Patent ID: 12220556

DETAILED DESCRIPTION

Aspects of the invention are disclosed in the following description and related drawings directed to specific embodiments of the invention. Those skilled in the art will recognize that alternate embodiments may be devised without departing from the spirit or the scope of the claims. Additionally, well-known elements of exemplary embodiments of the invention will not be described in detail or will be omitted so as not to obscure the relevant details of the invention. Further, to facilitate an understanding of the description discussion of several terms used herein follows.

As used herein, the word “exemplary” means “serving as an example, instance or illustration.” The embodiments described herein are not limiting, but rather are exemplary only. It should be understood that the described embodiments are not necessarily to be construed as preferred or advantageous over other embodiments. Moreover, the terms “embodiments of the invention”, “embodiments” or “invention” do not require that all embodiments of the invention include the discussed feature, advantage or mode of operation.

As used herein, electroosmotic element (EOE) means a structure that has a working fluid move through when a voltage is applied across the structure. Because the fluid moves towards the negative terminal, by alternating the polarity of the applied voltage the electroosmotic element can create reciprocating fluid motion.

As used herein, a bidirectional electroosmotic pump (EOP) means a structure that uses an EOE with an alternating polarity to drive a payload fluid, at a precise and low flowrate, in two directions.

FIG.1Adepicts an embodiment of an electroosmotic pump device100with an external housing102surrounding an inner assembly104. It may be appreciated that the internal elements may be formed out of any of a variety of materials or combinations thereof, based on implementation and use. Further, in the embodiments, the components utilized in the pump assembly may be biocompatible with the human body and may be absent of any ferrous-containing elements, which can mitigate adverse effects related to MRI equipment or imaging conditions and allow the device to be both MRI-compatible and devoid of any radiological artifact. Thus, in some further embodiments, the embodiments may include a pump, or pumps, that are MRI-safe (i.e. the device, when used in the MRI environment, presents no additional risk to the patient or other individual, but it may affect the quality of the diagnostic information), MRI-compatible (i.e. a device that is MRI safe when used in the MRI environment, to neither significantly affect the quality of the diagnostic information nor have its operations affected by the MRI system), and/or MRI-lucent (i.e., a device that is MRI compatible and when used in the MRI environment, is radiographically invisible on MR imaging and thereby able to prevent unwanted artifact and prevent the risk of suboptimal MR imaging value for pathology assessment). The external housing102may be cylindrical or, in other embodiments, adjusted to a different shape which is lower profile for human body implantation to avoid any visible deformity when placed under skin and soft tissue. The external housing102of the device may be formed from a biocompatible and durable plastic or photocured resin or any other safe and sterilizable material that is FDA-approved for reconstructive purposes. For example, the external housing102may be formed from any alloplastic material or paramagnetic material (i.e. titanium) capable of human use and compatible with the working fluid and payload fluid. Other shapes and/or materials may be used based on the use and implementation of the pump for certain disease conditions and anatomical variance (i.e. placement within head, chest, abdomen, joint space, and/or extremity, as desired). Each end of the external housing102may include one or more valves118to facilitate the flow of a payload fluid120without backflow. The one or more valves118may be, for example, duckbill valves, and may be formed from silicone, Viton, fluorosilicone, or another MRI-lucent material. In an exemplary embodiment, the valves118may be duckbill valves, which may support an effective low flow rate system because of the small amount of pressure required to open them and the lack of resistance created by the valves118. Other types of valve systems may include, but are not limited to, diaphragm valves, custom valve flaps, umbrella valves, or other flow metering systems, as desired. In an exemplary embodiment, there may be a set of four valves, two of which facilitate the flow of fluid into the pump and two of which facilitate driving fluid out of the pump. In other embodiments, there may be fewer valves utilized, which may be accomplished, for example, by combining fluid channels so there is one inlet and one outlet valve. It may be understood that in other embodiments, only two valves may be used, or more or less than four valves may be used, depending on application. In an embodiment, a bi-directional pump may be desired over a uni-directional pump, because the bi-directionality may enable the delivery of a payload fluid, such as, for example, a medicine to be directly delivered to the brain or targeted body part, that is different than the working fluid within the EOP. Further, the added duplicity of two catheters per pump (versus one catheter per pump) may mitigate instances of unexpected catheter blockage secondary to normal physiologic scar tissue following placement, which may be a safer and more effective option for chronic medicine delivery.

