Ultrasonic sensing and imaging based on Whispering Gallery Mode (WGM) microresonators

Abstract

Optical whispering gallery mode (WGM) resonator-based acoustic sensors, imaging systems using acoustic sensors, and methods for detecting ultrasound using acoustic sensors are disclosed.

Description

Technology Field

[0001] Cross-reference regarding related applications

[0002] This application claims priority to U.S. provisional application serial number 62 / 901,883 filed on September 18, 2019, the entirety of which is incorporated herein by reference.

[0003] Statement regarding federal government-sponsored research or development

[0004] The present invention was made with government support under W911NF1710189 and W911NF1210026 granted by the Army Research Office. The government holds specific rights in the present invention.

[0005] Field of disclosure

[0006] The present disclosure relates to systems and methods for performing ultrasound imaging using acoustic transducers, generally comprising whispering-gallery-mode resonators. Background Technology

[0007] Ultrasound technology has attracted increasing interest in various fields, particularly in non-invasive measurements, remote sensing, and biomedical imaging. Ultrasound imaging is utilized in a wide variety of settings to non-invasively image patients' internal structures by detecting ultrasound pulses reflected from tissue boundaries within the patient. Ultrasound detectors used in imaging applications typically feature capabilities at high frequencies with low noise equivalent pressure (NEP) and wide bandwidths. Currently available piezoelectric-based ultrasound detectors generally satisfy these requirements. However, for imaging applications requiring detectors with smaller dimensions, the use of piezoelectric-based ultrasound detectors is limited by noise, in that the reduction in dimensions of smaller detectors entails an increase in noise associated with ultrasound detection.

[0008] In addition, as the resolution of the ultrasound increases by applying higher frequency sound waves, the penetration depth decreases due to increased acoustic attenuation. This trade-off between resolution and penetration depth poses a challenge in the context of conventional piezoelectric ultrasonic sensors.

[0009] Photonic devices (e.g., gratings, etalons, etc.) and optical pressure detection technologies are receiving increasing attention because they demonstrate great potential for ultrasonic detection and can be fabricated at micro-scales without sacrificing ultrasonic detection performance or sensitivity. In photonic devices, refractive index modulation and / or shape deformations caused by strain induced by acoustic waves are converted into changes in the intensity of the detected light or in the spectral characteristics of the device. In some existing devices, optical resonators have been used as highly sensitive ultrasonic detectors. In these resonators, the arrival of ultrasound leads to modulation of the resonant frequency or transmitted light intensity. Generally, the performance of an optical resonator is limited by its quality factor Q (i.e., the higher the Q, the lower the optical loss and the smaller the detectable resonance shift), as well as by the acousto-optical and mechanical properties of the material from which the resonator is made.

[0010] Other purposes and features will be partially clear and are explained in part below.

[0011] Brief description of the disclosure

[0012] In one embodiment, an acoustic sensor is disclosed comprising an optical whispering gallery mode resonator, a coupling waveguide for optically coupling to the resonator, and a polymer encasing a portion of the coupling waveguide and the resonator. The coupling waveguide is spaced apart from the resonator by a separation gap. Each of the resonator and the coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer.

[0013] In other embodiments, an acoustic sensing system is disclosed comprising an optical whispering gallery mode resonator, a coupling waveguide for optically coupling to the resonator, a polymer encapsulating portions of the resonator and the coupling waveguide, a light source coupled to a first end of the coupling waveguide protruding from a low-index polymer, and a photodetector coupled to a second end of the coupling waveguide and protruding from the low-index polymer. The coupling waveguide has a first end and a second end opposite to the first end and is spaced apart from the resonator by a separation gap. Each of the resonator and the coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer.

[0014] In additional embodiments, a photoacoustic imaging device comprising an acoustic sensor is disclosed. The acoustic sensor comprises an optical whispering gallery mode resonator, a coupling waveguide for optically coupling to the resonator, a polymer encapsulating portions of the resonator and the coupling waveguide, a transducer light source coupled to a first end of the coupling waveguide protruding from the low-exponential polymer, a transducer photodetector coupled to a second end of the coupling waveguide opposite to the first end and protruding from the low-exponential polymer, and a photoacoustic light source. The coupling waveguide has a first end and a second end opposite to the first end, and the coupling waveguide is spaced apart from the resonator by a separation gap. Each of the resonator and the coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer.

