Implantable pressure sensor

Abstract

An implantable pressure sensor. In some embodiments, a system includes a pressure sensor. The pressure sensor may include: an AT-cut quartz crystal configured to measure pressure, and a biocompatible coating, covering the AT-cut quartz crystal.

Description

274509WO M25-019L-WO1-aIMPLANTABLE PRESSURE SENSORCROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] The present application claims priority to and the benefit of U.S. Provisional Application No. 63 / 693,170, filed September 10, 2024, entitled "IMPLANTABLE PRESSURE SENSOR", the entire content of which is incorporated herein by reference.FIELD

[0002] One or more aspects of embodiments according to the present disclosure relate to pressure sensing, and more particularly to an implantable pressure sensor.BACKGROUND

[0003] Fluid pressure in fluid-filled cavities of a subject may fluctuate by various mechanisms and may be of clinical importance.

[0004] It is with respect to this general technical environment that aspects of the present disclosure are related.SUMMARY

[0005] According to an embodiment of the present disclosure, there is provided a system, including: a pressure sensor, the pressure sensor including: an AT-cut quartz crystal configured to measure pressure, and a biocompatible coating, covering the AT- cut quartz crystal.

[0006] In some embodiments, the pressure sensor is configured, when immersed in a fluid, to subject at least 60% of the surface of the AT-cut quartz crystal to the pressure of the fluid.

[0007] In some embodiments, the pressure sensor is configured, when in a fluid, to subject at least 80% of the surface of the AT-cut quartz crystal to the pressure of the fluid.

[0008] In some embodiments, the biocompatible coating is composed of polydimethylsiloxane.-1-4915-7137-0343, v. 1274509WO M25-019L-WO1-a

[0009] In some embodiments, the polydimethylsiloxane has a Young’s modulus greater than 5 kPa and less than 20 MPa.

[0010] In some embodiments, the system further includes a catheter, wherein the pressure sensor is secured to the catheter.

[0011] In some embodiments, the catheter is a ventricular shunt.

[0012] In some embodiments, the pressure sensor is secured to an end of the catheter.

[0013] In some embodiments, the pressure sensor has a mean implantation life, in a mammalian subject, of at least 60 days.

[0014] In some embodiments, the system further includes a readout circuit configured to measure a resonant frequency of the AT-cut quartz crystal and to infer a pressure from the measured resonant frequency.

[0015] According to an embodiment of the present disclosure, there is provided a system, including: a pressure sensor; the pressure sensor including: a piezoelectric resonator; and a biocompatible coating, covering the piezoelectric resonator, the pressure sensor being configured, when immersed in a fluid, to subject at least 60% of the surface of the piezoelectric resonator to the pressure of the fluid.

[0016] In some embodiments, the piezoelectric resonator is an AT-cut quartz crystal.

[0017] In some embodiments, the pressure sensor is configured, when in a fluid, to subject at least 80% of the surface of the AT-cut quartz crystal to the pressure of the fluid.

[0018] In some embodiments, the biocompatible coating is composed of polydimethylsiloxane.

[0019] In some embodiments, the polydimethylsiloxane has a Young’s modulus greater than 5 kPa and less than 20 MPa.

[0020] In some embodiments, the system further includes a catheter, wherein the pressure sensor is secured to the catheter.

[0021] In some embodiments, the catheter is a ventricular shunt.-2-4915-7137-0343, v. 1274509WO M25-019L-WO1-a

[0022] In some embodiments, the pressure sensor is secured to an end of the catheter.

[0023] In some embodiments, the pressure sensor has a mean implantation life, in a mammalian subject, of at least 60 days.