FIG.1Bdepicts an embodiment of the cross-sectional view of the device inner assembly104with parts of the inner assembly shown. In an embodiment, the inner assembly104may contain the electroosmotic element106which may be contained by a holder112and may receive a voltage from electrodes108. The holder112can be connected to bellows110which can contain a working fluid114. External to, or surrounding, the inner assembly104there may be the payload fluid120which may be contained by the external housing102. It should be understood that this is merely an exemplary configuration and, depending on application or location of an implant, different configurations may be used. In addition, the bellows can be shaped and designed with various forms to improve long-term conditions, enhance function, and/or minimize wear, tear, or degradation.

FIG.1Cdepicts a cross section of an embodiment of the electroosmotic pump device100, with internal elements of the bidirectional pump shown. It may be appreciated that the internal elements may be formed out of any of a variety of materials or combinations thereof, based on implementation and use. In an embodiment, the electroosmotic device100may include an electroosmotic element106that may be formed by, for example, using a ceramic cylinder, or another porous material, and which may be contained by a holder112, which may be formed, for example, with high-density polyethylene (HDPE), polyphenylene sulfide, polycarbonate, photocuring resin, or another material or set of materials that can bond around the external surface of the electroosmotic element. In an exemplary embodiment, a ceramic element may be incorporated to avoid any ferrous materials and to assure MRI compatibility and/or MRI lucency. This may allow the pump(s) and/or any implanted devices using the pump(s) to increase long-term patient safety and enhance pump functionality, for example with respect to MR imaging conditions, especially in instances where the patient's disease, like chronic brain or spine diseases, requires serial MR imaging. The electroosmotic element106may be porous, which may enable the working fluid to flow through, causing the electroosmotic effect that drives the bidirectional electroosmotic pump.

Still referring toFIG.1C, on either side of the electroosmotic pump100may be electrodes108, which may be formed of platinum or another conductive material in order to produce a voltage differential to move the working fluid through the electroosmotic element. Platinum, in an embodiment, may be utilized for favorable material properties with respect to, for example, ductility and chemical inertness. In an embodiment, platinum may be utilized because it can interact with various working fluids while remaining inert. Further, the platinum may be formed into a desirable shape while maintaining electrical contact with the electroosmotic element106. Other, non-platinum, materials may develop an oxidation layer when an electrical charge is applied thereby reducing the conductivity of the material and resulting bidirectional electroosmotic pump performance. The electrodes108may deliver a voltage to the electroosmotic element106that can cause pumping actuation to occur. The electroosmotic element holder112may be connected to each bellows110, which may be positioned on either side of the holder112, and which may be capped by plugs122. The bellows110may be formed from titanium, silicone, fluoroelastomers, or other elastic materials such as latex that are compatible with the working fluid and the plugs122may be formed from resin, as desired. The bellows110shape in the embodiments may be such that it may minimize size, maximize function, and/or reduce long-term degradation associated with frequent or repetitive movements or from long-term contact with the working fluid and payload fluid as may be required in use in some embodiments. The plug can be made from resin printing, silicone, plastics, or another material which may reliably bind to the bellows110. The plugs122can also be drilled so as to allow for filling with the working fluid114, and then may be resealed with additional resin and UV curing. The bellows110may contain a working fluid114which may facilitate the deformation of the bellows110. This working fluid114, in an exemplary embodiment, may be strategically chosen based on its safety profile, polarity, it being a dielectric (which means a polarizable insulator), compatibility with the surrounding materials, such as the bellows, EOE, and holder, and/or its stability over time with respect to bubble formation, and may be, but is not limited to, ethanol, DI water, or dimethyl sulfoxide (DMSO). In other embodiments the working fluid114may be another polar fluid compatible with the pump materials, and some embodiments may require the working fluid114to be particle free, as particles in the working fluid114may clog the pores in the EOE, which may prevent the movement of the working fluid114, which may reduce flow rate or cease pumping entirely. In some embodiments the fluid may have a viscosity similar to water, and the fluid may be sterilized with a method compatible with the bidirectional pump. For example, with ethylene oxide sterilization. Surrounding the holder112and the bellows110may be a casing116(for example formed of resin) that can contain an inner assembly104and the payload fluid120. On each end of the casing116there may be two valves118, for example formed of silicone, which can facilitate flow of the payload fluid120in and out of the electroosmotic pump100.