[0015] In other additional embodiments, a method for detecting ultrasound is disclosed, comprising the step of providing an acoustic sensing system. The acoustic sensing system comprises an optical whispering gallery mode resonator, a coupling waveguide for optically coupling to the resonator, a polymer enclosing portions of the resonator and the coupling waveguide, a light source, and a photodetector. The coupling waveguide has a first end and a second end opposite to the first end, and the coupling waveguide is spaced apart from the resonator by a separation gap. The light source is coupled to the first end of the coupling waveguide protruding from the low-exponential polymer, and the photodetector is coupled to the second end of the coupling waveguide protruding from the low-exponential polymer. The polymer forms a sample contact surface. Each of the resonator and the coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer. The method further comprises the steps of: acoustically coupling a sample contact surface to a sample so that ultrasonic waves emitted from within the sample are conducted through a polymer to a portion of a resonator and a coupling waveguide; introducing light generated by a light source to a first end of the coupling waveguide; converting light from a second end of the coupling waveguide, detected by a photodetector, into detector signals encoding the amplitude of the detected light; and converting the detector signals into pressure using a predetermined calibration rule.

[0016] Other purposes and features will be partially clear and are explained in part below. Brief explanation of the drawing

[0017] A person skilled in the art will understand that the drawings described below are for illustrative purposes only. The drawings are not intended to limit the scope of this teaching in any way. Figure 1a is a graph summarizing the fiber mode index as a function of wavelength for several different diameters of optical fibers in air. Figure 1b is a map showing the fiber mode distribution for the 1.6 μm optical fiber shown in Figure 1a. Figure 1c is a graph summarizing the fiber mode index as a function of wavelength for several different diameters of optical fibers in a polymer having a refractive index (n) of 1.33. Figure 1d is a map showing the fiber mode distribution for the 1.6 μm optical fiber shown in Figure 1c. FIG. 2a is an optical fiber (n) enclosed in a polymer having a refractive index (n) of 1.33. fiber ) and microtoroid resonator (m WGM,tr This is a graph summarizing the effective indices for optical transmission at 883 nm within ). Figure 2b is a map illustrating the fiber mode distribution for the optical fiber shown in Figure 2a. FIG. 2c is an optical fiber (n) enclosed in a polymer having a refractive index (n) of 1.33. fiber ) and microtoroid resonator (m WGM,tr This is a graph summarizing the effective indices for optical transmission at 778nm within ). Figure 2d is a map illustrating the fiber mode distribution for the optical fiber shown in Figure 2c. FIG. 2e is an optical fiber (n) enclosed in a polymer having a refractive index (n) of 1.33. fiber ) and microtoroid resonator (m WGM,tr This is a graph summarizing the effective indices for optical transmission at 709nm within ). Figure 2f is a map illustrating the fiber mode distribution for the optical fiber shown in Figure 2e. FIG. 3 is an image of an optical-resonator-based acoustic pressure sensor according to one embodiment of the present disclosure. FIG. 4a is a schematic cross-sectional view of the optical resonator-based acoustic sensor shown in FIG. 3, in which the optical resonator-based acoustic pressure sensor is embedded within a case formed of a low-exponential polymer material. FIG. 4b is a schematic side view of the built-in optical resonator-based acoustic sensor of FIG. 4a. FIG. 5 is a drawing of an acoustic imaging system including an optical resonator-based acoustic sensing probe according to one embodiment of the present disclosure. Figure 6 is a spectrum of light intensity transmitted through an optical resonator-based acoustic sensing probe as a function of the transmitted light wavelength. Figure 7 is a graph illustrating an example of a signal generated by an optical resonator-based acoustic sensing probe in response to an ultrasonic pulse. FIG. 8 is a block diagram schematically illustrating a system according to one embodiment of the present disclosure. FIG. 9 is a block diagram schematically illustrating a computing device according to one embodiment of the present disclosure. FIG. 10 is a block diagram schematically illustrating a remote or user computing device according to one embodiment of the present disclosure. FIG. 11 is a block diagram schematically illustrating a server system according to one embodiment of the present disclosure. FIG. 12 is a schematic diagram illustrating a method for manufacturing a microtoroidal resonator according to one embodiment of the present disclosure. FIG. 13a is a schematic side view illustrating a method of assembling an acoustic sensor according to one embodiment of the present disclosure. FIG. 13b is a schematic plan view illustrating a method of assembling an acoustic sensor according to one embodiment of the present disclosure. FIG. 14 is