, including, at step2652, introducing a delivery device into an environment, the delivery device including an electromagnetically responsive control element, a pump, a fluid-containing structure containing a delivery fluid and a quantity of a primary material, the primary material being distributed between a first active form carried in the delivery fluid and a second form according to a first distribution in which the primary material has a first effective concentration in the delivery fluid equal to the concentration of the first active form in the delivery fluid, and wherein the electromagnetically responsive control element is configured to modify the distribution of primary material between the first active form and the second form, and a pump, the pump being activatable for pumping delivery fluid from the fluid-containing structure to a downstream location. At step2654, the method includes a step of delivering an electromagnetic distribution control signal to the environment with signal characteristics selectively receivable by the electromagnetically responsive control element and sufficient to produce a change in the distribution of the primary material between the first active form and the second from to a second distribution, the primary material distributed according to the second distribution having a second effective concentration in the delivery fluid. The pump may be activated to pump delivery fluid containing the primary material at the second effective concentration out of the fluid containing structure. In one variant, the pump may be activated prior to introducing the delivery device into the environment. In another variant, the pump may be activated upon introduction of the delivery device into the environment. In still another variant, the pump may be activated subsequent to introducing the delivery device into the environment. The method as depicted inFIG. 57may also include delivering an electromagnetic delivery control signal having signal characteristics selectively receivable by a second electromagnetically responsive control element in the delivery device to produce the pumping of the delivery fluid containing the primary material at the second effective concentration out of the fluid-containing structure. The primary material may have a different immunogenicity, reactivity, or stability when it is in the first active form than when it is in the second form.

FIG. 58illustrates a method of controlling a delivery device, which includes the steps of generating an electromagnetic control signal including frequency components absorbable by an electromagnetically responsive control element of a delivery device in an environment, the delivery device including a fluid-containing structure containing a delivery fluid and a quantity of primary material, the primary material being distributed between a first active form and a second form and having an effective concentration in the delivery fluid equal to the concentration of the first active form in the delivery fluid, wherein the effective concentration of the primary material in the delivery fluid is controllable by the electromagnetically responsive control element at2702; and remotely transmitting the electromagnetic control signal to the delivery device with signal characteristics sufficient to activate the electromagnetically responsive control element in the delivery device to control the effective concentration of primary material in the delivery fluid in the delivery device at2704.

FIG. 59illustrates an expansion of the method shown inFIG. 58, with steps2752and2754being the same as steps2702and2704, respectively, inFIG. 58, with a number of alternative steps relating to generation of the electromagnetic control signal. Step2756aincludes generating the electromagnetic control signal and transmitting the electromagnetic control signal to the delivery device with a remote controller. Step2756bincludes generating the electromagnetic control signal and transmitting the electromagnetic control signal to the delivery device with two or more remote controllers. Step2756cincludes generating the electromagnetic control signal from a model-based calculation. Step2756dincludes generating the electromagnetic control signal based on a stored pattern. As yet another alternative, step2756eincludes generating the electromagnetic control signal based upon a feedback control scheme. A feedback control scheme may be, for example, a variable feedback control scheme.

A further expansion the method shown inFIG. 58may include the additional steps depicted inFIG. 60, namely receiving a feedback signal corresponding to one or more parameters sensed from the environment at2802; and based upon the feedback signal, generating the electromagnetic control signal with signal characteristics expected to produce a desired feedback signal, at2804. In some embodiments, receiving the feedback signal from the environment may include receiving signals from at least one sensor in the environment, while in other embodiments it may include receiving the feedback signal from the environment includes receiving signals from two or more sensors in the environment. Receiving the feedback signal from the environment may include receiving a measure of the concentration or chemical activity of a chemical within at least a portion of the environment.