FIG.2Adepicts an exemplary embodiment of the inner assembly204. It may be appreciated that the parts may be formed out of any of a variety of biocompatible materials or combinations thereof for human body implantation, based on implementation and desired use, and/or for implantation in various animals. In this embodiment, the bellows210may extend from either end of the holder212and can be capped222to prevent the working fluid214from escaping. In this embodiment, the elastic design of the bellows210may facilitate their expansion and contraction in a precise manner so as to prevent over or under delivery of medicine, which could result in impaired patient safety, adverse drug events, and/or patient death. For example, the bidirectional pump may facilitate a flow rate of 0.5-5 μl/min, which may be desirable for specific applications including convection-enhanced delivery (CED). It may be appreciated that another configuration of the bellows210and their plugs may be used, depending on the implementation or packaging of the implant. Furthermore, in an embodiment, a sensor located inside of the implant may be utilized to provide, for example, an embedded biosensing system and/or data as to when the bellows210are in use or operation, maximally/partially flex and maximally/partially unflex, and also to alert a patient and/or healthcare provider of improper pump function with enhanced safety alarms. In other embodiments, custom rubber domes may replace the bellows210and plugs. In such an embodiment, the state of the pumping cycle can be detected using, for example, IR LEDs and phototransistors to determine the extent of deformation or expansion. Based on the reading, the pump can alternate flow direction. Another alternative embodiment may include custom conductive rubber domes which can be formed into various shapes. The conductive diaphragms may come into contact with the electrodes208and send signals to alternate the polarity. Further alternate embodiments could include latex coated in graphene, or a fluid barrier where a fluid membrane is used instead of a physical piece. This fluid membrane could be, for example, air in a microfluidic channel, a liquid metal, oil, or other fluid that may not mix with either the working or payload fluid.

FIG.2Bdepicts an embodiment of a cross-sectional view of the inner assembly204. The electroosmotic element206may be supported by the holder212, and electrodes208may be on either side of the electroosmotic element206and extend out of the inner assembly204. The electrodes208may extend to receive a voltage and deliver it to the electroosmotic element206. In this embodiment, the working fluid214may be enclosed within the bellows210to drive their movement. In some further embodiments, a sealant may further be utilized with the pump(s) or an implant associated therewith to further ensure that the working fluid214does not leak out and/or mix with any of the medical contents being pumped in to the human body or critical organ. In an exemplary embodiment the sealant may be a material unaffected by the chemical properties of the working fluid214.

FIG.3depicts a cross-section view of an embodiment of a bidirectional electroosmotic pump300. It may be appreciated that the elements may be formed out of any of a variety of biocompatible materials or combinations thereof, based on implementation and use within, for example, the human body. In this figure, the working fluid314is displayed with cross-hatching. The working fluid314may include a variety of fluids based on electrical conduction properties and long-term ability to prevent bubble formation secondary to molecular electrolysis and/or repetitive conduction. Types of working fluids314may depend on the ability to be moved by electroosmosis and could include, for example deionized water, ethanol, or DMSO. In other embodiments the working fluid314may be another polar fluid compatible with the pump materials that may be used, and in some embodiments compatibility may require the working fluid314to be particle free, as particles in the working fluid314may clog the pores in the EOE, which may prevent the movement of the working fluid, which may reduce flow rate or cease pumping entirely314. In some embodiments the fluid may have a viscosity similar to water, and the fluid may be sterilized with a method compatible with the pump. For example, with ethylene oxide sterilization. The working fluid314may surround the electroosmotic element306and the electrodes308. The working fluid314, electroosmotic element306and electrodes308may all be confined within the holder312and be capped322.