a screenshot illustrating a display of a portable device for obtaining transmission readings from an optical acoustic sensor according to one embodiment of the present disclosure. FIG. 15 is a schematic diagram illustrating elements of an ultrasonic imaging system including an optical resonator-based acoustic sensor according to one embodiment of the present disclosure. Figure 16a is a graph summarizing the sensitivity loading factor for gap detuning from critical coupling of an optical resonator-based acoustic sensor in air. Figure 16b is a graph summarizing the sensitivity loading factor for gap detuning from critical coupling of an optical resonator-based acoustic sensor encapsulated in a polymer n=1.33. FIG. 17a is a graph showing the penetration depth of an ultrasonic sensor as a function of ultrasonic frequency for various sensor enhancements made possible by the integration of an optical resonator-based acoustic sensor with various sensor enhancements in a tissue sample representing fat or breast tissue. FIG. 17b is a graph showing the penetration depth of an ultrasonic sensor as a function of ultrasonic frequency for various sensor enhancements made possible by the integration of an optical resonator-based acoustic sensor with various sensor enhancements in a tissue sample representing blood. Figure 18a is a graph summarizing various conventional imaging modes (OCT / optical coherence tomography, PAT / photoacoustic tomography, US / ultrasound, and MRI / magnetic resonance imaging) mapped as a function of image resolution and penetration depth. FIG. 18b is a graph corresponding to the graph of FIG. 18a illustrating the effect of improved sensitivity provided by optical resonator-based acoustic sensors in various imaging aspects according to an embodiment of the present disclosure. FIG. 19 is an optical microscope image showing a single microtoroid sensor according to an embodiment of the present disclosure. Figure 20a is a graph summarizing the signal measured by a polymer-encapsulated microtoroid pressure sensor in response to 5 MHz ultrasonic pulses delivered at various pressures. FIG. 20b is a graph summarizing the signal measured by a polymer-encapsulated microtoroid pressure sensor in response to 20 MHz ultrasonic pulses delivered at various pressures. Figure 21 is a graph summarizing the signal amplitude obtained using a polymer-encapsulated microtoroidal pressure sensor as a function of frequency detuning used to evaluate the SNR for the polymer-encapsulated microtoroidal pressure sensor. Figure 22 is a graph showing normalized signal amplitudes obtained by a polymer-encapsulated microtoroid pressure sensor that detects ultrasonic pulses transmitted in a range of frequencies. FIG. 23a is a schematic diagram illustrating a sign convention used to quantify the direction of incident sound waves onto the surface of a polymer-encapsulated microtoroidal pressure sensor. FIG. 23b is a map of normalized signal intensity obtained by a polymer-encapsulated microtoroid pressure sensor that detects ultrasonic pulses transmitted in a range of incident sound angles as defined in FIG. 23a. FIG. 24 is a schematic diagram of the detection of acoustic signals using a microtoroidal pressure sensor according to one embodiment of the present disclosure. FIG. 25 includes graphs showing wavelength detuning and transmission within the resonator during wavelength up-scanning of the resonator. FIG. 26 is a schematic diagram of a photoacoustic imaging system according to one embodiment of the present disclosure. Although the arrangements currently under discussion are illustrated in the drawings, it is understood that the embodiments are not limited to the exact arrangements and are merely the means illustrated. While numerous embodiments are disclosed, other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description, which illustrates and describes exemplary aspects of the present disclosure. As is recognized, the present invention may be modified in various aspects without departing from the spirit and scope of the present disclosure. Accordingly, the drawings and the detailed description should be regarded as illustrative in nature and are not limiting. Specific details for implementing the invention

[0018] In various embodiments, a pressure sensor comprising an ultra-high quality optical whispering gallery mode (WGM) resonator encapsulated in a low-exponential polymer is disclosed. In various other embodiments, the polymer-encapsulated whispering gallery mode (WGM) resonator may be included in a pressure detection system. In various additional embodiments, a medical imaging system, including but not limited to an ultrasonic imaging system, may include an optical whispering gallery mode (WGM) resonator as an acoustic sensor. Compared to conventional hydrophones based on piezoelectric materials, the optical resonator can leverage the high sensitivity of circulating light to mechanical perturbations induced by incoming acoustic waves, and thus achieve higher sensitivity to acoustic signals. Meanwhile, the sub-millimeter footprint achievable using WGM microresonators provides (1) the possibility of forming compact sensor arrays; and (2) the acoustic response bandwidth can be widened to higher frequencies.