[0024] In some embodiments, the system further includes a readout circuit configured to measure a resonant frequency of the piezoelectric resonator and to infer a pressure from the measured resonant frequency.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] These and other features and advantages of the present disclosure will be appreciated and understood with reference to the specification, claims, and appended drawings wherein:

[0026] FIG. 1 is a block diagram of a system for measuring fluid pressure, according to an embodiment of the present disclosure;

[0027] FIG. 2A is a schematic cross-sectional view of an embodiment with a gas-filled cavity, according to an embodiment of the present disclosure;

[0028] FIG. 2B is a schematic cross-sectional view of an embodiment with a gas-filled cavity, according to an embodiment of the present disclosure;

[0029] FIG. 3 is a schematic cross-sectional view of a system for measuring the response of a quartz crystal to an applied force, according to an embodiment of the present disclosure;

[0030] FIG. 4A is a view of an end of a catheter and of a pressure sensor on the end of the catheter, according to an embodiment of the present disclosure;

[0031] FIG. 4B is a view of an end of a catheter and of a pressure sensor on the end of the catheter, according to an embodiment of the present disclosure;

[0032] FIG. 4C is a view of an end of a catheter and of a pressure sensor on the end of the catheter, according to an embodiment of the present disclosure.-3-4915-7137-0343, v. 1274509WO M25-019L-WO1-aDETAILED DESCRIPTION

[0033] The detailed description set forth below in connection with the appended drawings is intended as a description of exemplary embodiments of an implantable pressure sensor provided in accordance with the present disclosure and is not intended to represent the only forms in which the present disclosure may be constructed or utilized. The description sets forth the features of the present disclosure in connection with the illustrated embodiments. It is to be understood, however, that the same or equivalent functions and structures may be accomplished by different embodiments that are also intended to be encompassed within the scope of the disclosure. As denoted elsewhere herein, like element numbers are intended to indicate like elements or features.

[0034] Intracranial pressure (ICP) is pressure in the craniospinal region. Various factors affect ICP, including the physiological state of neural tissue, cerebral blood flow, and drainage of cerebral spinal fluid. The average intracranial pressure in a mammal may be within a range of ± 7-15 mmHg (with negative values indicating over-drainage using a shunt catheter placed in the ventricle), and any significant increase in pressure beyond 20 mmHg to 25 mmHg may accompany a variety of brain dysfunctions and injuries, such as stroke, hydrocephalus, or traumatic brain injury. Intracranial pressure monitoring may be useful to evaluate cerebral health for timely clinical intervention.

[0035] As such, some embodiments include a pressure sensor that may be implanted in a cerebral ventricle to measure the intracranial pressure. FIG. 1 shows a system for measuring fluid pressure in a fluid-filled cavity, such as a cerebral ventricle. A piezoelectric resonator, e.g., a quartz crystal 105, has attached to it two electrodes 110, to which are attached respective electrode wires 115. The assembly is covered in a biocompatible coating 120 and implanted in a fluid-filled cavity 125 of a subject, or “patient”. The subject may be any animal, e.g., a mammal, such as a human. Although a quartz crystal may be used as the piezoelectric resonator, the present disclosure is not limited to such embodiments and other types of piezoelectric resonators may be used instead of a quartz crystal.-4-4915-7137-0343, v. 1274509WO M25-019L-WO1-a

[0036] The quartz crystal 105 may be similar in shape and size to a quartz crystal microbalance (QCM). The quartz crystal 105 may be in the shape of a thin disc (with a thickness less than or equal to 10% of the diameter) and a diameter between 1 mm and 30 mm. The electrodes 110 may be composed of metal (e.g., gold), and formed by deposition of the metal on the circular surfaces of the disc.

[0037] In operation, the quartz crystal 105 may be subjected to the pressure of the fluid in the fluid-filled cavity 125, e.g., the pressure of the fluid in the fluid-filled cavity 125 may act on all or nearly all of the surface of the quartz crystal 105. This pressure may be transmitted (i) through the biocompatible coating 120 and, (ii) on portions of the quartz crystal 105 covered by the electrodes 110, through the electrodes 110. As such, when the pressure of the fluid in the fluid-filled cavity 125 changes, the volume of the quartz crystal 105 may change (e.g., it may be compressed, in response to an increase in the pressure of the fluid in the fluid-filled cavity 125), and, to the extent that the elasticity tensor of the quartz in the quartz crystal 105 is anisotropic, the shape of the quartz crystal 105 may also change.