FIG.4depicts a cross-sectional view of an embodiment of a bidirectional electroosmotic pump400. It may be appreciated that the parts may be formed out of any of a variety of biocompatible materials or combinations thereof, based on implementation and use. In this figure, the payload fluid420is displayed with cross-hatching. Possibilities for the payload fluid420may include a specific fluid which is time-stable and able to not degrade and remain at constant volume without evaporating or electrolyzing over time at normothermic conditions (for example, 98.6 degrees Fahrenheit). The payload fluid420may be able to flow through sub 1.5 mm channels and may include any water-based fluid or fluid with similar properties. The payload fluid420may be stable at human body temperature, have low viscosity, be compatible with any material used in the system, and/or be injectable through a device refill system. The payload fluid420may surround the inner assembly404and itself can be enclosed by the external housing416. A series of valves418may facilitate the flow of the payload fluid420in and out of the pump400. In an embodiment, the external housing416may include four valves418, two of which may direct the payload fluid420outward, two which may bring the payload fluid420in. It may be understood that other embodiments may utilize different numbers of valves and/or orientations of the valves. For example, in other embodiments, only two valves may be used, or more than four plugs may be used. Further, it may be appreciated that valves418may provide for an additional level of safety for and control of drug delivery in instances where too little or too much drug delivery can cause severe adverse events including brain injury, spinal cord paralysis, tumor recurrence, and/or patient death. Thus, in such embodiments, valves418may be monitored by some associated sensors and/or controlled such as to prevent any over- or under-delivery of medicine.

FIG.5depicts an embodiment of an implant device500that can be used to deliver medicine. It may be appreciated that the elements may be formed out of any of a variety of biocompatible materials or combinations thereof, based on implementation and use. In this embodiment, the device may contain two bidirectional pumps524in parallel connected to four exit catheters526which may extend out of the device. The pump arrangement can be reconfigured based on the device design and goals; and may contain a varying number of pumps and exit port catheters based on clinical application and/or final size requirements. Further, in the embodiment ofFIG.5, the arrangement of the bidirectional pumps524may provide for maximized multi-catheter pump flow and minimized overall footprint, thereby improving patient outcomes when implanted in the human body. Further, such an arrangement of pumps524may also mitigate risks for visible deformity status post-operatively (i.e. a visible pump on a person's head when receiving brain medicine through a pump delivery system). The pumps may be configured in a way to transmit fluid from the device. The catheters526may be formed by a flexible, biocompatible material to carry fluid from the device and to the target area. The catheters may be able to, for example, allow for 0.5-5 μl/min of fluid to pass through them. It may be understood that the number and type of the exit port can be adjusted based on need. Having multiple catheters may be advantageous over singe-catheter devices in that there is additional duplicity of medicine delivery in case a catheter blockage was to occur (i.e., with a one catheter device system a blockage formation equates to no medicine delivery versus a two catheter device system which may still continue to deliver medicine).

In an exemplary embodiment the device may also include a battery. The battery may be ideal when deemed MRI compatible in line with the rest of the device. In the embodiments, any battery or battery system may have a fixed life span, or, have a rechargeable battery system which may use wireless charging. The pump may be powered by, for example, any battery with a long enough life span, or a wirelessly rechargeable power source, both of which may deliver power to the system and contain minimal ferromagnetic materials.

In an alternative embodiment, a photo-sensing system may be an alternative method of sensing the state of the pump. The photo-sensing system may use infrared (IR) LEDs and phototransistors to sense the state of a membrane separating the working and payload fluids. An alternative shape may be utilized, for example a shape consisting of a dome made from silicone or other elastic material. The bidirectional pump may be able to utilize such an LED-phototransistor combination to detect how deformed or compressed the rubber dome is at any point in time and therefore detect the status of the pump's pumping cycle. For example, if the elastic dome is extended towards the EOE, the phototransistor may receive less IR light from the LED. Vice versa, when the dome is completely collapsed, the phototransistor may receive more IR light from the LED.

FIG.6depicts a cross-section of an exemplary embodiment of a photo-sensing mechanism600. The photo-sensing mechanism600may have an IR LED602which transmits light across the diameter of the pump assembly. Further, there may be a platinum wire604which provides a barrier for the light to pass through to fully close the light sensing circuit. The photo-sensing mechanism600may also have an IR phototransistor606that detects deformation of a rubber dome608. The rubber dome608may be dipped in another material, for example graphene, on the internal and/or external faces. In other embodiments the dome608may instead be made of fluorinated carbon-based synthetic rubber (FKM), fluorosilicone, or any other elastic material. The rubber dome608may be able to be deformed at the tip and collapse into itself. This motion may allow for an optical path between the LED602and the phototransistor606. By determining whether the path exists or is blocked the state of the bellows may be determined.