[0019] In various embodiments, polymer-encapsulated WGM resonators have high optical quality factors (Q~10) that respond to input acoustic signals, as described in more detail below.7 It has both ) and rich mechanical modes. The polymer casing holds the fiber taper and WGM resonator coupled in a fixed arrangement, enabling robust optical driving of the system without mechanical perturbation. The polymer casing further simplifies the optical packaging process during manufacturing, and the packaging simplifies the integration of polymer-encapsulated WGM resonators as pressure sensors into the design of various devices, including but not limited to ultrasonic imaging systems.

[0020] I. Optical Resonator-Based Acoustic Sensors, Sensor Systems, and Methods of Use

[0021] Details of the present invention and various embodiments can be better understood by referring to the drawings. Referring to FIG. 3, an example of an optical resonator-based acoustic sensor system (100) is illustrated. In various embodiments, the system (100) may include a light source (101) which includes, but is not limited to, a tunable laser. The system (100) further includes a WGM resonator (102) attached to a substrate (113), and a coupling waveguide (104) for bringing laser energy into and out of the resonant modes of the resonator (102). The system (100) may further include an optical coupler (103) configured to direct the laser energy generated by the light source (101) into the coupling waveguide (104). Non-limiting examples of suitable light sources include semiconductor lasers (DFB or FP laser diodes) whose wavelength can be finely tuned by controlling the temperature or by controlling the driving current, GaN or similar LED on-chip light sources, or on-chip WGM microlasers. A photoreceiver (106) (or photodetector) coupled to opposite ends of the coupled waveguide (104) can be used to detect a laser signal (108) at the output port (110) of the coupled waveguide (104).

[0022] In various embodiments, both the light source (101) and the light receiver (106) are linked to a computing device (112) (not shown). In various embodiments, the computing device is configured to control the operation of the light source (112) and to process the output from the light receiver (106) to extract information related to the light transmission from the resonator (102). In another embodiment, the computing device (112) of the system (100) further includes a processor and a non-volatile computer-readable memory (not shown), as described in more detail below.

[0023] FIGS. 4a and FIGS. 4b are cross-sectional and side schematic diagrams of a system (100) similar to the system illustrated in FIG. 3, in which a portion (114) of the WGM resonator (102) and the coupling waveguide (104) is enclosed in a low-exponential polymer (116), respectively. In one embodiment, the low-exponential polymer (116) holds the portion (114) of the coupling waveguide (104) and the WGM resonator (102) in a fixed arrangement. In some embodiments, the fixed arrangement may include a gap (118) separating the coupling waveguide (104) from the WGM resonator (102). In one embodiment, the gap (118) is selected to result in critical coupling of laser energy directed to the WGM resonator (102) through the coupling waveguide (104). In another embodiment, the gap (118) is slightly offset from the critical coupling gap distance, enabling the operation of the WGM resonator (102) closer to the maximum load factor associated with enhanced sensor sensitivity, as described in more detail below.

[0024] In various embodiments, the selected value of the gap is influenced by any one or more of a plurality of factors, including but not limited to the dimensions and materials of the optical WGM resonator, the dimensions and materials of the coupled waveguide, the dimensions and materials of the encapsulating polymer, the operating parameters of the optical WGM vibrator-based pressure sensor, and any other relevant factors. A detailed description of the relationship of at least some of the factors described above is described in more detail below.

[0025] Referring again to FIGS. 4a and 4b, the low-exponential polymer (116) is configured not only to efficiently transmit light between the coupling waveguide (104) and the WGM resonator (102), but also to efficiently receive ultrasounds from the tissue being imaged using an ultrasound imaging system, as described in more detail below. In various embodiments, the low-exponential polymer (116) is applied in an uncured state over the WGM resonator (102), the coupling waveguide (104), and the substrate (113), and subsequently cured in situ using a curing method. Any known curing method may be used to cure the low-exponential polymer (116) without limitation, as long as the curing method is compatible with the selected polymer material. Non-limiting examples of suitable curing methods include UV curing, moisture curing, and cross-link curing. In some embodiments, the degree of curing may be varied to modulate the acoustic impedance and / or refractive index of the low-index polymer (116) to levels that enable efficient operation of the system (100), as described in more detail below. As a non-limiting example, the curing method may produce a cured polymer characterized by a refractive index suitable for efficient light transmission between the WGM resonator (102) and the coupled waveguide (104), as well as a mechanical index that matches the tissue being ultrasound-imaging. Without being limited to any specific theory, the mechanical matching of the low-index polymer (116) to the tissue may facilitate the efficient transmission of ultrasound pulses from the imaged tissue.

