DEVICES AND METHODS FOR PARAMETER MEASUREMENT

Abstract

A thin-film, diaphragm based device is disclosed which can be used to perform an array of sensing and actuating operations where a very thin profile is desired, such as in millimeter, micrometer, or nanometer tight spaces.

Claims

1. A device comprising: a substrate; a diaphragm coupled to the substrate, wherein the diaphragm is a thin film capacitive transducer between 10 m and 20 m thick; and a chamber structure between the diaphragm and the substrate, wherein: the diaphragm is coupled to the substrate via an adhesive; the chamber structure comprises a bonding pad around the perimeter of the chamber structure; the chamber structure is positioned between the diaphragm and the adhesive; and the substrate is approximately 50 m thick and is electrically conductive.

2.-6. (canceled)

7. The device of claim 1 wherein the substrate and diaphragm are configured as a wireless resonant pressure sensor sized for implantation in a human artery.

8. The device of claim 1 wherein the diaphragm is approximately 15 m thick.

9. (canceled)

10. The device of claim 1 wherein the substrate is configured as an antenna.

11. The device of claim 1 wherein the device is configured to measure pressure with a linear sensitivity of approximately four percent between 0 and 400 mm Hg.

12. The device of claim 1 wherein the substrate and the diaphragm are biocompatible.

13. The device of claim 1 wherein the device is configured as a pressure sensor.

14. The device of claim 1 wherein the device is configured as an audio wave sensor.

15. The device of claim 1 wherein the device is configured as a chemical sensor.

16. The device of claim 1 wherein the device is configured as a biological sensor.

17. The device of claim 1 wherein the device is configured as an optical sensor.

18. The device of claim 1 wherein the device is configured as a pump.

19. The device of claim 1 wherein the device is configured as a valve.

20. The device of claim 1 further comprising a first electrode coupled to the diaphragm and a second electrode coupled to the substrate.

21. A method of fabricating a thin film capacitive transducer, the method comprising; providing a substrate; providing a diaphragm, wherein the diaphragm is between 10 m and 20 m thick; and coupling the diaphragm to the substrate via an adhesive to provide a chamber structure between the diaphragm and the substrate, wherein: the chamber structure comprises a bonding pad around the perimeter of the chamber structure; the chamber structure is positioned between the diaphragm and the adhesive; and the substrate is approximately 50 m thick and is electrically conductive.

22. (canceled)

23. The method of claim 21 further comprising inserting the chamber structure between the diaphragm and the substrate before coupling the diaphragm to the substrate.

24. The method of claim 23 wherein the diaphragm and chamber structure are constructed using photolithography.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0078] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present disclosure. The invention may be better understood by reference to one of these drawings in combination with the detailed description of specific embodiments presented herein.

[0079] FIG. 1 shows an exploded view of one embodiment of a device according to the present disclosure.

[0080] FIG. 2 shows a section view of the embodiment of FIG. 1.

[0081] FIG. 3 shows a graph of capacitance versus pressure for one embodiment of a device according to the present disclosure.

[0082] FIGS. 4-9 illustrate properties of the embodiment of FIG. 3 as measured over period of several days.

[0083] FIGS. 10-11 illustrate measurements of the embodiment of FIG. 3 of dynamic signals from inside a flow loop with pulsatile pressure.

[0084] FIG. 12 shows a schematic of one embodiment of a device configured as an audio sensor.

[0085] FIG. 13 shows data recorded with the embodiment of FIG. 16.

[0086] FIGS. 14-25 show circuits and data for a specific embodiment for insole pressure measurement.

[0087] FIGS. 26-28 illustrate data for exemplary embodiments of four sensors according to the present disclosure over one month in saline under pulsatile pressure.

[0088] FIGS. 29-32 contain regressions and drift of parameters over the one month period for the data illustrated in FIGS. 26-28.

[0089] FIGS. 33-39 contain data from one sensor which addresses the source of drift in the parameters for the data illustrated in FIGS. 29-32.