[0038] In some embodiments, the strain in the quartz crystal 105 (e.g., the strain caused by the pressure of the fluid in the fluid-filled cavity 125) affects one or more of the resonant frequencies of the quartz crystal 105. As such, the pressure of the fluid in the fluid-filled cavity 125 may be measured (or monitored) by measuring (or monitoring) a resonant frequency of the quartz crystal 105 (e.g., the frequency of the series resonance of the quartz crystal 105 or the frequency of the parallel resonance of the quartz crystal 105) and converting the resonant frequency to a corresponding pressure using a suitable calibration function. The calibration function may be a polynomial, e.g., it may be a first order polynomial such that p = pO + k (f - fO), where pO and fO are a reference pressure (e.g., atmospheric pressure) and the corresponding resonant frequency respectively, f is the measured resonant frequency, k is the reciprocal of the rate of change of frequency with pressure, and p is the pressure calculated from the measured resonant frequency. The values of pO, fO, and k may be determined by a calibration procedure in which, for example, the assembly consisting of the quartz crystal-5-4915-7137-0343, v. 1274509WO M25-019L-WO1-a105, the electrodes 110, the electrode wires 115 and the biocompatible coating 120 is (i) immersed in a fluid initially at pressure pO, (ii) fO is measured, and (iii) the pressure of the fluid is then changed (e.g., increased) to a second value p1 and the corresponding resonant frequency f1 is measured. The value of k may then be calculated as (p1 - pO) I (f1 - fO). In some embodiments, a higher order polynomial (e.g., a quadratic of the form p = pO + k(f - fO) + k2 (f - fO)2is used as the calibration function. The calculation of the pressure from the resonant frequency may be performed by a processing circuit (discussed in further detail below).

[0039] Referring to FIGs. 2A and 2B, in some embodiments, instead of the entire surface of the quartz crystal 105 being subject to the pressure of the fluid in the fluid- filled cavity 125, a cavity 205 inside a sealed container 210 at a reference pressure (e.g., a cavity 205 filled with a gas (e.g., air or nitrogen), e.g., at atmospheric pressure) is adjacent to the quartz crystal 105, so that, for a disc-shaped quartz crystal 105 for example, one of the circular surfaces of the disc is subjected to the pressure of the fluid in the fluid-filled cavity 125 and the other circular surface is subjected to the pressure (e.g., atmospheric pressure) in the gas-filled cavity, and any pressure difference produces a bending force on the quartz crystal 105. For example, as shown in FIG. 2A, a gas-filled cylindrical cup 215 may be sealed to a disc-shaped quartz crystal 105, so that the cylindrical cup 215 and the quartz crystal 105 (which forms a lid for the cup 210) together form the sealed container 210.. When the pressure of the fluid in the fluid-filled cavity 125 is greater than the pressure of the gas in the sealed cylindrical cup, the quartz crystal 105 may bow inwards, into the cylindrical cup. Such a bending deformation may also (like a compressive deformation) cause a change in a resonant frequency of the quartz crystal 105 such that a measurement of the resonant frequency may be used to calculate the pressure of the fluid in the fluid-filled cavity 125.

[0040] In the embodiment of FIG. 2B, the sealed container 210 is fully sealed and the quartz crystal 105 need not perform a sealing function, but may instead be secured (e.g., bonded) to a surface of the sealed container 210. In such an embodiment at least the top surface of the sealed container 210 (in the orientation of FIG. 2B) may be sufficiently-6-4915-7137-0343, v. 1274509WO M25-019L-WO1-a compliant to allow the top surface, together with the quartz crystal 105, to bend when the pressure in the fluid-filled cavity 125 changes. For example, the top surface of the sealed container 210 may be at most a factor of 2 stiffer (for deformation in response to pressure changes) than the quartz crystal 105. In both of the embodiments illustrated in FIGs. 2A and 2B, the quartz crystal 105 and the sealed container 210 may be coated in a biocompatible coating 120. The biocompatible coating 120 may be sufficiently compliant to transmit substantially all of the pressure of the fluid-filled cavity 125 to the outward-facing surface of the quartz crystal 105.