[0026] In other embodiments, the low-index polymer (116) may be covered with an additional membrane layer (120). In various embodiments, the membrane layer (120) is selected to seal the underlying polymer (116) to provide a barrier preventing oxygen from coming into contact with the polymer (116), thereby facilitating a curing process, such as the UV curing process described in more detail below. In some embodiments, the membrane layer (120) may be removed from the low-index polymer (116) of the system (100) upon completion of the curing process. In other embodiments, the membrane layer (120) may be retained over an exposed surface of the low-index polymer (116). In these other embodiments, the material of the membrane layer (120) may be selected to be acoustically matched to the tissue to be imaged using an ultrasonic imaging system including a sensor system (100), as described in more detail below.

[0027] In various embodiments, the membrane layer (120) is any suitable material capable of preventing oxygen from penetrating into the underlying low-index polymer layer (116). Non-limiting examples of suitable membrane layer materials include cover slips, polymer layers, and any other suitable membrane material. Without being limited to any specific theory, the refractive index of the membrane layer does not affect the performance of the encapsulated WGM resonator (102) and coupled waveguide (104) described herein. In some embodiments, the membrane layer (120) may be created using a material that is acoustically matched to the tissue to be imaged, as described above.

[0028] In various embodiments, the membrane layer (120) may be pre-formed and applied over the low-index polymer (116), or the membrane layer (120) may be applied over the low-index polymer (116) in an uncured state and cured in place. As a non-limiting example, applying a pre-formed membrane layer over the low-index polymer may facilitate the subsequent removal of the membrane layer upon completion of curing within the low-index polymer as described above. As another non-limiting example, an acoustically matched membrane material may be applied and cured in place to the tissue to be imaged to improve the affinity of contact between the membrane layer and the low-index polymer, thereby facilitating the efficient transmission of acoustic signals from the tissue to the underlying sensors.

[0029] In various embodiments, the thickness of the membrane layer is in the range of about 0.1 mm to about 5 mm. In various other embodiments, the thickness of the membrane layer is in the range of about 0.1 mm to about 0.3 mm, about 0.2 mm to about 0.4 mm, about 0.3 mm to about 0.5 mm, about 0.5 mm to about 0.7 mm, about 0.6 mm to about 0.8 mm, about 0.7 mm to about 0.9 mm, about 0.8 mm to about 1.0 mm, about 0.9 mm to about 1.1 mm, about 1.0 mm to about 2 mm, about 1.5 mm to about 2.5 mm, about 2 mm to about 3 mm, about 2.5 mm to about 3.5 mm, about 3 mm to about 4 mm, about 3.5 mm to about 4.5 mm, and about 4 mm to about 5 mm.

[0030] FIG. 4b is a side view of the system (100) illustrated in FIG. 4a. As illustrated in FIG. 4b, the ends of the coupling waveguide (104) adjacent to the enclosed portion (114) protrude from the low-index polymer encasement (116) to enable coupling of the light source (101) to the coupling waveguide (104) via an optical coupler (103) and to enable coupling of the coupling waveguide (104) to a photodetector (106). The photodetector (106) is configured to detect a laser signal output at the output port (110) of the coupling waveguide (104) and to transmit a detector output signal (122) indicating the detected laser signal output.

[0031] In various embodiments, the computing device (112) is further configured to operate the optical resonator-based acoustic sensor system (100) in scanning mode to select an operating wavelength, as well as to operate the locked system (100) in an operating wavelength to detect acoustic signals as described in more detail below. In one embodiment, the computing device (112) is further configured to control and tune a light source to scan wavelengths introduced into the coupled waveguide (104), as well as to perform a selection algorithm to analyze the transmission spectrum of the detector output signal to derive a detected polarization value, and to select a matching polarization value from a plurality of polarization values ​​as described in more detail below.

