Biocompatible wireless microelectronic

Abstract

The disclosed technology herein relates to a self-assembled microtubular pacemaker for wireless and leadless myocardial stimulation. The pacemaker includes a flexible printed circuit board (f-PCB) disposed between an adhesive first layer and an adhesive second layer. The f- PCB, the first layer, and the second layer are assembled in a tubular structure. The f-PCB includes a transmitter and a pair of electrodes operably coupled to one another via a circuit of the f-PCB. The transmitter is configured to control a wireless power transfer of energy to the electrodes.

Description

BIOCOMPATIBLE WIRELESS MICROELECTRONICCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to US Provisional Patent Application No. 63 / 653,438, filed on May 30, 2025, incorporated herein by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

[0002] This invention was made with government support under NIH HL149808 and NIH HL118650 awarded by National Institutes of Health; and under VA 101 BX004356 awarded by the Department of Veteran Affairs. The government has certain rights in the invention.BACKGROUND

[0003] Microstimulators are implanted cardiac, gastric, neural, and urological devices to sustain life. With respect to cardiac devices, more than half a million U.S. patients have implantable pacemakers. Additionally, pacemakers are becoming more prevalent rising from 0.4 per 1000 among persons ages 18 to 64 to 26 per 1000 among those ages 75 or older. However, pacing leads (e.g., electrodes) of conventional pacemakers are prone to dislodge, fracture, and develop insulation defects as a substrate for biofilm formation. The number of incidents related to pacing lead complications has reached -11%. Further, the rate of pacemaker casing-related complications, including infection, device erosion into the tissue, and hematoma, is estimated to be 8% at 5 years.

[0004] Currently, leadless pacemakers have been developed to address the complications from pacing leads. One such pacemaker is a leadless cardiac stimulation device with a minimally invasive delivery to the right ventricle. However, this pacemaker includes an integrated battery that introduces new clinical challenges, such as device implantation, perforation through the myocardium, and dislodgement. Moreover, the current device is limited to single-chamber pacing.

[0005] Further, typical flexible and self-powered devices using different energy harvesting mechanisms may provide battery -free operation mode. However, as these devices may only provide suboptimal operational stability and output power, self-powered pacing devices have remained at the investigational stage. Alternatively, wireless power transmission, includingmagnetic induction, radio frequency (RF), and ultrasound, represents a viable strategy to charge the pacemakers in vivo. However, open-chest surgery (e.g., thoracotomy) is required to implant the bioelectronic patches of these wireless implantable electronics onto the epicardium (i.e., surface of the heart).

[0006] Advances in vascular catheter-based deployment allow for implantation of biomedical devices, such as arterial stents and bioprosthetic valves. Through a percutaneous incision to the femoral or radial arteries, catheter-based deployment obviates the need for thoracotomy for cardiac bypass surgery or valve replacement and shortens recovery times and hospital stay. Recently, artificial stent and electric blood vessels enable a small and implantable endovascular device for targeted control for localized therapy. However, the primary challenge resides in the development of battery-free and implantable pacemakers with miniaturized electronics for efficient power transfer and minimal power absorption over an anatomically wireless range.

[0007] Thus, there is a need in the art for a leadless and battery-free pacemaker that may be implanted with a minimally invasive procedure. The present invention satisfies this need.SUMMARY

[0008] The present disclosure relates generally to implantable electronics, and more particularly, to a microtubular pacemaker for wireless cardiac electrotherapy.

[0009] In one or more aspects, the disclosed technology provides a self-assembled microtubular pacemaker for wireless and leadless myocardial stimulation. In one or more cases, the pacemaker includes a flexible printed circuit board (f-PCB) disposed between an adhesive first layer and an adhesive second layer. In one or more cases, the f-PCB, the first layer, and the second layer are assembled in a tubular structure. In one or more cases, the f-PCB includes a transmitter and a pair of electrodes operably coupled to one another via a circuit of the f-PCB. In one or more cases, the transmitter is configured to control a wireless power transfer of energy to the electrodes.

[0010] In one or more aspects, the disclosed technology provides a tubular implantable device that facilitates intravascular implantation in an organ. In one or more cases, the device includes a first adhesive polymer layer and a second adhesive polymer layer disposed on opposing sides of a flexible printed circuit board (f-PCB) and shaped into a tubular structure. In one or more cases, the device includes a guidewire, a portion of which is positioned within the tubular structure ofthe implantable device. The f-PCB includes a transmitter and a pair of electrodes operably coupled to one another via a circuit of the f-PCB. The transmitter is configured to control a wireless power transfer of energy to the electrodes.

[0011] A variety of additional aspects will be set forth in the description that follows. The aspects can relate to individual features and to combination of features. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the broad inventive concepts upon which the embodiments disclosed herein are based.BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The following drawings are illustrative of particular embodiments of the present disclosure and therefore do not limit the scope of the present disclosure. The drawings are not to scale and are intended for use in conjunction with the explanations in the following detailed description.

[0013] FIG. 1 illustrates an exploded view of an example of a pacemaker.

[0014] FIG. 2A illustrates a perspective view of the example pacemaker of FIG. 1 in an unassembled state.

[0015] FIG. 2B illustrates a perspective view of the example pacemaker of FIG. 2A being assembled.

[0016] FIG. 2C illustrates a perspective view of the example pacemaker of FIG. 2A in an assembled state including an example guidewire.

[0017] FIG. 2D illustrates a cross-sectional view of the example pacemaker in the assembled state, and FIG. 2E illustrates an enlarged molecular view of the example pacemaker in the assembled state.

[0018] FIG. 3 illustrates an example circuit diagram of an example electrotherapy system.

[0019] FIG. 4A illustrates an example operational diagram of the example electrotherapy system of FIG. 3. FIG. 4B illustrates an example portable module with an RF transmitter and ECG porting.

[0020] FIG. 5 illustrates an example implantation of the example pacemaker.

[0021] FIG. 6 is a schematic diagram illustrating example effects of displacement, misalignment, and angular misalignment on power transferring efficiency (PTE).

[0022] FIG. 7A illustrates example simulations of magnetic fields at various radii of an example transmitter coil. FIG. 7B illustrates simulation results for the magnetic fields of the transmitter coil.