[0090] FIG. 40 illustrates a schematic of an exemplary embodiment of a resonator according to the present disclosure.

[0091] FIG. 41 illustrates resonance frequency signals at different pressures for exemplary embodiments of devices according to the present disclosure.

[0092] FIGS. 42-43 illustrate data showing the pressure dependence of diaphragm resonance frequency.

[0093] FIGS. 44-45 illustrate schematics of exemplary embodiments of resonator devices anchored to a structure according to the present disclosure.

[0094] FIG. 46 illustrates a schematic of acoustic interrogation of an exemplary embodiment of a mechanical resonator according to the present disclosure.

[0095] FIG. 47 illustrates schematics for wireless sensing modalities for exemplary embodiments of implantable sensors according to the present disclosure.

[0096] FIG. 48 illustrates a coordinate system and a schematic of an exemplary embodiment of an analytical model according to the present disclosure.

[0097] FIGS. 49-51 illustrate an experimental setup used to obtain results previously shown in FIGS. 41-43.

[0098] FIGS. 52-53 illustrate frequency versus pressure data in the audible range obtained from exemplary embodiments of resonators according to the present disclosure.

[0099] FIGS. 54-55 illustrate data showing the penetration of audible acoustic waves in soft tissue.

[0100] FIG. 56 illustrates the level of acoustic energy that can be delivered to a resonator for different materials according to the present disclosure.

[0101] FIG. 57 illustrates the reflected pressure ratio and reflected power ratio for soft tissue in combination for different materials.

[0102] FIGS. 58-60 illustrate a schematic of an experimental set up for ultrasonic measurements and data obtained from the experiment.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0103] Referring initially to FIGS. 1-2, an exemplary embodiment of a device 100 configured as a thin film sensor comprises a diaphragm 110, a chamber structure 120, an adhesive 130 and a substrate 140. In the embodiment shown, diaphragm 110 is configured as a thin film diaphragm transducer between 10 m and 20 m thick and is bonded to substrate 140 via adhesive 130. In particular embodiments, diaphragm 110 is approximately 15 m thick and substrate 140 is approximately 50 m thick. In the present disclosure, the thickness of a material is measured across the primary plane of the material (i.e. the minimum dimension for a given layer of material, as would be measured in a vertical direction in the configuration shown in FIG. 2).

[0104] In the illustrated embodiment, chamber structure 120 comprises a bonding pad 125 around its perimeter and chamber structure 120 is positioned between diaphragm 110 and substrate 140. In exemplary embodiments of device 100, substrate 140 can be electrically conductive, and in certain embodiments can be configured as an antenna.

[0105] Exemplary embodiments of device 100 may be fabricated by constructing a thin sensing film, which comprises of an array of diaphragms 110 enclosed by bonding pads 125. In certain embodiments, to construct the sensing film, multiple layers of photolithography with various polyimides can be performed on a carrier substrate. The diaphragm can be defined in one step, the chamber walls can be defined in a second step, and a thin adhesive film applied in a third step. The sensing film can then be released from the carrier.

[0106] In exemplary fabrication techniques, the sensing film can then be bonded to the substrate of choice. In certain embodiments, the thin adhesive can be deposited onto a conductive substrate. If the substrate is not inherently conductive, a thin conductive film may be deposited to provide a bottom electrode of the diaphragm sensor. The sensing film can then be bonded to the substrate under pressure and temperature.

[0107] In certain embodiments, the final fabrication step is to sputter an electrode and bond lead wires. For example, a thin conductive film can be deposited on top of the sensing film to define the top electrode of the diaphragm sensor. Lead wires can then be bonded onto the top and bottom electrodes.

[0108] In certain embodiments of the sensor, the sensing film (e.g. diaphragm 110) is 10-15 m thick and substrate 140 is 50 m thick stainless steel. In certain embodiments, diaphragms 110 form a sensing film that is 3 mm10 mm, but it can be of arbitrary size to suit the application.