[0032] In various embodiments, the optical resonator may be characterized by a diameter in the range of about 50 μm to about 200 μm. In various other embodiments, the diameter of the resonator is about 50 μm to about 60 μm, about 55 μm to about 65 μm, about 60 μm to about 70 μm, about 65 μm to about 75 μm, about 70 μm to about 80 μm, about 75 μm to about 85 μm, about 80 μm to about 90 μm, about 85 μm to about 95 μm, about 90 μm to about 100 μm, about 95 μm to about 105 μm, about 100 μm to about 120 μm, about 110 μm to about 130 μm, about 120 μm to about 140 μm, about 130 μm to about 150 μm, about 140 μm to about 160 μm, about 150 μm to about The ranges are 170 μm, about 160 μm to about 180 μm, about 170 μm to about 190 μm, and about 180 μm to about 200 μm.

[0033] Without being limited to any specific theory, the diameter of the optical resonator can affect at least one of a plurality of factors related to the performance of an optical resonator-based pressure sensor, including but not limited to the resonant wavelengths and center frequencies of the pressure sensor.

[0034] In various other embodiments, the coupling waveguide may include any suitable waveguide without limitation. In one embodiment, the coupling waveguide is a tapered fiber. In various embodiments, the minimum diameter of the tapered fiber is in the range of about 0.5 μm to about 5 μm. In various other embodiments, the minimum diameter of the tapered fiber is in the range of about 0.5 μm to about 0.7 μm, about 0.6 μm to about 0.8 μm, about 0.7 μm to about 0.9 μm, about 0.8 μm to about 1.0 μm, about 0.9 μm to about 1.1 μm, about 1 μm to about 2 μm, about 1.5 μm to about 2.5 μm, about 2 μm to about 3 μm, about 2.5 μm to about 3.5 μm, about 3 μm to about 4 μm, about 3.5 μm to about 4.5 μm, and about 4 μm to about 5 μm. Without being limited to any particular theory, smaller tapered diameters are thought to optimize the coupling of shorter optical wavelengths onto the WGM resonators of the disclosed acoustic sensors as described herein.

[0035] In one embodiment, the coupled waveguide comprises a tapered fiber having a minimum diameter of at least 1.5 μm, a taper length of about 2 cm, and a fiber end diameter of about 125 μm. In various additional embodiments, the coupled waveguides may be composed of any suitable material known in the art, including but not limited to fused silica material, low-loss optical polymer, and any other suitable material.

[0036] In various embodiments, the performance of WGM resonator-based acoustic sensors can be evaluated without limitation using any suitable existing analysis method. In one embodiment, measurements of ultrasonic amplitudes acquired by a toroidal resonator-based acoustic sensor can be analyzed using standard methods as shown in FIG. 21 to evaluate the SNR and noise equivalent pressure. In another embodiment, measurements of response amplitudes of the toroidal resonator-based acoustic sensor over a range of ultrasonic pressures can be analyzed using standard methods to determine the sensitivity of the sensor at different frequencies of ultrasound. As a non-limiting example, signal amplitudes of a toroidal resonator-based acoustic sensor responding to 5 MHz and 20 MHz ultrasounds at different wave pressures are shown in FIG. 20a and 20b, respectively. In an additional embodiment, measurements of response amplitudes of the toroidal resonator-based acoustic sensor over a range of ultrasonic frequencies can be analyzed using standard methods to determine the bandwidth of the sensor as shown in FIG. 22. The acoustic sensing performance of an acoustic sensor comprising a polymer-encapsulated WGM resonator as described in this specification is summarized in Table 1:

[0037] Table 1: Performance of acoustic sensors with enclosed WGM resonators

[0038]

[0039] As another non-limiting example, the acoustic sensing performance of the acoustic sensor characterized in Table 1 is compared with the corresponding performance of the conventional piezoelectric transducer in Table 2 below:

[0040] Table 2: Comparison of acoustic sensor performance between enclosed WGM resonators and conventional medical-grade ultrasound devices

[0041]

[0042] Referring again to FIG. 6, the transmission spectrum obtained from the high-Q WGM typically has a Lorentzian line shape. As illustrated in FIG. 24, the incoming ultrasound can induce refractive index modulation and / or shape deformation (refer to the left images in FIG. 24), which is converted into a resonant shift in the transmission spectrum (refer to the right graph in FIG. 24). If the operating wavelength is fixed, variations in the resonant frequency are reflected as oscillations of the transmitted optical power over time (refer to the output power signal in the right graph of FIG. 24). In one embodiment, to maximize the amplitude of the output oscillations induced by the incoming ultrasound, the operating wavelength is set to a wavelength corresponding to a point (2402) on the transmission spectrum having the greatest slope.