[0023] FIG. 8 A illustrates an example coupling efficiency as a function of a radius of the coil. FIG. 8B illustrates an example correlation in PTE as a function of horizontal misalignment between a transverse direction and a longitudinal direction. FIG. 8C illustrates an example correlation in PTE as a function of angular misalignment between axial rotation and tilting.

[0024] FIGs. 9A-9L illustrate example electrical characterizations and cytotoxicity assay of the example microtubular pacemaker.

[0025] FIGs. 10A-10F illustrate an example intravascular implantation of the example microtubular pacemaker to restore cardiac conduction and myocardial contraction.

[0026] FIGs. 11A-1 IF illustrate an example intravascular implantation of the example microtubular pacemaker to restore hemodynamic blood flow.DETAILED DESCRIPTION

[0027] The following discussion omits or only briefly describes conventional features of implants that are apparent to those skilled in the art. It is noted that various embodiments are described in detail with reference to the drawings, in which like reference numerals represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the claims attached hereto. Additionally, any examples set forth in this specification are intended to be non-limiting and merely set forth some of the many possible embodiments for the appended claims. Further, particular features described herein can be used in combination with other described features in each of the various possible combinations and permutations.

[0028] Unless otherwise specifically defined herein, all terms are to be given their broadest reasonable interpretation including meanings implied from the specification as well as meanings understood by those skilled in the art and / or as defined in dictionaries, treatises, etc. It is noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless otherwise specified, and that the terms “includes” and / or “including,” when used in this specification, specify the presence of stated features, elements,and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0029] Relative terms such as “horizontal,” “vertical,” “up,” “down,” “top,” and “bottom” as well as derivatives thereof (e.g., “horizontally,” “downwardly,” “upwardly,” etc.) should be construed to refer to the orientation as then described or as shown in the drawing figure under discussion. These relative terms are for convenience of description and normally are not intended to require a particular orientation. Terms including “inwardly” versus “outwardly,” “longitudinal” versus “lateral” and the like are to be interpreted relative to one another or relative to an axis of elongation, or an axis or center of rotation, as appropriate. Terms concerning attachments, coupling and the like, such as “connected” and “interconnected,” refer to a relationship wherein structures are secured or attached to one another either directly or indirectly through intervening structures, as well as both movable or rigid attachments or relationships, unless expressly described otherwise. The term “operatively or operably connected” is such an attachment, coupling or connection that allows the pertinent structures to operate as intended by virtue of that relationship.

[0030] Reference throughout the specification to “one embodiment”, “an embodiment” or “some embodiments” means that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment of the subject matter disclosed. Thus, the appearance of the phrases “in one embodiment”, “in an embodiment” or “in some embodiments” in various places throughout the specification is not necessarily referring to the same embodiment. Further, the particular features, structures or characteristics of “one embodiment”, “an embodiment” or “some embodiments” may be combined in any suitable manner with each other to form additional embodiments of such combinations. It is intended that embodiments of the disclosed subject matter cover modifications and variations thereof. Terms such as “first,” “second,” “third,” etc., merely identify one of a number of portions, components, steps, operations, functions, and / or points of reference as disclosed herein, and likewise do not necessarily limit embodiments of the present disclosure to any particular configuration or orientation.

[0031] Moreover, throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope ofthe invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, 6, and any whole and partial increments there between. This applies regardless of the breadth of the range. As used herein, the term “about” in reference to a measurable value, such as an amount, a temporal duration, and the like, is meant to encompass the specified value and / or variations of plus or minus 20%, plus or minus 10%, plus or minus 5%, plus or minus 1%, and plus or minus 0.1% of the specified value, as such variations are appropriate.

[0032] The terms “proximal,” “distal,” “anterior,” “posterior,” “medial,” “lateral,” “superior,” and “inferior” are defined by their standard usage indicating a directional term of reference. For example, “proximal” refers to a position that is situated nearer to the center of a body or point of attachment, while “distal” refers to a position that is situated away from the center of the body or point of attachment. In another example, “anterior” refers to the front of a body or structure, while “posterior” refers to the rear of a body or structure. In another example, “medial” refers to the direction towards the midline of a body or structure, and “lateral” refers to the direction away from the midline of a body or structure. In some examples, “lateral” or “laterally” may refer to any sideways direction. In another example, “superior” refers to the top of a body or structure, while “inferior” refers to the bottom of a body or structure. It should be understood, however, that the directional term of reference may be interpreted within the context of a specific body or structure, such that a directional term referring to a location in the context of the reference body or structure may remain consistent as the orientation of the body or structure changes.

[0033] The terms “patient,” “subject,” “individual,” and the like are used interchangeably herein, and refer to any animal amenable to the systems, devices, and methods described herein. The patient, subject or individual may be a mammal, for example, a human.

[0034] Conventional cardiac pacemakers are implanted via open-chest surgery, which is invasive and requires prolonged wound healing and causes other healthcare burdens. Moreover, the pacing leads of these pacemakers are prone to introduce valve damage and infection. Further, as these pacemakers are battery dependent and are included within the pacemaker, when the battery needs to be replaced, the complete pacemaker needs to be retrieved to replace the battery. Theembodiments described herein provide a self-assembled implantable micro-tubular pacemaker that is lightweight and wireless, providing high electrical output and operational stability for intravascular myocardial pacing and mechanical coupling. The embodiments describe a microtubular pacemaker configured to reduce the mechanical burden due to device fixation to the myocardium and pacing lead-related medical complications. In one or more cases, a wireless RF module is embedded in a thin flexible polyimide membrane for receiving power transfer from the external transmitter. The polyimide membrane is selectively encapsulated with an elastomer layer to insulate the circuits. This encapsulation provides the adhesive property for the rolling self-assembly process into the microtubular pacemaker for intravascular deployment and implantation. To optimize power transfer efficiency to the microtubular pacemaker, a portable RF power transmitter is configured to provide the DC pulse delivery up to 5 V to the bipolar electrode (anode and cathode) for electrical stimulation. Embodiments of a self-assembled microtubular pacemaker for wireless and leadless myocardial stimulation are described below with reference to the Figures.