[0109] In certain embodiments, substrate 140 may be formed by polymers processing techniques. Other microfabrication techniques could produce a similarly-structured device composed of other materials, including traditional microfabrication ceramics such as silicon, silica, quartz, silicon nitrides, other nitrides, other oxides, and other insulating or semiconducting materials.

[0110] During operation of device 100, deflection of diaphragm 110 toward and away from substrate 140 can be measured by changes in electrical properties and correlated to environmental conditions or parameters affecting device 100. For example, in certain embodiments, the capacitance of device 100 (measured between diaphragm 110 and substrate 140) can be correlated to pressure. Referring now to FIG. 3, one example illustrates a substantially linear relationship between the measured capacitance (in pF) versus the pressure on diaphragm 110 (measured in mmHg). FIGS. 4-9 illustrate other properties of the embodiment of FIG. 3 as measured over period of several days. FIGS. 10 and 11 illustrate measurements of the embodiment of FIG. 3 of dynamic signals from inside a flow loop with pulsatile pressure. FIG. 10 illustrates waveforms from device 100 and a reference sensor. As illustrated, the average difference is approximately 1 mm Hg.

[0111] Referring now to FIGS. 12 and 13, a schematic of device 100 (and resulting data) are shown for an embodiment configured as an audio sensor. In this embodiment, device 100 senses an audio wave 150, which causes deflection of diaphragm 110 (not labeled in FIG. 6 for purposes of clarity; see FIGS. 1 and 2 for view depicting diaphragm 110). Diaphragm 110 deflections cause a change in the measured capacitance/voltage across device 100, which can be viewed as a waveform on display 160.

[0112] In the graph shown in FIG. 13, audio frequencies were recorded with high fidelity up to 10 kHz, indicating certain embodiments of device 100 may be suitable for use for hearing aid implants. In addition, the ability to record frequencies up to 10 kHz also indicate the potential utility of device 100 in cardiovascular applications due to the ability to faithfully record high frequency information in the pressure waveform.

[0113] Device 100 can be used in many different applications. For example, device 100 can be configured for use as a sensor, including a pressure, acoustic, force or flow sensor. Device 100 may also be configured as a mechanical actuating device, including for example an electrostatically (or pneumatically)-driven membrane that can be used as a pump or valve in microfluidics applications. For example, in a valve configuration, diaphragm 110 can be deflected outward (e.g. away from substrate 140) to occlude flow and toward substrate 140 to allow flow to pass over diaphragm 110.

[0114] In still other embodiments, device 100 can be configured a capacitive microphone, including for example configuration a hearing aid.

[0115] In certain embodiments, device 100 can be configured as a chemical or biological sensor. For example, chamber structure 120 can be configured as a polymer or hydrogel with selective absorption that can swell and deflect diaphragm 110 in the presence of certain analytes.

[0116] In particular embodiments, device 100 may also be used for detecting chemical or biological analytes by mass loading of the sensing diaphragm, which changes its resonance frequency. The sensing diaphragm can have analyte receptors bound to its surface and the resonance frequency of the sensing diaphragm can be monitored by actuating device 100 electrostatically or thermally. Detection of the analyte occurs by recording the shift in resonant frequency of the diaphragm.

[0117] In specific embodiments, device 100 may be configured for indirect sensing by principles similar to those used in a Golay cell. For example, chamber structure 120 may be filled with a gas that expands with increased temperature and causes deflection of diaphragm 110. In particular embodiments, diaphragm 110 may be coated with a bandpass filter to provide for specific detection of light wavelengths or color. Such configurations could be used in imaging or retinal implant applications.

[0118] In certain embodiments, device 100 can be configured as a thin-film pressure sensor in an inductor-capacitor (LC) resonator for a wireless implantable blood pressure sensor. In particular embodiments, device 100 can operate by capacitive, resistive, and resonant mechanisms. In exemplary embodiments, device 100 can sense a broad range of factors, individually and multiple simultaneously. Device 100 can be configured as an electrical inductor-capacitor (LC) resonator that measures pressure by a thin film capacitive transducer that resonates with a stent-like antenna.