In other embodiments, as an alternative to using solid material to separate the working and payload fluids, a fluid membrane may be used. The fluid membrane may be, for example, a liquid metal, oil, or any other fluid that will not be absorbed into the working or payload fluid. This fluid membrane may achieve the same interaction as a solid barrier provided by a metal bellow or rubber dome. The fluid membrane may be moved, therefore moving the payload fluid, by, for example, being oscillated by the working fluid movement through the electroosmotic element (EOE). Oscillations of the fluid membrane may be achieved in a way that prevents any form of negative auditory feedback to the patient following human body implantation. This may be critical, for example, in embodiments where the implantable bidirectional pump sits within a skull-soft tissue temporal space in close proximity to the patient's ear.

In an exemplary embodiment the components may be bonded together using a one-part, biocompatible, room temperature vulcanizing (RTV) silicone. In other embodiments, the components may be bonded using, for example but not limited to, laser welding, spot welding, glass-metal seals, ultrasonic welding, epoxies, or UV adhesives.

In an exemplary embodiment, the bidirectional electroosmotic pump(s) may be integrated into a medical implant case. The case may be designed to match the human body shape constraints (i.e. using well accepted normative data) related to its final anatomical destination; so that it can be provided to the physician/surgeon as an “off-the-shelf” solution. This may also allow for outlet pathways to exit ports for the payload fluid to also be embedded into the medical implant case. The pump(s) may be connected by, for example, manifolds, silicone tubing, and/or fitting pieces.

FIG.7Adepicts an exemplary alternative embodiment of a bidirectional electroosmotic pump. The exemplary EOP700design may have one or more electrodes702that may power the EOP700. The one or more electrodes702may be made of, for example, platinum. The EOP700may further have an EOP bellows housing704which may further have an outer housing706and an inner housing708. The bellow housing704, outer housing706, and inner housing708may be made of, for example, titanium, another metal, polyphenylene sulfide (PPS), other plastics, other polymers, and/or any other materials known in the art. In some embodiments the outer housing706and the inner housing708may be made of the same material while in others they may be made of different material. The inner housing708and outer housing706may be connected through, for example, welding, ultrasonic welding, or an adhesive. The EOP700may further have an EOE housing710. The EOE housing710may be connected to the bellows housing704by a connector712. The EOE housing710may be made of, for example, polymers, titanium, another metal, glass, and/or ceramics. A working fluid764may further be contained in the EOE housing710. It may be understood that the working fluid may be able to move between the EOE housing710and the EOP bellows housing704via the connector712. The EOP700may further be connected to a pump management printed circuit board (PCB)714which may be connected to and control the electrodes702and/or to bellows sensing wires726.

FIG.7Bdepicts a cross-sectional view720of the exemplary alternative embodiment of the EOP700. Within the EOE housing710there may be an electroosmotic element722. The electrodes702may be attached to the electroosmotic element through, for example, insert molding to pass electric charge to the electroosmotic element face, which may be, for example, platinum paste. The electroosmotic element722may be a material such as ceramic, that when voltage is applied to the electroosmotic element722through the electrodes702the working fluid764is moved. The electroosmotic element722may be porous, which may enable the working fluid to flow through, causing the electroosmotic effect that drives the bidirectional electroosmotic pump. In an exemplary embodiment, the electroosmotic element722may be, for example, a porous ceramic body. In other embodiments, the electroosmotic element722may be other materials, including but not limited to various dielectrics such as sintered glass, silica, and/or alumina. When the voltage being applied to the electrodes702is alternated between a first polarity and a second opposite polarity, a reciprocating fluid motion may be generated through the movement of the working fluid764. This movement may help control movement of bellows724, for example by moving via the connector712into one or more working fluid chambers728. The bellows724may be, for example, a titanium foil that is formed into a dome shape and deforms under pressure. The bellows724may be connected to the EOP bellows housing via, for example, welding. The movement of the bellows724may be detected and recorded by one or more bellows sensors726which may be contained within one or more of the working fluid chambers728and/or payload fluid chambers730. The bellows sensors726may be attached using, for example, epoxy. The bellows sensors726may be electrodes and may work by, for example, sensing an electrical connection created when the bellows724deform and contact the bellows sensors726. When the bellows sensors726sense such a connection or otherwise determine that the bellows have been deformed, the electrodes702may switch polarity to the opposite polarity, which may begin a new pumping cycle.