[0035] FIG. 1 illustrates an exploded view of an example pacemaker 100. FIG. 2A illustrates a perspective view of the pacemaker 100 in an unassembled state. FIG. 2B illustrates a perspective view of the pacemaker 100 being assembled. FIG. 2C illustrates a perspective view of the pacemaker 100 in an assembled state including an example guidewire 220. The pacemaker 100 may be tailored to, for example, but not limited to, cardiovascular anatomy and electrophysiology for wireless and battery-free stimulation; however, it should be understood that the pacemaker 100 may be tailored to stimulate other anatomical parts. In some cases, in an assembled state, the pacemaker 100 may have a width ranging from about 2 mm to 5 mm and a length ranging from about 10 mm to 30 mm. For example, in an assembled state, the pacemaker 100 may have a thickness of about 80 pm, a length of about 20 mm, and a width of about 2.5 mm. The pacemaker 100 may include a plurality of layers, such as, but not limited to, a first layer 102, a printed circuit board (PCB) layer 103, and a second layer 110.

[0036] The first layer 102 may be, for example, but not limited to, a styrene-ethylene-butylene- styrene (SEBS) polymer layer, and other block copolymers, such as Styrene Isoprene Styrene (SIS). The first layer 102 may be applied to a side of the PCB layer 103 that interfaces with the first layer 102. The first layer 102 may be applied to the PCB layer 103 via a mask-spraying method or another like method. The first layer 102 may provide a resistance to water. The secondlayer 110 may include one or more of the same or similar features as the first layer 102, and a description of such features is not repeated herein. The second layer 110 may be applied to a side opposite the side of the PCB layer 103 that includes the first layer 102. As such, the first layer 102 and the second layer 110 may encapsulate the PCB layer 103 as illustrated in FIG. 2D. By encapsulating the PCB layer 103, the first layer 102 and second layer 110 may insulate the PCB layer 103 from corrosion in an electrolyte-rich environment and provide long-term operational stability for the pacemaker 100. In one or more cases, the first layer 102 and second layer 110 may provide self-adhesive properties for the self-assembly rolling process to form a stable microtubular structure, as illustrated in FIGs. 2D and 2E.

[0037] The PCB layer 103 may be a flexible PCB that includes a plurality of modules, such as an antenna 104, a circuit 105, and electrodes 108 disposed on a polymide film 106. The antenna 104 may include a pair of antennas 204a and 204b configured to receive a signal (e.g., radio frequency (RF) energy) from an external transmitter. The antenna 104 may be electrically coupled to the circuit 105, via, for example, one or more foot pins. The circuit 105 may be, for example, a rectifier circuit. The circuit 105 may include a voltage doubler unit. The circuit 105 may be configured to convert AC waveforms to DC pulses. The electrodes 108 may be, for example, anode electrodes 210 and cathode electrodes 208 configured to deliver DC pulses. The electrodes may be used to provide stimulation. For example, the DC pulses provided by the anode electrodes 210 and cathode electrodes 208 may be used for myocardial stimulation. In one or more cases, the cathode electrodes 208 are configured to maintain an optimal current density of electron streams. As such, the cathode electrodes 208 may reduce the power consumption used for cardiac stimulation. In one or more cases, when being assembled on the polyimide film 106, the electrodes 108 may be sputtered with a layer of gold to provide electrochemical stability in an electrolyte-rich environment.

[0038] The pacemaker 100 may be defined, for example, by sides 212, 214, 216, and 218. Sides 214 and 218 may form the top and bottom of the assembled pacemaker 100. Sides 212 and 216 may define a length of the assembled pacemaker 100. To assemble the pacemaker 100, the pacemaker 100 is rolled from an unassembled state, such as the planar shape illustrated in FIG. 2A, into a tubular shape as illustrated in FIG. 2C. For example, as illustrated in FIG. 2B, side 212 may be rolled in direction A towards side 216. The adhesive properties of the first layer 102 and the second layer 110 allow one or both of the first layer 102 and second layer 110 to adhere toone another as the pacemaker 100 is configured into the assembled state. Thus, the first layer 102 and the second layer 110 allow the pacemaker 100 to maintain a tubular shape in the assembled state. The tubular shape (e.g., a microtubular shape) of the pacemaker 100 facilitates intravascular implantation into, for example, but not limited to, the ACV.

[0039] In one or more cases, a guidewire 220 may be used to implant the tubular shaped pacemaker 100 into, for example, but not limited to, the anterior cardiac vein (ACV) of a heart, such as the ACV 502 of heart 500 illustrated in FIG. 5. For example, the guidewire 200 may facilitate intravascular deployment, similar to catheter-based deployment of cardiac stents. The guidewire 220 may be positioned within the assembled pacemaker 100, as illustrated in FIG. 2C. In one or more cases, the guidewire 200 is positioned within the hollow structure of the assembled pacemaker 100 after the pacemaker 100 is configured in an assembled state. In one or more cases, the guidewire 200 is positioned on a planar surface of the pacemaker 100 in an unassembled state, and the pacemaker 100 is subsequently positioned in the assembled state. For example, the pacemaker 100 may be rolled around the guidewire 200 and into the assembled state. In one or more cases, the pacemaker 100 may include a hoop on an end, such as sides 214 or 216, of the pacemaker 100. A catheter or a similar device may couple with the hoop, such that the catheter may retrieve the pacemaker 100, for example, from a deployed position within a heart.

[0040] The antennas 204a and 204b may form a transmitter 202 configured to control a power transfer of RF energy (e.g., the RF energy 506 provided to pacemaker 100 illustrated in FIG. 5) to the microtubular electronics. The transmitter 202 may be, for example, a portable RF transmitter, 304. The transmitter 202 may include, for example, but not limited to, a class D push-pull amplifier and a microcontrol unit (MCU) configured to optimize the coupling of inductive power to the receiver coils.