[0041] The quartz crystal 105 may be an AT cut quartz crystal, and the mode of oscillation of the quartz crystal 105, at the resonant frequency used to measure the pressure, may involve bulk waves in the crystal (unlike some modes of oscillation in other types of quart crystals, which may involve surface waves). The deformation of the crystal when oscillating at the resonant frequency may be predominantly shear, with the upper surface of the quartz crystal 105 being displaced in a first direction parallel to the surface, and the lower surface of the quartz crystal 105 being displaced in a second direction parallel to the surface, the second direction being opposite to the first direction, as shown by the arrows in the right side of the rectangle, in FIG. 1 , corresponding to the quartz crystal 105.

[0042] A readout circuit 130 may be employed to measure the resonant frequency of the quartz crystal 105, for the purpose of measuring (e.g., calculating) the pressure of the fluid in the fluid-filled cavity 125. The readout circuit 130 may, for example, measure the impedance of the quartz crystal 105 as a function of frequency (and the resonant frequency may then be determined as the frequency at which the impedance has a local minimum (if the resonant frequency corresponds to a series resonance) or a local maximum (if the resonance corresponds to a parallel resonance)). In another embodiment, the quartz crystal 105 is connected to a feedback amplifier to form a circuit that has a closed-loop transfer function with a pole in the right half plane, the imaginary part of the pole being equal, or approximately equal, to the resonant frequency. This circuit may then oscillate at a frequency that is equal, or approximately equal, to the-7-4915-7137-0343, v. 1274509WO M25-019L-WO1-a resonant frequency, and the frequency of oscillation may be measured, e.g., using a frequency counter.

[0043] The pressure sensor may be made biocompatible by coating the quartz crystal 105 (and the electrodes 110 and a portion of each of the electrode wires 115) with a biocompatible material. As used herein, the assembly including the quartz crystal 105, the electrodes 110, the electrode wires 115, and the biocompatible coating 120 may be referred to as the “pressure sensor”. The biocompatible coating may be composed of polydimethylsiloxane (PDMS), for example. The PDMS may be produced using a process (e.g., using suitable proportions of PDMS part A and cross linker) that results in a relatively soft material. A soft material may more readily deform in response to contact with tissue of the subject, reducing friction with or pressure on the tissue and the inflammation or irritation of such tissue that may otherwise result. In some embodiments, the ratio of cross linker to PDMS part A is selected to be between 1 :30 and 1 :15 (e.g., 1 :20) so that the resulting cured biocompatible coating 120 is relatively soft, which, as mentioned above, may improve biocompatibility. The Young’s modulus of such a biocompatible coating 120 may be between 5 kPa and 20 MPa (e.g., 590 kPa). The pressure sensor may have a mean implantation life in a mammalian subject of at least 30 days, e.g., at least 60 days, or at least 90 days. As used herein, the mean implantation life is the mean length of the time interval, over a plurality of subjects, between (i) the time of implantation and (ii) the time of explantation because of an adverse biological reaction of the subject to the implant.

[0044] In some embodiments, the biocompatible coating 120 includes a plurality of carbon nanotubes (CNTs). For example, a mixture of between 3% and 12% (e.g., 8%) by weight of CNTs and PDMS part A (base) (e.g., 92% by weight PDMS part A) may be used to form the biocompatible coating 120. In such an embodiment, the pressure sensor may include a first layer of PDMS directly on the quartz crystal 105 and on the electrodes 110, and a second layer, of PDMS containing carbon nanotubes, on the first layer of PDMS; in such an embodiment the first layer of PDMS may form an insulating barrier-8-4915-7137-0343, v. 1274509WO M25-019L-WO1-a preventing the carbon nanotubes from forming a conductive path between the electrodes 110.

[0045] In some embodiments, the resonant frequency used to measure the pressure is between 1 MHz and 100 MHz, e.g., it may be 10 MHz. In some embodiments, the viscosity of the fluid surrounding the pressure sensor may affect the quality factor (or Q factor) of a resonant mode of the quartz crystal 105 (e.g., of the resonant mode the frequency of which is used to measure the pressure of the fluid). For example, a more viscous fluid may produce greater damping, and reduce the Q factor more, than a less viscous fluid would. As such, the viscosity of the fluid may be measured by measuring the Q factor of the resonant mode. An AT-cut crystal may be especially sensitive to viscosity because, as mentioned above, the deformation of the crystal at the resonant frequency may be predominantly shear (e.g., it may oscillate in a thickness shear mode); this may result in inducing shear in the fluid, which may cause power dissipation proportional to the viscosity of the fluid.