FIGS.7C and7Ddepict an exemplary inner assembly740of the electroosmotic element housing710for the exemplary alternative embodiment of the bidirectional electroosmotic pump700.

FIGS.7E and7Fdepict an interior view of the exemplary alternative embodiment of the bidirectional electroosmotic pump760. Initially, the payload chamber730may be filled with a payload fluid762, where the payload fluid762may be, for example, saline, an MRI tracer such as gadolinium, a medication such as topotecan, another medication known to be a safe and effective anti-tumor medicine in the setting of high grade glioma, or another fluid with clinical benefits known in the art. In some embodiments, the payload fluid may be a combination of fluids, for example, an MRI tracer and a medication, or two or more medications, where the fluids are compatible with each other. As electroosmosis is used to move the working fluid764, the one or more working fluid chambers728may be filled, causing the bellows in the payload chamber730to restrict and expand, thereby pushing some of the payload fluid762out to be delivered.

FIG.7Gdepicts an EOP assembly utilizing the exemplary alternative embodiment of the EOP780. The EOP700may be connected with one or more check valves782via one or more joints784. The one or more joints784may facilitate movement of the payload fluid762to the check valves782. In an exemplary embodiment, as the reciprocating motion of the bellows intakes the payload fluid762, the check valves782may allow fluid to pass through from the reservoir and the outlet valves may help prevent backflow. Backflow would be dangerous in instances of medicine reflux, and therefore, may be avoided using a valve-assisted design such as this. When the bellows724expel the payload fluid762the inlet valve may prevent backflow while the outlet valve dispenses the payload fluid762, for example, through one or more catheters.

FIG.8depicts an exemplary method for using a bidirectional electroosmotic pump800. For the sake of example, the method will be shown with reference to the bidirectional electroosmotic pump700described inFIGS.7A-7G, however, in other embodiments the method800may be used with other electroosmotic pumps such as those described above, or other embodiments not described herein. In a first step802, the working fluid764may be moved from the electroosmotic element housing710to the bellows assembly704by applying a first polarity electric potential to the one or more electrodes702. This may cause the bellows742to deform as the working fluid764begins to fill the one or more working fluid chambers728. In a second step804the deformation of the bellows742may be sensed by the one or more bellows sensors726and communicated to other systems via the pump management PCB714.

In a third step806the working fluid764may be moved back to the electroosmotic housing710from the bellows assembly704by switching the polarity of the electric potential being applied to the one or more electrodes702to the opposite polarity. The switch may be done automatically based on the sensing mechanism described in step804. In a fourth step808, steps802-806may be repeated periodically in order to create a reciprocating movement of the working fluid764, which may allow the bellows742to move at a continuous rate. The periodic rate may be based on the sensing mechanism, and the sensing mechanism may have a programmable delay to control the switching time span. In a final step810, the payload fluid762may be dispensed from the bidirectional electroosmotic pump based on the movement of the bellows. By using an embedded software technology platform, the time interval of each sensing mechanism and pump adjustment may be adjusted wirelessly and remotely at any timepoint; thereby changing hourly, daily, weekly, monthly, and/or yearly quantities of medicine delivery through different instantaneous active flow rates, average flow rates based on swept volume, and/or infusion schedules. In an exemplary embodiment the pump may have a mirrored design which causes the sides of the pump to alternate which step ofFIG.8they are on. For example, if the first pump is on step802the second half of the pump may simultaneously be on step806.

The foregoing description and accompanying figures illustrate the principles, preferred embodiments and modes of operation of the invention. However, the invention should not be construed as being limited to the particular embodiments discussed above. Additional variations of the embodiments discussed above will be appreciated by those skilled in the art. Additionally it may be understood that parts or aspects described in one embodiment may likewise be used in other embodiments where appropriate.

Therefore, the above-described embodiments should be regarded as illustrative rather than restrictive. Accordingly, it should be appreciated that variations to those embodiments can be made by those skilled in the art without departing from the scope of the invention as defined by the following claims.