[0041] FIG. 3 illustrates a circuit diagram of the portable RF transmitter 304 and the implantable pacemaker 302, and FIG. 4A illustrates an operational diagram of the wireless intravascular pacing system, in which the external transmitter device generates inductive power transfer to the receiver coils of the pacemaker 100 for electrical stimulation. FIG. 4B illustrates a portable module with an RF transmitter and ECG porting that is configured to optimize inductive power transferring to the receiver. The integrated circuit 302 of the microtubular electronics (e.g., the pacemaker 100) enables the resonant capacitor 306 to receive the AC waveforms from theexternal transmitter coil 202. The AC waveforms may be converted to rectified DC pulses, via the AD-DC converter 308, and delivered to the anode and cathode electrodes 208 and 210. The portable transmitter circuit 304 may provide a monopolar pulse voltage ranging from 0 to 5 V to control the duration and period of the RF waveform group. The RF signal (FRF) may be applied to the gate of an n-type metal oxi de-semi conductor field-effect transistor and then fed to the class D RF amplifier 304, as illustrated in FIG. 4B. The inductance LI of the transmitter coil 202 may be resonantly coupled with a capacitor Cl in series, thereby enabling the alternative and efficient induction of magnetic field to the receiver coils. The inductance L2 of the receiver antenna may be resonantly coupled with a capacitor C2, via resonant tank 306. A voltage doubler unit, such as the AD-DC converter 308, may rectify the RF AC signals to DC pulses. The DC energy may be stored in the capacitor C3, which filters the overlapped ripples before delivering the DC pulses (e.g., DC pulses 504 illustrated in FIG. 5) to the cathode and anode electrodes 208 and 210 to, for example, stimulate the heart (e.g., heart 500 of FIG. 5).

[0042] In one or more cases, to determine the optimal power transferring efficiency (PTE), the magnitude of the magnetic field radiated from the transmitter coil to the receiver coil was simulated using ANSYS software. FIG. 6 is a schematic diagram illustrating the example effects of displacement, misalignment (e.g., in a transverse direction and a longitudinal direction), and angular misalignment on PTE. The maximum strength of the magnetic field occurred in the region most proximal to the transmitter coil 202. As the displacement increased, the magnetic field for the central point declined proportionally to the reciprocal of the radius. In the normal direction, the magnetic field was highly related to the radius of the coil and the displacement to the transmitter coil plane. While a small transmitter radius may result in an insufficient magnetic field to the out-of-plane point, a large radius may lead to the out-of plane point too far to achieve sufficient magnetic field. FIG. 7A illustrates example simulations of magnetic fields at various radii of the transmitter coil 202. As illustrated in example simulations B 1 to B4 in FIG. 7A, the three-dimensional (3D) model for the transmitter coil 202 in ANSYS used copper wires configured into a two-layer hexagon with a span of 1.0 cm and six turns. As the outer radius increased from 20 to 32 mm, the distribution of the magnetic field was enlarged from 20 to 30 mm beyond the transmitter coil plane, as illustrated in FIG. 7B. FIG. 7B illustrates simulation results for the magnetic fields of the transmitter coil. The magnetic fields were simulated at 20 mm and 32 mm radius of the transmitter coil. FIG. 8 A illustrates an example coupling efficiencyas a function of a radius of the coil 202. As illustrated in FIG. 8 A, at a displacement of 20 mm, the maximal coupling efficiency was achieved at the outer radius of 24 mm or about 24 mm; and at a displacement of 30 mm, the maximal efficiency was achieved at the radius of 28 mm or about 28 mm. Further, the coupling efficiency at a displacement of 20mm increased by more than twofold as compared to that of 30 mm, from 0.44 to 1.35%. Therefore, the magnetic field simulation enhanced the design of the hexagonal transmitter coil to optimize the coupling efficiency.

[0043] Myocardial contraction generates a periodical misalignment around the original position during a cardiac cycle. As such, alignment of the transmitter and receiver coil influences the efficiency in inductive powering transferring. The impact of misalignment on PTE was investigated. FIG. 8B illustrates an example correlation in PTE as a function of horizontal misalignment between a transverse direction and a longitudinal direction. As illustrated in FIG. 8B, a horizontal misalignment from 0 mm to 10 mm in the transverse direction or the longitudinal direction resulted in a reduction in PTE by >50%, therefore demonstrating that the strength of the magnetic field in the region off the normal direction to the transmitter coil decayed rapidly. FIG. 8C illustrates an example correlation in PTE as a function of angular misalignment between axial rotation and tilting. As illustrated in FIG. 8C, angular misalignment via axial rotation or lateral rotation to a 30° resulted in a small reduction in PTE by -10%.

[0044] Before implanting the microtubular pacemaker 100 for cardiac pacing, the strength of the inductively powered system was characterized via in vitro testing. FIGs. 9A-9H illustrate example electrical characterizations and cytotoxicity assay of the pacemaker 100. FIG. 9A illustrates that in the transmitter unit, the RF amplifier increased the amplitude of VRF signals to the transmitter coil. FIG. 9B illustrates that a single stimulation pulse signal delivered a rapid rise and decay in voltage to the anode and cathode. As illustrated in FIGs. 9A and 9B, the initiation and termination of the RF pulses were coupled with rise and fall of the DC pulses.

[0045] FIG. 9C illustrates that rectification was achieved via a voltage doubler to deliver the DC pulses to the anode and cathode. The voltage of the DC pulse was dependent on the strength of the magnetic field, which decayed rapidly as the displacement increased from 0 to 3.0 cm. As illustrated in FIG. 9C, two circuit architecture was used to compare RF / AC-DC conversion with the voltage doubler versus full bridge rectifier (as illustrated in FIG. 91). FIG. 91 illustrates an example electrical output of the full bridge rectifier. As illustrated in FIG. 91, the voltage of theDC pulse was dependent on the strength of the magnetic field, which decayed rapidly as the displacement increased from 0 cm to 3.0 cm. In the transmitter unit, the RF amplifier gradually increased the transmission power voltage from 5.0 to 12.0 V to the receiver coil. In the stimulation unit, the voltage of the DC pulse was rectified and delivered to the anode and cathode. As the displacement between the transmitter coil and receiver coil increased from 0.5 to 3.0 cm, the coupling efficiency declined, resulting in a decrease in the voltage of DC pulse. By increasing the operating voltage of the transmitter, the DC pulse may be reliably maintained above 2 V, even when the distance between the transmitter and pacemaker exceeds 3 cm (as illustrated in FIG. 9J). FIG. 9J illustrates an electrical output of the pacemaker, in which the relationship between voltage of the DC pulse and RF transfer distance when the operating voltage (VDD) is set at 14V. This ensures that the pacemaker fulfills the requirements for patients with greater chest-to-skin distances. The voltage doubler excited the electrons to a higher potential to double the amplitude of the RF / AC signal, leading to additional increase in the voltage of the DC pulses for cardiac stimulation. Thus, the voltage for the DC pulse generated from the pacemaker 100 provides sufficient energy threshold to reenergize the nonbeating heart in the euthanized pig, as illustrated in FIGs. 10A-10F.