[0046] In some embodiments, as the Q factor changes (e.g., as a result of a change in the viscosity of the fluid) the resonant frequency may change also. For example, as the Q decreases, the resonant frequency may also decrease; in some embodiments the upper 3 dB point of the resonant transfer function (e.g., of the impedance of the quartz crystal 105) may remain substantially fixed, and the lower 3 dB point may be reduced. As such, the viscosity of the fluid may be measured by measuring the Q factor (e.g., of the impedance near the resonant frequency), or by measuring the resonant frequency, or by measuring the lower 3 dB point. In some embodiments, the pressure sensor may be placed in the brain parenchyma and used to measure the compliance or viscosity of the brain parenchyma. In some embodiments, the biocompatible coating 120 may be made sufficiently thin (e.g., less than 1 mm thick or less than 0.5 mm thick (or having a thickness between 0.01 mm and 3.00 mm) to reduce the extent to which the motion of the surfaces of the quartz crystal 105 is absorbed by (shear) deformation of the biocompatible coating 120 (because such absorption may reduce the extent to which-9-4915-7137-0343, v. 1274509WO M25-019L-WO1-a viscosity changes in the fluid affect the resonant frequency and Q factor of the quartz crystal 105).

[0047] In some embodiments, the quartz crystal 105 may be calibrated, e.g., the change in resonant frequency per unit change in pressure may be measured using a system such as that illustrated in FIG. 3. The quartz crystal 105 (which may have the shape of a circular disk) is supported at its edge by a rigid tube 305, and a vertical force F is applied at or near the center of the quartz crystal 105 by a rod 310. The applied force may be measured, for example, by mounting a load cell in the load path (e.g., the load cell may have a cylindrical tip and the rod 310 may be the cylindrical tip of the load cell). The force applied to the quartz crystal 105 may be adjusted by adding or removing weights exerting a downward force on the load cell, or by adjusting a screw mechanism which pushes down on the load cell. For example, the screw mechanism may push down on a spring which is compressed, increasing the downward force on the load cell, or the screw mechanism may press down directly on the load cell, which may deform slightly as the screw is tightened. The tip of the rod 310 may be coated with PDMS, e.g., to deflect unwanted vibrations (noise) from the quartz crystal 105 as the rod (e.g., the cylindrical tip of the load cell) makes contact with the quartz crystal 105. Forces ranging from about 10 mN to about 200 mN may be used to calibrate a quartz crystal 105 having an area of one square centimeter.

[0048] In some embodiments, the pressure sensor is integrated with a ventricular shunt. FIGs. 4A - 4C show three views of the superior end of a ventricular shunt 405 (e.g., a ventriculoperitoneal shunt) (the superior end being the end that, once the shunt is placed, is in the cerebral ventricle). The shunt 405 may include a silicone tube with an outer diameter between 1 mm and 10 mm (e.g., 2.5 mm as shown in FIGs. 4A - 4C). The pressure sensor (which may include the quartz crystal 105, and (not separately illustrated in FIGs. 4A - 4C) the electrodes 110, a portion of each of the electrode wires 115, and the biocompatible coating 120) may be secured to the end of the shunt 405 as shown. For example, the pressure sensor may be adhered to the end of the shunt 405 using PDMS as an adhesive; the PDMS adhesive may be applied between the pressure-10-4915-7137-0343, v. 1274509WO M25-019L-WO1-a sensor and the shunt 405 in liquid form (after the cross linker has been mixed with the PDMS part A, and before the PDMS has cured). The portion of the shunt 405 that is within the cerebral ventricle may have one or more perforations extending through the wall of the tube, so that the fluid pressure inside the shunt 405 and outside the shunt 405 may be the same (and so that both surfaces of the disc-shaped quartz crystal 105 are subjected to the fluid pressure of the cerebral ventricle). A portion of each of the electrode wires 115 may be within the tube, or one or both of the electrode wires may be outside of the tube. The electrode wires may exit from the subject through the (e.g., through a suitable port in the) skin of the subject, or the electrode wires 115 may be connected together through one or more loops of wire forming a secondary winding of a transformer, which may be just inside the skin of the subject (and the readout circuit 130 may be connected to one or more similar loops of wire on the outside of the skin of the subject, forming the primary winding of the transformer).