In another variation of the method shown inFIG. 58, shown inFIG. 61, the method may include the additional steps of receiving a feedback signal from the delivery device at2852; and based upon the feedback signal, generating an electromagnetic control signal having signal characteristics that are expected to produce a desired feedback signal at2854. Receiving a feedback signal from the delivery device may include receiving signals from at least one sensor in the delivery device, or alternatively, receiving a feedback signal from the delivery device may include receiving signals from two or more sensors in the delivery device. For example, receiving the feedback signal from the delivery device may include receiving a signal representing a concentration or chemical activity of a chemical within or around the delivery device.

Another variation of the method depicted inFIG. 58, shown inFIG. 62, may include the additional steps of receiving user input of one or more control parameters at2892; and based upon the one or more control parameters, generating an electromagnetic control signal having signal characteristics expected to produce a desired effective concentration of primary material in the delivery fluid, as2894. The desired effective concentration of primary material in the delivery fluid may be an effective concentration sufficient to produce a desired rate of delivery of the first active form of the primary material to the environment by the delivery device.

Further additions to the method depicted inFIG. 58include steps of activating the electromagnetically responsive control element to produce heating or cooling, or activating the electromagnetically responsive control element to produce a change in configuration of the electromagnetically responsive control element. Steps of generating an electromagnetic control signal and remotely transmitting the electromagnetic control signal to the delivery device, as shown inFIG. 58, may be performed according to instructions provided in the form of software, hardware or firmware. In some method embodiments, the steps of generating an electromagnetic control signal and remotely transmitting the electromagnetic control signal to the delivery device may be performed according to instructions distributed among a plurality of controllers or transmitters.

Generating the electromagnetic control signal includes generating a static or quasi-static magnetic field, static or quasi-static electrical field, radio-frequency electromagnetic signal, microwave electromagnetic signal, millimeter wave electromagnetic signal, optical electromagnetic signal, which may be an optical electromagnetic signal is an infrared electromagnetic signal, or generating an ultraviolet electromagnetic signal. Generating the electromagnetic control signal may be performed under software control.

FIG. 63depicts a further variation of the method shown inFIG. 58, with steps2902and2904corresponding to steps2702and2704, respectively. The method includes the additional step of modifying the concentration of the primary material within the delivery fluid in the fluid-containing structure of the delivery device by modifying the area of an interaction region within the fluid containing structure of the delivery device at2906. Modifying the area of the interaction region includes increasing the area of the interaction region, as at2906a, or alternatively, decreasing the area of the interaction region, as2906b. In the case that the area is increased, and the interaction region includes interaction sites, and increasing the area of the interaction region may include increasing the distances between interaction sites in the interaction region, as at2908a, or increasing the area of the interaction region includes increasing a number of interaction sites in the reaction area, as at2908b. In the case that the area is decreased, as at2906b, and the interaction region includes interaction sites, decreasing the area of the interaction region may include decreasing distances between one or more interaction sites in the interaction region, as at2910a, or decreasing a number of interaction sites in the reaction area as at2910b.

FIG. 64depicts a further variation of the method shown inFIG. 58, with steps2952and2954corresponding to steps2702and2704, respectively. The method further includes a further step of modifying the concentration of the primary material in the delivery fluid by modifying a condition at an interaction region within the fluid-containing structure, at2956. Modifying a condition at the interaction region may include heating or cooling at least a portion of the interaction region, as shown at2958a, modifying the osmolality or the pH of at least a portion of the interaction region, at2958b, modifying the surface charge of at least a portion of the interaction region, at2958c, or modifying the surface energy of at least a portion of the interaction region, as1958d.

In another variation, shown inFIG. 65, the method includes a further step of modifying a condition at the interaction region by modifying a condition within the fluid-containing structure, as indicated at step3006(steps3002and3004correspond to steps2702and2704inFIG. 58). Modifying a condition within the fluid-containing structure may include modifying the volume of the fluid-containing structure, as shown at3008a, heating or cooling at least a portion of the fluid-containing structure, as shown at3008b, or modifying the osmolality or the pH within at least a portion of the fluid-containing structure, as shown at3008c.