[0119] In exemplary embodiments, the thin active region of the sensor is decoupled from a thick inactive substrate. Certain embodiments can incorporate the use of a shape-memory NiTi as an antenna for percutaneous catheter delivery of the device. In certain embodiments, movements in local pressure change the transducer capacitance and thus shift the resonance frequency. In particular embodiments, the resonance frequency can be monitored externally by magnetic coupling to determine intravascular pressure.

[0120] In specific embodiments, the sensor can be bonded to a thin metallic substrate and coupled to a flexible NiTi stent-antenna (inductor), and the diaphragm sensor and inductive antenna form an electrical inductor-capacitor (LC) resonator.

[0121] In certain exemplary embodiments, device 100 has a thin profile, is wireless, biocompatible, implantable, and allows for intravascular implantation for blood pressure sensing. In particular embodiments, device 100 can be fabricated with biocompatible materials, is flexible and due to thin profile allows for 3-D conformations of sensor in vivo, allows for implementation in medium to small arteries, including the peripheral arteries.

[0122] In particular embodiments, device 100 can be bonded to virtually any substrate, and be integrated or embedded into various devices. The thin and flexible profile of device 100 is suitable for implantation into constrained spaces which were previously inaccessible for sensors.

[0123] The replacement of a thick silicon wafer onto which most pressure sensors are built with a very thin substrate (or the surface of an existing device or implant, including e.g. a stent) can save hundreds of micrometers of thickness which can be critical in particular applications. For example, one embodiment enables the development of a wireless resonant pressure sensor which is suitable for implantation in a large, medium, or small sized artery. As described in the literature reviews on endovascular blood pressure sensing devices and on pressure transducers, transducer size has been a limiting factor in the development of small implantable devices.

[0124] As described previously, exemplary embodiments of the present disclosure substitute the platform for the sensing diaphragm to reduce sensor thickness. Commercially available pressure sensors use silicon wafer as substrates with a thickness of about 500 m, most of which can be eliminated by integrating the sensing element onto a robust surface of the device.

Test Data

[0125] FIGS. 26-28 provide raw data on four sensors over one month in saline under pulsatile pressure. The data includes all tracked parameters, and the sensors had an initial two week immersion period in saline to allow parameter values to settle. Those values were then measured two times per week.

[0126] FIGS. 29-32 contain regressions and drift of parameters over the one month period. A graph at the end shows average drift in each parameter.

[0127] FIGS. 33-39 contain data from one sensor which addresses the source of drift in the parameters. Pressure was increased to 400 mmHg and pressure sensitivity curves were recorded; this was repeated for ten consecutive cycles. Some drift in sensor parameters are noted (for instance, 0.15% increase in baseline capacitance). The sensor was left alone for a twelve hour break, and then ten more cycles were performed. For almost all of the parameters, after the twelve hour break, the parameter value returned to the original value from day one, indicating that the drift in parameters was not permanent (e.g., a hysteresis effect which can be addressed during development and commercial design).

[0128] Design and fabrication of exemplary embodiments requires detailed knowledge and synthesis of multiple fields including microelectronics, microfabrication, cardiovascular medicine, and biomaterials. Additionally, silicon wafers are the epicenter of the microelectronics and microfabrication fields; departing from this fabrication orthodoxy is difficult.

[0129] Embodiments of the current invention include a class of resonant sensors which can be used in a shoe insole for monitoring foot pressures. The general sensor is a resistor-inductor-capacitor (RLC) resonant circuit, which allows for either capacitive sensing or resistive sensing. FIG. 14 shows circuit schematics of these two possible configurations. In both cases, an external device with a small coil and a radio link (e.g., Bluetooth), such as a clip on the outer shoe, an anklet, or a waist belt, can interrogate the sensor and transmit the pressure signals to a smart device, computer, or wireless network.