[0046] Electrical impedance spectroscopy was performed to evaluate the electrical impedance (ohm) and phase (0) of the stimulating electrodes over a frequency range (0.1 Hz to 1 MHz) (Fig. 3D). FIG. 9D illustrates representative impedance and phase-angle spectra of the stimulating electrodes that were sputtered with a gold (Au) layer. The impedance of the Au-sputtered stimulating electrodes was maintained at ~110 ohms until the frequency was lower than 100 Hz in the phosphate-buffered saline (PBS) solution. The phase plot of the impedance spectrum revealed a phase angle close to 0° when the frequency was above 100 Hz. The electrical impedance spectroscopy performance supports the dominance of the resistance component suitable for electrophysiological simulations. FIG. 9D illustrates cyclic voltammograms of a representative stimulation electrode at the 1st, 5th, 20th, and 50thcycles in PBS solution. As illustrated in FIG. 9D, the voltammogram cycles showed a wide bandwidth of electrochemical stability of the Au-sputtered stimulating electrodes from a linear voltage sweep in PBS (-0.6 to 0.6 V). The voltammogram demonstrates a reliable electrochemical stability under the physiological conditions. The microtubular electronics were assessed for long-term stability. FIG. 9F illustrates a change in impedance at the frequency of 1, 100, and 1000 Hz of thestimulation electrode over 96-hour immersion in the PBS solution. As illustrated in FIG. 9F, the impedance magnitude of an individual stimulating electrode remained stable over the 96-hour immersion in PBS.

[0047] The microtubular electronics were tested for biocompatibility as described herein. To evaluate the biocompatibility of the materials, an in vitro incubation assay was performed using the human peripheral blood mononuclear cells (PBMCs) as a well-accepted immune cell population for investigating biocompatibility and inflammatory responses to various materials. By virtue of PBMC’s heterogeneous population, consisting of granulocytes, monocytes, and lymphocytes (i.e., natural killer cells, T cells, and B cells), these cells actively participate in both inflammatory and immune responses. PBMCs were incubated with the materials used in the pacemaker 100, including the Au electrodes, polyimide, and SEBS polymer. Flow cytometry (i.e., fluorescence-activated cell sorting (FACS)) analysis was performed to evaluate the viable cell population, including the total cells, monocytes, granulocytes, T cells, B cells, and natural killer cells, as illustrated in FIG. 9G. FIG. 9H illustrates a plot of various immune cell numbers over time that indicates that the device imparted minimal cytotoxic effects on activation of various immune cell populations. As illustrated in FIG. 9H, cell counts and fluorescence-activate cell sorting (FACS) analyses (as illustrated in FIG. 9K) indicated the absence of cell toxicity and immune responses for up to 7 days. FIG. 9K illustrates live cells, including monocytes, granulocytes, T cells, B cells, and natural killer cells, on day 3. The same gating method was applied to data collected on day 0, day 3, and day 7, enabling monitoring of changes in cell populations over time. This result demonstrates that no discernible changes of major immune cell population (B-cells, T-cells, natural killer cells, monocytes, and granulocytes) in response to the device’s materials, and the total cell apoptosis rates remains consistent regardless of the presence or absence of the device’s constituent materials, suggesting the pacemaker does not induce substantial chronic immune toxicities or cytotoxicity. Microscopic examination of the cultured cells further revealed similar cell densities in response to the materials used in the pacemaker 100, consistent with those of FACS analysis.

[0048] To further demonstrate hemocompatibility, a series of ex vivo experiments were conducted to observe thrombotic responses. FIG. 9L illustrates heparinized v. non-heparinized mouse blood and the thrombus v. no thrombus formation around the pacemaker. Sample A of non-heparinized blood illustrates a blood clot formed in the non-heparinized blood after it wasextracted from a mouse for 10 minutes. Sample B of heparinized blood illustrates blood clots were absent in the heparinized blood after it was extracted from a mouse for 10 minutes. Sample C of non-heparinized blood illustrates a blood clot formed around the pacemaker in the nonheparinized blood. Sample D of non-heparinized blood illustrates blood clot formation around the pacemaker was absent in the heparinized blood. As shown in FIG. 9L, in the absence of heparin, the blood forms clots in both test and control groups as evidenced by the nonhomogeneous appearance. In the presence of heparinization, the blood appears homogeneous in coloration in these groups. Collectively, these experiments demonstrated the biocompatible materials used in the microtubular pacemaker.

[0049] Intravascular pacing to restore electromechanical coupling and blood circulation was demonstrated as further described herein. The porcine whole-heart models closely resemble human physiology and are clinically translational for in vivo studies. Here, in vivo implantation in a Yorkshire pig demonstrated how this microtubular, leadless, and battery -free pacemaker is capable of delivering electrical stimulation up to DC of 5 V. To provide continuous pulse transfer to the implanted pacemaker, a portable system was developed to combine an RF transmitter and an MCU to achieve wireless power delivery and ECG data acquisition.

[0050] FIG. 10A is a schematic of the portable system that combined an RF transmitter and an MCU to achieve wireless power delivery and ECG data acquisition. To acquire the ECG signal from the heart, the pacemaker 100 to the ACV in a Yorkshire pig immediately after euthanasia in compliance with the Institutional Animal Care and Use Committee (IACUC). FIG. 10B illustrates intravascular implantation of the pacemaker 100 to the anterior vein of a non-beating heart, and induction of the transmitter coil for magnetic interaction with the receiver coil. An experienced veterinarian performed a thoracotomy to provide the surgical window of the epicardium of the pig heart and to allow for dissection and isolation of one of the ACVs for intravascular implantation of the microtubular pacemaker. The stimulating electrodes of the pacemaker 100 achieved intimate contact with the walls of the selected cardiac vein. This ensured that electrical stimulation can be effectively delivered into the heart while also preventing pacemaker slippage along the vein. ACV was chosen for its proximity to the chest wall as the ideal region for optimal inductive power transfer and for its proximity to His-Purkinje fiber (i.e., the conduction bundle) for generation of the narrow QRS complex (as opposed to the wide QRS complex associated with ventricular pacing). As illustrated in FIG. 10C, the RFtransmitter coil was placed above the epicardium where the pacemaker 100 was implanted to the ACV in an anesthetized pig. The ECG leads were connected to the left upper limb, right upper limb, and the left hindlimb of the animal for real-time recording in response to inductive power transfer and myocardial stimulation.