Software may be used in performing various of the methods as described herein. Such software includes software for controlling delivery of a material from a delivery device, including instructions for generating an electromagnetic control signal including frequency components absorbable by an electromagnetically responsive control element of a delivery device in an environment, the delivery device including a fluid-containing structure containing a delivery fluid and a quantity of primary material, the primary material being distributed between a first active form and a second form and having an effective concentration in the delivery fluid equal to the concentration of the first active form in the delivery fluid, wherein the effective concentration of the primary material in the delivery fluid is controllable by the electromagnetically responsive control element; and instructions for controlling the transmission of the electromagnetic control signal to the delivery device with signal characteristics sufficient to activate the electromagnetically responsive control element in the delivery device to control the effective concentration of primary material in the delivery fluid in the delivery device.

The software may include instructions for generating the electromagnetic control signal include instructions for calculating the electromagnetic control signal based on a model. The instructions for generating the electromagnetic control signal may include instructions for generating the electromagnetic control signal based on a pattern stored in a data storage location, or instructions for generating the electromagnetic control signal based upon a feedback control algorithm. For example, the instructions for generating the electromagnetic control signal may include instructions for generating the electromagnetic control signal based upon a variable feedback control algorithm. The software may include instructions for receiving a feedback signal corresponding to one or more parameters sensed from the environment; and instructions for generating the electromagnetic control signal based at least in part upon the received feedback signal, the electromagnetic control signal having signal characteristics expected to produce a desired feedback signal. Some embodiments of the software may include instructions for receiving a feedback signal from the delivery device; and instructions for generating the electromagnetic control signal based at least in part on the received feedback signal, the electromagnetic control signal having frequency composition and amplitude expected to produce a desired feedback signal. In some embodiments, the software may include instructions for receiving user input of one or more control parameters; and instructions for generating the electromagnetic control signal based at least in part upon the one or more control parameters. In some embodiments, the software may include instructions for performing encryption of the electromagnetic control signal. Instruction may be included for performing an authentication procedure between a remote controller transmitting the electromagnetic control signal and a delivery device including the electromagnetically responsive control element intended to be activated by the electromagnetic control signal. At least a portion of the instructions generating the electromagnetic control signal and the instruction for controlling the transmission of the electromagnetic control signal are executable in distributed fashion on a plurality of microprocessors. Some embodiments of the software may include channel allocation instructions configured to control the allocation of control signal transmission channels for transmission of a plurality of control signals to a corresponding plurality of delivery devices.

Those skilled in the art will recognize that it is common within the art to describe devices for detection or sensing, signal processing, and device control in the fashion set forth herein, and thereafter use standard engineering practices to integrate such described devices and/or processes into fluid handling and/or delivery systems as exemplified herein. That is, at least a portion of the devices and/or processes described herein can be integrated into a fluid handling and/or delivery system via a reasonable amount of experimentation.

Those having skill in the art will recognize that systems as described herein may include one or more of a memory such as volatile and non-volatile memory, processors such as microprocessors and digital signal processors, computational-supporting or -associated entities such as operating systems, user interfaces, drivers, sensors, actuators, applications programs, one or more interaction devices, such as data ports, control systems including feedback loops and control implementing actuators (e.g., devices for sensing osmolality, pH, pressure, temperature, or chemical concentration, signal generators for generating electromagnetic control signals). A system may be implemented utilizing any suitable available components, combined with standard engineering practices.

Although the methods, devices, systems and approaches herein have been described with reference to certain preferred embodiments, other embodiments are possible. As illustrated by the foregoing examples, various choices of remote controller, system configuration and fluid handling/delivery device may be within the scope of the invention. As has been discussed, the choice of system configuration may depend on the intended application of the system, the environment in which the system is used, cost, personal preference or other factors. System design, manufacture, and control processes may be modified to take into account choices of use environment and intended application, and such modifications, as known to those of skill in the arts of device design and construction, may fall within the scope of the invention. Therefore, the full spirit or scope of the invention is defined by the appended claims and is not to be limited to the specific embodiments described herein.

While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. It is intended that the various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.