[0049] Embodiments disclosed herein provide various uses and benefits. For example, some embodiments provide information on the viscosity of the biological layer in the immediate vicinity of the sensor in addition to the fluid pressure of the compartment where it is placed. Some embodiments provide in-vivo monitoring of ICP (intracranial pressure). Some embodiments provide continuous real-time monitoring in a device that is more compact, and that has a simpler setup, than some invasive methods of ICP monitoring, enabling at-home use of the device. For instance, some embodiments may be realized in conjunction with implantable shunts for external ventricular drains (EVDs) for chronic monitoring of ICP in hydrocephalus patients. The sensor may be implanted at the site where pressure is to be monitored, and the readout may be placed on the scalp for on-body readouts.

[0050] As used herein, “a portion of’ something means “at least some of’ the thing, and as such may mean less than all of, or all of, the thing. As such, “a portion of’ a thing includes the entire thing as a special case, i.e., the entire thing is an example of a portion of the thing. As used herein, when a second quantity is “within Y” of a first quantity X, it means that the second quantity is at least X-Y and the second quantity is at most X+Y.-11 -4915-7137-0343, v. 1274509WO M25-019L-WO1-aAs used herein, when a second number is “within Y%” of a first number, it means that the second number is at least (1-Y / 100) times the first number and the second number is at most (1 +Y / 100) times the first number. As used herein, the word “or” is inclusive, so that, for example, “A or B” means any one of (i) A, (ii) B, and (iii) A and B.

[0051] Each of the terms “processing circuit” and “means for processing” is used herein to mean any combination of hardware, firmware, and software, employed to process data or digital signals. Processing circuit hardware may include, for example, application specific integrated circuits (ASICs), general purpose or special purpose central processing units (CPUs), digital signal processors (DSPs), graphics processing units (GPUs), and programmable logic devices such as field programmable gate arrays (FPGAs). In a processing circuit, as used herein, each function is performed either by hardware configured, i.e., hard-wired, to perform that function, or by more general- purpose hardware, such as a CPU, configured to execute instructions stored in a non- transitory storage medium. A processing circuit may be fabricated on a single printed circuit board (PCB) or distributed over several interconnected PCBs. A processing circuit may contain other processing circuits; for example, a processing circuit may include two processing circuits, an FPGA and a CPU, interconnected on a PCB.

[0052] As used herein, when a method (e.g., an adjustment) or a first quantity (e.g., a first variable) is referred to as being “based on” a second quantity (e.g., a second variable) it means that the second quantity is an input to the method or influences the first quantity, e.g., the second quantity may be an input (e.g., the only input, or one of several inputs) to a function that calculates the first quantity, or the first quantity may be equal to the second quantity, or the first quantity may be the same as (e.g., stored at the same location or locations in memory as) the second quantity.

[0053] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the inventive concept. As used herein, the terms “substantially,” “about,” and similar terms are used as terms of approximation and not as terms of degree, and are intended to account for the inherent-12-4915-7137-0343, v. 1274509WO M25-019L-WO1-a deviations in measured or calculated values that would be recognized by those of ordinary skill in the art.

[0054] As used herein, the term “major component” refers to a component that is present in a composition, polymer, or product in an amount greater than an amount of any other single component in the composition or product. In contrast, the term “primary component” refers to a component that makes up at least 50% by weight or more of the composition, polymer, or product. As used herein, the term “major portion”, when applied to a plurality of items, means at least half of the items. As used herein, any structure or layer that is described as being “made of” or “composed of” a substance should be understood (i) in some embodiments, to contain that substance as the primary component or (ii) in some embodiments, to contain that substance as the major component.