[0130] In the capacitive design, a planar conductive coil is electrically connected to a capacitive pressure transducer to form an RLC tank, which is then embedded into an insole. The resonance frequency of the tank depends on the applied pressure. The sensor can be interrogated by an external coil which sweeps across a specified frequency range to monitor shifts in the resonance frequency.

[0131] In the resistive design, a planar conductive coil is electrically connected to a capacitor and a resistive transducer to form an RLC tank, which is then embedded into an insole. In this case, the resonance frequency of the tank is fixed, but the quality of resonance (quality factor Q) depends on the applied pressure. The sensor can be interrogated by an external coil at a fixed frequency by monitoring the strength of the magnetically coupled signal.

[0132] The capacitive design of an RLC sensor has been enabled. Referring back now to FIG. 15, a prototype insole is shown with a thin film capacitive transducer and an embedded 2-turn coil. The prototype has a strong and linear pressure sensitivity (40 kHz/PSI; R2=0.993). Further experimental data are attached in an appendix. A video of the sensor in operation will be sent electronically. The particular type of capacitive transducer is non-essential to the invention. A variety of thin transducers could easily be used, from capacitive microsensors to custom capacitive sensors made from a sandwich of thin metal foil with a compressible dielectric in the middle.

[0133] FIGS. 17-19 provide pressure data for various embodiments, while FIG. 20 provides a schematic showing different features of existing systems and an embodiment of the present disclosure using a magnetic coupling and a radio link.

[0134] FIGS. 21-25 provide data on a wireless insole reading range according to exemplary embodiments of the present disclosure. For all sensors, data was acquired with a non-optimized sensor and a non-optimized interrogation system. The impedance analyzer operated at 0.5V across the interrogating coil (instrument limit). Industry RFID interrogators frequently use >10V to increase sensitivity, and frequently have interrogation distances of >1 m for resonant tags approximately 1 cm.

[0135] It is understood that the above-described devices and methods are merely non-limiting examples of embodiments of the devices and methods disclosed herein.

[0136] Exemplary embodiments of the present disclosure include resonators that operate in the audible acoustic range. Existing systems typically stipulate stimulation in the ultrasound range.

[0137] Bandwidth of the acoustic transmitter and/or receiver in exemplary embodiments of the present disclosure is much lower than standard ultrasound crystals. In certain embodiments, a unique probe may be developed for this application in the 1-20 kHz range.

[0138] Mechanical resonators are most sensitive to gauge pressure, and only to the first several hundred mmHg, after which sensitivity drops considerably. Therefore, it is not possible simply to use or test any commercially available pressure sensor with a micromachined diaphragm, which have chambers underneath which are frequently hermetically sealed under vacuum. In the case of vacuum sealed, commercially available pressure sensors, the gauge pressure across the diaphragm at the physiological range is >800 mmHg, which offers negligible pressure sensitivity if used as a mechanical resonator.

[0139] An exemplary embodiment of a prototype resonator is square polyimide diaphragm (500 um long, 5 um thick) over a closed air chamber, as shown in FIG. 40. In this embodiment, a square diaphragm made of polyimide over an air chamber is bonded to stainless steel substrate.

[0140] Modification of the standard equation for determining the resonance frequency of such a diaphragm (Roark) yields the following expression for resonance frequency with a strong pressure dependence

[00001]$F\left(p\right)=\frac{36}{2.Math.}.Math.\sqrt{\frac{\mathrm{Dg}}{a^4.Math.\left(w+p\right)}}$

where

[00002]$D=\frac{{\mathrm{Et}}^3}{12.Math.\left(1-v^2\right)}$

is the flexural rigidity of the diaphragm, v is the poisson ratio of the diaphragm material, E is the elastic modulus of the diaphragm material, t is the diaphragm thickness, a is the square diaphragm length, g is the gravitational constant, w is the weight of the diaphragm per unit area, and p is externally applied pressure (gauge pressure across the diaphragm).