[0051] Intravenous implantation of the pacemaker 100 to reenergize electrical conduction and myocardial contraction was set at 1 Hz (i.e., 60 beats / min (bpm)) at a pulse duration of 1 ms. The pacemaker 100 was implanted to the cardiac anterior vein, and the RF transmitter coil was positioned at ~2.0 to 3.0 cm above the receiver coils, as illustrated in FIGs. 10B and 10C. In response to the wireless power transmission, the surface ECG recorded real-time cardiac conduction before and after the stimulation spikes, as illustrated in FIG. 10D. FIG 10D i) illustrates the implantation of the pacemaker 100 in the ACV. FIG. 10D ii) illustrates that the displacement between external transmitter (i.e., the white dashed box) and the pacemaker 100 was greater than 20 mm for inductive power transferring. The ECG waveform was flat before stimulation, and upon inductive power transfer, the ECG demonstrated QRS complexes and T waves at 60 bpm. After removal of the transmitter coil, the ECG returned to a flat line. FIG. 10D iii) illustrates that a myocardial contraction was recorded by the video tracking (as illustrated in FIG. 10E) of an epicardial region of the left ventricle demonstrating the electrical and mechanical coupling in response to intravascular pacing. The contraction region was labeled, and the moving coordinates around the center of the region were calibrated to synchronize with the ECG. For example, as illustrated in FIG. 10F, an ECG rhythm strip revealed the initiation of electrical stimulation in the non-beating heart at 60 bpm as evidenced by the consistent pacing spikes, followed by QRS for myocardial activation and T waves for repolarizations (inset). Removal of the RF transmitter coil terminated the stimulation spikes. As illustrated in FIG. 10F, distinct ECG patterns were observed (inset), revealing the stimulation spike, followed by the narrow QRS for ventricular depolarization, and T wave for repolarization during a cardiac cycle. This cardiac stimulation was performed for >20 cycles to demonstrate electrical and contraction coupling. FIG. 10E further illustrates that the myocardial contraction in response to electrical stimulation was recorded as epicardial movements.

[0052] FIGs. 11 A-l IF illustrate an intravascular implantation of the pacemaker 100 to restore hemodynamic blood flow. In particular, FIGs. 11A-1 IF demonstrate that this electrical and mechanical coupling performs overdrive pacing and increases blood circulation to the hindlimbsof the anesthetized pig. FIGs. 1 1 A and 1 IB illustrate ECG and SpCh monitoring in response to cardiac contraction from 70 to 120 bpm. As illustrated in FIGs. 11 A and 1 IB, the RF transmitter coil was able to increase the rate of power transfer to the receiver coils, resulting in continuous wireless pacing from about 70 to 120 bpm, as evidenced by the ECG acquisition. In parallel, oxygen saturation of the peripheral artery (SpO2) during cardiac stimulation was monitored. FIG. 11C illustrates a placement of duplex ultrasound to detect blood flow from the femoral artery. FIG. 1 ID illustrates a pulsed wave Doppler that detected the pulsatile arterial blood flow in response to cardiac contraction. As illustrated in FIGs. 11C and 1 ID, an ultrasound probe (i.e., Doppler) was placed over the femoral artery, and pulsed wave Doppler detected the pulsatile blood flow during different states of a cardiac cycle. FIGs. 1 ID and 1 IF include markers tl to t4 to indicate the Doppler signals at different cardiac cycles, tl corresponds to diastole, t2 represents early systole, t3 represents mid-systole, and t4 represents end-systole, as indicated in FIGs. 1 ID and 1 IF. The color gradients as illustrated in FIG. 1 IF indicate the direction and magnitude of blood velocity toward the hindlimb. FIG. 1 IE illustrates the pulsed wave Doppler detected femoral arterial blood flow in response to cardiac pacing from about 70 to 120 bpm.

[0053] In one or more cases, the self-assembled implantable microtubular pacemaker (e.g., pacemaker 100) may be utilized for intravascular deployment and wireless pacing to restore cardiovascular function. The pacemaker 100 is implantable and operates battery -free having efficient power transfer and minimal power absorption over an anatomically wireless range. The pacemaker 100 may be used for intravascular deployment and implantation for the miniatured size to deliver up to DC of 5 V to overcome myocardial pacing threshold.

[0054] The design of the thin f-PCB film with a SEBS encapsulation provided a self-assembled rolling process to form the microtubular structure, thus allowing the deployment to the ACV (<3 mm). The magnetic field simulation guided an optimized circuit design to achieve a power transfer efficiency of 1.3% or about 1.3% at distances up to 3 cm. The stimulating electrodes (e.g., electrodes 208 and 210) of the microtubular pacemaker (e.g., pacemaker 100) are designed to contact with the endoluminal wall. The contact area of the electrodes is comparable to that of the distal electrode for a commercially designed leadless pacemaker. The in vivo demonstration on a pig model substantiates the functionality of the wireless intravascular pacing methodology via ACV implantation.

[0055] The frequency of 1 .0 MHz used for the inductive power transfer was to reduce radiation absorption by the bio-tissues and attenuation of power transfer due to the higher frequency band. The inductive power transferring at 1.0 MHz also meets the Federal Communication Commission specification (i.e., section 15.209) for the use of small antennas with low energy. The specific absorption rate (SAR) was simulated to be ~1.0 x 10-4 W / kg (temporal average), less than the FDA-specified safety level at 10 W / kg. The hemocompatibility of the microtubular pacemaker (e.g., pacemaker 100) has been demonstrated via anti coagulation to reduce the risk of acute thrombosis and immune responses.

[0056] In one or more cases, the self-assembled microtubular pacemaker (e.g., pacemaker 100) provides an entry point for intravascular deployment with translational implication for cardiac, gastric, neural, and urological stimulation. The self-assembled microtubular pacemaker (e.g., pacemaker 100) may jumpstart a non-beating heart and / or perform overdrive pacing from 70 bpm at resting to 120 bpm needed during physical activity. This implementation eliminates the need for a charge storage unit in the bioelectronics and obviates the need for open-chest thoracotomy, prolonged wound healing and other health care burdens.