[0055] It will be understood that when an element or layer is referred to as being “on”, “connected to”, “coupled to”, or “adjacent to” another element or layer, it may be directly on, connected to, coupled to, or adjacent to the other element or layer, or one or more intervening elements or layers may be present. In contrast, when an element or layer is referred to as being “directly on”, “directly connected to”, “directly coupled to”, or “immediately adjacent to” another element or layer, there are no intervening elements or layers present.

[0056] Any numerical range recited herein is intended to include all sub-ranges of the same numerical precision subsumed within the recited range. For example, a range of "1.0 to 10.0" or “between 1.0 and 10.0” is intended to include all subranges between (and including) the recited minimum value of 1.0 and the recited maximum value of 10.0, that is, having a minimum value equal to or greater than 1 .0 and a maximum value equal to or less than 10.0, such as, for example, 2.4 to 7.6. Similarly, a range described as “within 35% of 10” is intended to include all subranges between (and including) the recited minimum value of 6.5 (i.e., (1 - 35 / 100) times 10) and the recited maximum value of 13.5 (i.e., (1 + 35 / 100) times 10), that is, having a minimum value equal to or greater than 6.5 and a maximum value equal to or less than 13.5, such as, for example, 7.4 to-13-4915-7137-0343, v. 1274509WO M25-019L-WO1-a10.6. Any maximum numerical limitation recited herein is intended to include all lower numerical limitations subsumed therein and any minimum numerical limitation recited in this specification is intended to include all higher numerical limitations subsumed therein.

[0057] It will be understood that when an element is referred to as being “directly connected” or “directly coupled” to another element, there are no intervening elements present. As used herein, “generally connected” means connected by an electrical path that may contain arbitrary intervening elements, including intervening elements the presence of which qualitatively changes the behavior of the circuit. As used herein, “connected” means (i) “directly connected” or (ii) connected with intervening elements, the intervening elements being ones (e.g., low-value resistors or inductors, or short sections of transmission line) that do not qualitatively affect the behavior of the circuit.

[0058] Some embodiments may include features of the following numbered clauses:1. A system, comprising: a pressure sensor, the pressure sensor comprising: an AT-cut quartz crystal configured to measure pressure, and a biocompatible coating, covering the AT-cut quartz crystal.2. The system of clause 1 , wherein the pressure sensor is configured, when immersed in a fluid, to subject at least 60% of the surface of the AT-cut quartz crystal to the pressure of the fluid.3. The system of clause 1 or clause 2, wherein the pressure sensor is configured, when in a fluid, to subject at least 80% of the surface of the AT-cut quartz crystal to the pressure of the fluid.4. The system of any one of the preceding clauses, wherein the biocompatible coating is composed of polydimethylsiloxane.-14-4915-7137-0343, v. 1274509WO M25-019L-WO1-a5. The system of clause 4, wherein the polydimethylsiloxane has a Young’s modulus greater than 5 kPa and less than 20 MPa.6. The system of any one of the preceding clauses, further comprising a catheter, wherein the pressure sensor is secured to the catheter.7. The system of clause 6, wherein the catheter is a ventricular shunt.8. The system of clause 6 or clause 7, wherein the pressure sensor is secured to an end of the catheter.9. The system of any one of the preceding clauses, wherein the pressure sensor has a mean implantation life, in a mammalian subject, of at least 60 days.10. The system of any one of the preceding clauses, further comprising a readout circuit configured to measure a resonant frequency of the AT-cut quartz crystal and to infer a pressure from the measured resonant frequency.11. A system, comprising: a pressure sensor; the pressure sensor comprising: a piezoelectric resonator; and a biocompatible coating, covering the piezoelectric resonator, the pressure sensor being configured, when immersed in a fluid, to subject at least 60% of the surface of the piezoelectric resonator to the pressure of the fluid.12. The system of clause 11 , wherein the piezoelectric resonator is an AT-cut quartz crystal.-15-4915-7137-0343, v. 1274509WO M25-019L-WO1-a13. The system of clause 11 or clause 12, wherein the pressure sensor is configured, when in a fluid, to subject at least 80% of the surface of the AT-cut quartz crystal to the pressure of the fluid.14. The system of any one of clauses 11 to 13, wherein the biocompatible coating is composed of polydimethylsiloxane.15. The system of clause 14, wherein the polydimethylsiloxane has a Young’s modulus greater than 5 kPa and less than 20 MPa.16. The system of any one of clauses 11 to 15, further comprising a catheter, wherein the pressure sensor is secured to the catheter.17. The system of clause 16, wherein the catheter is a ventricular shunt.18. The system of clause 16 or clause 17, wherein the pressure sensor is secured to an end of the catheter.19. The system of any one of clauses 11 to 18, wherein the pressure sensor has a mean implantation life, in a mammalian subject, of at least 60 days.20. The system of any one of clauses 11 to 19, further comprising a readout circuit configured to measure a resonant frequency of the piezoelectric resonator and to infer a pressure from the measured resonant frequency.