[0141] Experimental testing shows good agreement with the theory. An impulse test was applied to the prototype diaphragms at various pressures to induce resonance. FIG. 41 clearly shows the strong pressure dependence of the resonance on local pressure. FIGS. 42 and 43 show that the experimental data matches the theory well. Response of the mechanical resonator to an impulse response is shown at different pressures. Increasing pressure reduces the resonance frequency. There is a good match between experimental vs predicted resonance frequency at various pressures, for a square polyimide diaphragm 500 um long and Sum thick.

[0142] Further theoretical analysis shows that ceramic resonators should given even better pressure responses, due to their rigidity. Additionally, the outstanding mechanical stability of ceramics, particularly monocrystalline ceramics of silicon and SiO.sub.2 (quartz), should lend excellent robustness and long term sensing stability.

[0143] FIGS. 44 and 45 illustrate variations of a conceived ceramic resonator, anchored to a stent or stent-like structure. In FIG. 44, the resonator is bonded to the stent surface, while in FIG. 45 the resonator is embedded into the stent.

[0144] Once percutaneously implanted, the resonator can be interrogated wirelessly by an acoustic impulse test. FIG. 46 illustrates how a piezo device at the skin surface can send a pulse to the resonator, induce vibration, and read the frequency of the vibration. In section 1 of FIG. 46, the piezo sends an impulse, either a square wave or a sine wave near the resonance frequency of the resonator. In section 2, the impulse stimulates vibration of the resonator, which produces a pressure wave with an oscillating decay at its resonance frequency. The piezo switches to listen mode, or a second receiving piezo is used, to record the resonator pressure wave.

[0145] If the resonance frequency of the resonator is sufficiently high (>1 kHz), >>100 samples of blood pressure samples can be taken during the pressure wave cycle. This should allow for a dense recreation of the blood pressure waveform.

[0146] In the past several decades, many wireless sensing platforms have been developed which utilize a radio link to transmit the sensed data. Currently, with small Bluetooth-like radio links and smart devices, these platforms are still in full force. There is a miniaturization limit, however, due the numerous components such as power sources, circuitry, and antennas. Resonance based systems offer an alternative for wireless sensing, because resonators are typically very simple structures, can be made small, and efficiently receive and transmit energy within a certain frequency range. FIG. 47 compares these wireless sensing modalities for implantable sensors, and optical methods could also be included in this comparison. In wireless modalities for implantable sensors, conventional wireless systems are bulky, with many components. Resonant systems have fewer components, no power requirements, and can be interrogated magnetically or acoustically

[0147] While well known in the physics, mechanics, and electrical literatures for over a century, resonance based sensing systems have become more intensively investigated since the 1990s, with a particular focus on electrical resonators. These electrical resonators require only a capacitive sensor and a coil to operate, and can be interrogated magnetically. Mechanical resonators, however, have not been intensively investigated for stand-alone sensing purposes.

[0148] The scientific literature is full of discussion of electrical and mechanical resonance and resonators. The engineering literature has several well recognized instances, the most prominent one being the class of resonant pressure sensors in silicon microsensors. Incidentally, these resonant pressure sensors are known to have sensitivity and stability at least an order of magnitude great than piezoresistive and capacitive sensors. In this class, a micro-beam lies on a deflecting diaphragm and is induced into resonance. Pressure deflects the diaphragm and changes the strain on the beam, whose resonance frequency then shifts. This shift is monitored by piezoresistors on the beam, which are then processed by circuitry on or near the transducer chip. An important aspect is that most declared resonant sensors operate similarly to this class of sensors and are not stand-alone, passive resonant sensors which can be wirelessly interrogated.