[0057] Example chemical reagents for developing the pacemaker include, but are not limited to, PBS (e.g., 0.01 M; pH 7.4), xylene, and the like. The SEBS polymer layer may be, for example, SEBS (SEBS-H1221) elastomer. The formulation of the SEBS solution for spray coating may include 5 g of SEBS-H1221 elastomer mixed with 100 ml of xylene and stirred for 5 hours. The gold target for sputter coating may be 57 * 0.1 mm, 99.99%. The PCB layer may be a polyimide- based flexible PCB circuit membrane. The thickness of the PCB circuit membrane may be 80 pm or about 80 pm. Other materials used in the development and testing of the pacemaker include, for example, but are not limited to, fluorochrome-conjugated antibodies specific for CD45 (clone Hl 30), CD3 (clone OKT3), CD1 lb (clone ICRF44), CD 19 (clone HIB19), CD56 (clone HCD56), CD14 (clone HCD14), a human Fc receptor blocking solution (TrueStain FcX), and a fixable viability dye eFluor 506 (e506).

[0058] As described herein, the pacemaker 100 includes a plurality of electrical components. The electrical components for the flexible f-PCB membrane include, for example, capacitors, diodes, and voltage doubler complementary metal oxide semiconductor chips. The stimulation electrodes of the f-PCB were sputtered with a layer of gold with a thickness of 100 nm or about 100 nm, providing excellent electrochemical stability in electrolyte environment. A layer ofSEBS elastomer encapsulation was coated on the f-PCB membrane through a masked spraying method to further protect the integrated circuit (IC) from electrolyte environment and provide the adhesive property for the self-assembled rolling process. The thin f-PCB membrane was rolled into a microtube with a diameter of ~2.5 mm. The surface adhesiveness of the SEBS encapsulation contributed to the stability of the microtubular structure.

[0059] Compared to traditional circular and square transmitter coils, the hexagonal transmitter coil offers distinct advantages. For example, the hexagonal transmitter coil provides seamless splicing and flexible combinations, superior antimisalignment characteristics, and a higher level of cost-effectiveness. The transmitter coil (e.g., transmitter 202) was designed with the insulator- coated copper wires (AWG 26), resulting in a hexagonal configuration with a radius of 30 mm, an inductance of 38 pH, and a resistance of 2.6 ohms at 1.0 MHz. The transmitter coil may continuously operate for 5 hours or about 5 hours given a power consumption of 200 mW and 1000-mAh battery. The frequency of 1.0 MHz was used for inductive power transfer to reduce radiation absorption by the biotissues and attenuation of power transfer due to the higher frequency band. The copper wire of the transmitter coil was separated between the adjacent turns, spanning around 1.0 cm for six turns on a plane to reduce the parasitic capacitance and to increase the strength of magnetic field region in the normal direction to the transmitter coil. The skin depth (i.e., the depth where the current density is 1 / e ~ 37% of the value at the surface) of the copper coil wires was higher at a low frequency, thus reducing the AC resistance and increasing the corresponding quality factor (Q value). The inductive power transferring at 1.0 MHz also met the Federal Communication Commission specification (section 15.209) for the use of small antennas with low energy. The SAR was simulated to be ~1.0 x 10-4 W / kg (temporal average), far below the FDA-specified safety level at 10 W / kg.

[0060] The commercial software package ANSYS HFSS (ANSYS) was used to perform electromagnetic simulation to determine the optimal PTE. The 3D model for the transmitter coil in ANSYS used the copper wires that were configurated into a two-layer hexagon with a span of 1.0 cm for six turns. The transmitter coils with an outer diameter of 20, 24, 28, 30, and 32 mm are tuned to operate at a resonant frequency of 1 MHz. The distance between transmitter coil and the microtubular pacemaker was set at 2 and 3 cm, respectively. Considering that during the in vivo application scenarios, the dynamic beating heart can cause horizontal and angular misalignments that may influence the PTE. As such, these situations were further simulated. Thehorizontal misalignments of 0.0, 5.0, 7.5, and 10.0 mm were simulated at transverse and longitudinal direction, respectively. The angular misalignments were set 0°, 10°, 20°, and 30° as the axial rotating and tilting degree. The biological tissue parameters for SAR simulation include the dielectric constant (s), electrical conductivity (o), and density (p), with the values: s = 246, o = 0.53 S / m, and p = 1055 kg / m3. For continuous pacing, an external coil with 12 turns and an input power of 2 W was used and placed directly in front of the chest model.

[0061] The waveforms of the RF and stimulation DC pulse were performed with the digital storage oscilloscope. To characterize the wireless power transmission efficiency of the microtubular electronics, the voltages of the transmitter were set at 5, 8, 10, and 12 V with the distance varied from 0.5 to 3 cm. The electrochemical characterizations were conducted under a three-electrode configuration by using the Interface 1010E potentiostat. The electrochemical stability windows of the stimulation cathodes and anode were measured by linear sweep voltammetry at a scan rate of 5 mV / s in PBS solution. Electrochemical impedance spectroscopy was measured in the frequency range from 0.1 Hz to 1 MHz with a 5-mV amplitude at the opencircuit potential.

[0062] To evaluate the feasibility of the pacemaker for cardiac pacing, ex vivo experiments were conducted on male Yorkshire pigs (n = 4) weighing more than 50 kg and more than 14 weeks of age. All animal experiments were conducted in accordance with protocols approved by the University of California, Los Angeles (UCLA) IACUC. The pigs were anesthetized using intramuscular ketamine and midazolam, while fentanyl was administered intravenously for pain control during surgery. To maintain surgical plane of anesthesia throughout the procedure, 1 to 3% isoflurane was administered via endotracheal tube, and the animals were mechanically ventilated. A 6F introducer sheath was percutaneously inserted using the Seidinger technique into the right or left femoral artery to monitor blood pressure. Bupivacaine was subcutaneously injected into the chest, and a midline sternal incision was made to gain access to the thorax. Rib spreaders were used to expand the incision and expose the heart. The pericardium was incised to enable access to the heart.