[0059] Although exemplary embodiments of an implantable pressure sensor have been specifically described and illustrated herein, many modifications and variations will be apparent to those skilled in the art. Accordingly, it is to be understood that an implantable pressure sensor constructed according to principles of this disclosure may-16-4915-7137-0343, v. 1274509WO M25-019L-WO1-a be embodied other than as specifically described herein. The invention is also defined in the following claims, and equivalents thereof.4915-7137-0343, v. 1

Claims

274509WO M25-019L-WO1-aWHAT IS CLAIMED IS:

1. A system, comprising: a pressure sensor, the pressure sensor comprising: an AT-cut quartz crystal configured to measure pressure, and a biocompatible coating, covering the AT-cut quartz crystal.

2. The system of claim 1 , wherein the pressure sensor is configured, when immersed in a fluid, to subject at least 60% of the surface of the AT-cut quartz crystal to the pressure of the fluid.

3. The system of claim 1 , wherein the pressure sensor is configured, when in a fluid, to subject at least 80% of the surface of the AT-cut quartz crystal to the pressure of the fluid.

4. The system of claim 1 , wherein the biocompatible coating is composed of polydimethylsiloxane.

5. The system of claim 4, wherein the polydimethylsiloxane has a Young’s modulus greater than 5 kPa and less than 20 MPa.

6. The system of claim 1 , further comprising a catheter, wherein the pressure sensor is secured to the catheter.

7. The system of claim 6, wherein the catheter is a ventricular shunt.

8. The system of claim 6, wherein the pressure sensor is secured to an end of the catheter.-18-4915-7137-0343, v. 1274509WO M25-019L-WO1-a9. The system of claim 1 , wherein the pressure sensor has a mean implantation life, in a mammalian subject, of at least 60 days.

10. The system of claim 1 , further comprising a readout circuit configured to measure a resonant frequency of the AT-cut quartz crystal and to infer a pressure from the measured resonant frequency.

11. A system, comprising: a pressure sensor; the pressure sensor comprising: a piezoelectric resonator; and a biocompatible coating, covering the piezoelectric resonator, the pressure sensor being configured, when immersed in a fluid, to subject at least 60% of the surface of the piezoelectric resonator to the pressure of the fluid.

12. The system of claim 11 , wherein the piezoelectric resonator is an AT-cut quartz crystal.

13. The system of claim 12, wherein the pressure sensor is configured, when in a fluid, to subject at least 80% of the surface of the AT-cut quartz crystal to the pressure of the fluid.

14. The system of claim 11 , wherein the biocompatible coating is composed of polydimethylsiloxane.

15. The system of claim 14, wherein the polydimethylsiloxane has a Young’s modulus greater than 5 kPa and less than 20 MPa.-19-4915-7137-0343, v. 1274509WO M25-019L-WO1-a16. The system of claim 11 , further comprising a catheter, wherein the pressure sensor is secured to the catheter.

17. The system of claim 16, wherein the catheter is a ventricular shunt.

18. The system of claim 16, wherein the pressure sensor is secured to an end of the catheter.

19. The system of claim 11 , wherein the pressure sensor has a mean implantation life, in a mammalian subject, of at least 60 days.

20. The system of claim 11 , further comprising a readout circuit configured to measure a resonant frequency of the piezoelectric resonator and to infer a pressure from the measured resonant frequency.4915-7137-0343, v. 1

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