[0149] Significant intellectual property exists on the class of stand-alone, passive mechanical resonators. Included is an appendix table with examples of differences between the disclosed invention and the relevant patents. The significant point is that the inventions are largely undeveloped and, without a known exception, utilize a very different acoustic frequency range. The work in patents is done predominantly in the medical ultrasound range (MHz), whereas the disclosed invention here operates in the audible range (<20 kHz). Additionally, and related to this distinction, the method of interrogation of the patented inventions is frequently different from that of this disclosed invention.

[0150] Exemplary embodiments of the present disclosure provide numerous non-obvious advantages over existing systems. For example, the analytic solutions for resonance frequency of diaphragms and beams do not contain explicit pressure terms, and thus the pressure dependence is not obvious. Minor modifications of the formulas readily yield pressure dependence, but the insight to make them must first be had. In addition, the mechanism of sensing is fundamentally different from that of most silicon-based resonant pressure sensors. Most silicon-based resonant pressure sensors focus on inducing a pressure dependent strain on a resonating beam. This is typically done by deflecting the mechanical base on which the beam lies, or by deflecting another mechanical member onto the beam. IE, the resonance frequency of the sensing element is not directly shifted by local pressure. In our case, resonance frequency of our disclosed invention is directly shifted by local pressure.

[0151] Furthermore, the acoustic frequency range of the disclosed invention is fully audible (<20 kHz) rather than very high ultrasound (MHz). The largely undeveloped inventions covered in the scientific and patent literature typically operate in the medical ultrasound frequency range, which is 2 to 4 orders of magnitude higher than that of the disclosed invention here. The interrogation systems for this prior art are typically standard medical ultrasound probes, which limits the frequency range of the implantable sensors. Additionally, embodiments of the disclosed invention are only sensitive to low levels (several 100 mmHg) of gauge pressure across the diaphragm. That is, silicon transducers with diaphragms over vacuum sealed chambers (most of them) will not exhibit significant pressure dependence of their resonance frequency; at sensing levels, gauge pressure across the diaphragm is >800 mmHg. For example, the theory of the disclosed invention must be understood, and additionally, an off the shelf transducer cannot be used to empirically validate that theory.

[0152] To date, numerous systems exist for attempting to measure intravascular blood pressure, but all have significant limitations. For implantable devices, miniaturization and powering are the key limitations. For noninvasive devices (optical, tonometry), blood pressure waveforms can easily be generated, but scaling them with accurate systolic and diastolic values has been a persistent challenge.

[0153] Embodiments of the disclosed invention offer a solution, by providing simple passive sensor which can be anchored onto stent-like structure and be acoustically interrogated. The sensor can be made extremely small (low micron), and can be made of extremely stable ceramics (SiO2) to confer long term sensing stability. Additionally, the device has strong pressure sensitivity, enabling tenths of mmHg to be accurately measured

[0154] In one example, a mechanical resonator can be configured as an implantable blood pressure sensor capable of measuring varying low, medium, and high pressure ranges and operating in one of the wireless modalities shown in FIG. 47.

[0155] FIG. 48(a) illustrates a coordinate system, while FIG. 48(b) provides an illustration for an analytical model. In this example, 2a=length of square diaphragm; t=thickness; d=deflection.

Analytic Expression for Resonance Frequency

[0156] In an air environment, the analytical solution for the natural resonance frequency of a square plate with clamped edges

[00003]$\begin{array}{cc}{f}_0=\frac{36}{2.Math.}.Math.\sqrt{\left(\frac{D}{a^4}\right).Math.\left(\frac{1}{q}\right)}& \left(11.Math.a\right)\end{array}$

where

[00004]$D=\frac{{\mathrm{Et}}^3}{12.Math.\left(1-v^2\right)}$

is the flexural rigidity of the diaphragm, a is the square diaphragm length and q is the load on the diaphragm including its weight per unit area and applied pressure. Here, the spring constant of the diaphragm is

[00005]$K=\sqrt{\left(\frac{324.Math.D}{{}^2.Math.a^4}\right)}.$

[0157] FIGS. 49-51 show an experimental setup used to obtain results previously shown in FIGS. 41-43, and FIGS. 52-53 illustrate frequency versus pressure data obtained prototyping and development in the audible range.