[0063] The animal was humanely euthanized using a combination of pentobarbital and phenytoin, administered intravenously. Subsequently, the device was inserted by creating an incision in the ACV downstream of the implant location. The intravascular pacemaker was then introduced into the vessel via the opening. To achieve optimal positioning of the wireless powertransmitter, previous thoracic magnetic resonance imaging studies were referred to determine a mean distance of 20 mm between the intravascular pacemaker in the ACV and the subcutaneous transmitter in humans. On this basis, the wireless power transmitter was placed at a distance of 20 mm from the intravascular pacemaker. Immediately following euthanasia, pacing was initiated at a rate of 60 bpm to minimize cellular apoptosis and release of intracellular electrolytes. ECG readings were then observed and recorded to evaluate the pacing function. Video tracking of myocardial contraction was achieved by object tracking algorithms in OpenCV library.

[0064] All flow cytometry stains were performed in PBS for 15 min at 4°. Samples were stained with the fixable viability dye e506 mixed with human Fc receptor blocking solution (TrueStain FcX), followed by PBS washing to remove e506 and blocking antibodies. Antibody staining was added to all samples at specified dilutions according to the manufacturer’s instructions.

[0065] For biocompatibility testing in human PBMCs, healthy donor PBMCs were obtained from the UCLA CFAR Virology Core Laboratory, in accordance with federal and state regulations, without identification information. The biocompatibility of varied materials was assessed by culturing the healthy donor PBMCs in tissue culture treated nonpyrogenic polystyrene 24-well cell culture plates, using complete lymphocyte culture medium (CIO medium). RPMI 1640 supplemented with 10% (v / v) fetal bovine serum, 1% (v / v) Penicillin / Streptomycin / Glutamine, 1% (v / v) minimum essential medium nonessential amino acids, 10 mM Hepes, 1 mM sodium pyruvate, 50 mM 2-mercaptoethanol, and Normocin (100 mg / ml) was used to prepare CIO medium for all PBMC-related cultures. The PBMCs were cultured for 3 and 6 days in CIO medium, and their viability was then assessed. Viability was determined by staining the live cells with e506 viability dye. CD3+ cells were used to identify human T cells, CD 19+ cells were used to identify B cells, CD3-CD56+ cells were used to identify natural killer cells, CD14+CD1 lb+ cells were used to identify monocytes, and CD1 lb+CD14- cells were used to identify granulocytes.

[0066] Moreover, this application incorporates, by reference and in its entirety, the article: “A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy,” by Wang et al., Sci. Adv. 9, eadj0540 (2023), 18 October 2023.

[0067] The various embodiments described above are provided by way of illustration only and should not be construed to limit the claims attached hereto. Those skilled in the art will readilyrecognize various modifications and changes that may be made without following the example embodiments and applications illustrated and described herein, and without departing from the spirit and scope of the following claims.

Claims

CLAIMSWhat is claimed is:

1. An implantable device, comprising: a flexible printed circuit board (f-PCB) disposed between an adhesive first layer and an adhesive second layer, the f-PCB, the first layer, and the second layer being assembled in a tubular structure, wherein the f-PCB comprises a transmitter and a pair of electrodes operably coupled to one another via a circuit of the f-PCB, and wherein the transmitter is configured to control a wireless power transfer of energy to the electrodes.

2. The implantable device of claim 1, wherein the first layer and the second layer comprise a styrene-ethylene-butylene-styrene (SEBS) polymer.

3. The implantable device of claim 2, wherein the first layer and the second layer are applied to the f-PCB via a mask-spraying method, such that the f-PCB is encapsulated to prevent corrosion in an electrolyte-rich environment.

4. The implantable device of claim 1, wherein in an unassembled state, the implantable device comprises a planar shape.

5. The implantable device of claim 4, wherein the first layer is positioned on one side of the planar surface of the f-PCB, and wherein the second layer is positioned on a side of the planar surface of the f-PCB that is opposite the side of the first layer.

6. The implantable device of claim 1, wherein in an assembled state, the implantable device comprises a tubular shape, wherein one or both of the first layer and second layer adhere to one another to maintain the tubular structure of the implantable device.

7. The implantable device of claim 1, wherein the tubular structure of the implantable device facilitates intravascular implantation in an organ.

8. The implantable device of claim 1 , further comprising a guidewire, a portion of which is positioned within the tubular structure of the implantable device.

9. The implantable device of claim 1, wherein an end of the implantable device comprises a hoop configured to operably couple to a catheter when removing the implantable device from a body.

10. The implantable device of claim 1, wherein the pair of electrodes comprise an anode electrode and a cathode electrode configured to provide stimulation to an organ.

11. The implantable device of claim 1, wherein the pair of electrodes sputtered with a layer of gold on the f-PCB to provide electrochemical stability in an electrolyte-rich environment.

12. The implantable device of claim 1, wherein the circuit of the f-PCB is configured to receive alternating current (AC) waveforms from the transmitter and to convert and deliver the AC waveforms to rectified direct current (DC) pulses to the pair of electrodes.

13. The implantable device of claim 1 is configured for intravascular myocardial pacing.

14. The implantable device of claim 1, wherein the transmitter is configured to wirelessly receive power from another transmitter.

15. A tubular implantable device that facilitates intravascular implantation in an organ, comprising: a first adhesive polymer layer and a second adhesive polymer layer disposed on opposing sides of a flexible printed circuit board (f-PCB) and shaped into a tubular structure; and a guidewire, a portion of which is positioned within the tubular structure of the implantable device,wherein the f-PCB comprises a transmitter and a pair of electrodes operably coupled to one another via a circuit of the f-PCB, and wherein the transmitter is configured to control a wireless power transfer of energy to the electrodes.

16. The tubular implantable device of claim 15, wherein one or both of the first layer and second layer adhere to one another to maintain the tubular structure of the implantable device.

17. The tubular implantable device of claim 15, wherein an end of the implantable device comprises a hoop configured to operably couple to a catheter when removing the implantable device from a body.

18. The tubular implantable device of claim 15, wherein the pair of electrodes comprise an anode electrode and a cathode electrode configured to provide stimulation to the organ.

19. The tubular implantable device of claim 15, wherein the circuit of the f-PCB is configured to receive alternating current (AC) waveforms from the transmitter and to convert and deliver the AC waveforms to rectified direct current (DC) pulses to the pair of electrodes.

20. The tubular implantable device of claim 15 is configured for intravascular myocardial pacing.

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