[0158] FIGS. 54-55 illustrate the high penetration of audible acoustic waves in soft tissue. FIG. 54 demonstrates ultrasound attenuation occurs exponentially with penetration depth, and increases with increased frequency. The curves show the relative intensity of ultrasound at a particular frequency as a function of penetration depth in a medium with an attenuation coefficient of (0.5 db/cm)/MHz. The total distance traveled by the ultrasound pulse and echo is twice the penetration depth.

[0159] FIG. 55 demonstrates an attenuation function of a phantom measured using the pulse-echo substitution method. As shown, in the frequency range of 1.2 to 4.4 MHz, the least squares line is y=0.0767+0.692 x. The linear correlation coefficient is 0.9996. FIG. 56 is a chart showing the high level of acoustic energy that can be delivered to the resonator for different materials. FIG. 57 shows the reflected pressure ratio and reflected power ratio for soft tissue in combination with glass, stainless steel, and air, where:

[00006]$\mathrm{Reflected}.Math..Math.\mathrm{Pressure}=\frac{Z_2-Z_1}{Z_2+Z_1}$$\mathrm{Reflected}.Math..Math.\mathrm{Intensity}\left(\frac{\mathrm{Power}}{\mathrm{Area}}\right)={\left(\mathrm{Reflected}.Math..Math.\mathrm{Pressure}\right)}^2$

[0160] FIGS. 58-60 illustrate a schematic of an experimental set up for ultrasonic measurements and data obtained from the experiment, as disclosed in M. W. Borner et. al., Sensors and Actuators A 46-47 (1995) 62-65. FIG. 58 illustrates the schematic for the measurements, while FIG. 59 illustrates amplitude versus time data for (a) a micromembranes supported by a nickel honeycomb structure; (b) a membrane without the microstructure; and (c) the honeycomb structure alone. As shown in the figure, the echo from the micromembranes consists of two parts, with the first representing the initial signal and the second part attributed to vibrations of the membranes. As shown, echoes from the membrane or microstructure alone do not show the second part of the signal. FIG. 60 shows a Fourier transform of the signal, where the resonance frequency of the micromembranes can be seen.

[0161] As demonstrated herein, resonators used as implantable sensors provide numerous advantages, including no on-site power source or circuitry requirements, very small, and a robust design. Mechanical resonators provide numerous advantages (e.g. over electrical resonators), including the fact that non-electrical, extremely small mechanical resonator sensors can be implanted. In addition, mechanical resonators provide incredible sensitivity, given how sensitive mechanical resonance is to external pressure, and can be tailored to specific pressure ranges. Mechanical resonators theoretically excellent readout range given how well acoustic signals travel through the body. In addition, mechanical resonators have much more sensing stability over time, again because electronics are not necessary, and an elastic ceramic (quartz, glass, silicon, whatever) will not plastically deform over time. Furthermore, mechanical resonators provide for pulsewave recreation because the resonance frequency is high enough to permit dozens of samples per second in an unoptimized sensor, and possibly hundreds per second in an optimized sensor.

[0162] In addition, mechanical resonators provide audible acoustic (<10 kHz) interrogation rather than ultrasound and inexpensive piezoelectrics can be used instead of expensive ultrasound crystals and devices. Mechanical resonators provide much simpler readout electronics with inexpensive piezoelctrics and without frequency sweeps utilizing a simple, one-time acoustic pulse and then listen for the resonance echo. Furthermore, mechanical resonators can be configured with a very small size (m range in any dimension). In certain embodiments, mechanical resonators can be sized small enough to be coupled to a stent and/or for percutaneous delivery to implantation size.

[0163] All of the apparatus, devices, systems and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the devices, systems and methods of this invention have been described in terms of particular embodiments, it will be apparent to those of skill in the art that variations may be applied to the devices, systems and/or methods in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

REFERENCES

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