[0043] It should be noted that only the thermal stability side is preferred. Without being limited to any specific theory, the thermal stability side is either the shorter wavelength side or the longer wavelength side depending on at least one factor, which includes but is not limited to the material-related thermo-optical coefficient of the resonator. If the thermo-optical coefficient of the resonator is dominated by dielectric materials, including but not limited to silica, silicon, and silicon nitride, which are characterized by positive thermo-optical coefficients, the shorter wavelength side (region (606) in FIG. 6) is thermally stable. If the thermo-optical coefficient of the resonator is dominated by polymer materials, which are characterized by negative thermo-optical coefficients, the longer wavelength side (region (608) in FIG. 6) is thermally stable.

[0044] As illustrated in FIG. 25, the thermally stable region in the transmission spectrum of a high-Q microresonator is identified as having a triangular shape (2502) during wavelength scanning processes. As a non-limiting example, for a high-Q silica microresonator made of dielectric materials having positive thermo-optical coefficients (dn / dT > 0), as the wavelength of the pump laser approaches the resonant wavelength during the wavelength up-scanning process, the cavity begins to heat up, and this heat shifts the resonant wavelength, causing the tracking process between the resonant wavelength and the scanning pump wavelength to up-scan, that is, both the resonant wavelength and the scanning pump wavelength shift in the same direction. Specifically, both the resonant and pump wavelengths increase linearly, while the wavelength detuning between them decreases linearly. In this tracking process, the pump wavelength (shown as a dashed line in the upper graph of FIG. 25) tracks the moving resonant wavelength (shown as a solid line in the upper graph of FIG. 25), and the detuning between them is within the bandwidth of the resonance. Thus, the resonator operates in the resonant state, and the pump laser energy is coupled to the resonator. This tracking process continues until the pump wavelength catches up to the resonant wavelength. Beyond this point, the resonant state is rapidly lost in the region (2504) of the moving resonant wavelength because the pump laser can no longer push the resonant wavelength further.

[0045] It should be noted that the thermal stability region can be identified during wavelength up-scanning (see FIG. 25) for resonator materials having positive thermo-optical coefficients as described above, or during wavelength down-scanning (not shown) for resonator materials having negative thermo-optical coefficients. When the thermo-optical coefficient of the resonator is dominated by dielectric materials such as silica, silicon, and silicon nitride, where the thermo-optical coefficient > 0, the wavelength up-scanning side (shorter wavelength side) is thermally stable. When the thermo-optical coefficient of the resonator is dominated by polymers (thermo-optical coefficient < 0), the wavelength up-scanning side (longer wavelength side) is thermally stable.

[0046] a. Arrangement of resonators and optical fibers

[0047] In various embodiments, the dimensions and arrangement of the optical fiber and optical resonator are determined according to one or more rules, which include various factors related to the performance of the sensor. In one embodiment, the separation rule may be used to determine the gap separating the outer circumference of the tapered optical fiber and the optical resonator. In another embodiment, the dimensions and arrangement of the optical fiber and optical resonator may be influenced by a plurality of factors described below.

[0048] Without being limited to any specific theory, the dimensions of the fiber waveguide determine the effective indices of the waveguide modes, and the gap between the fiber taper and the resonator determines the coupling strength, which can alternatively be quantified as the coupling-induced loss. An ideally excited WGM, also referred to herein as critically coupled, is characterized by a narrow and deep Lorentzian dip shape within the transmission spectrum of the coupled WGM and the fiber taper. This critical coupling is achieved when i) the effective indices of the fiber waveguide modes match the effective indices of the WGM, and ii) the coupling-induced loss is equal to the intrinsic loss within the resonator.

[0049] b. Determination of the Ideal Fiber Taper

[0050] In various embodiments, the ideal fiber taper for exciting optical modes in whispering gallery mode (WGM) microtoroid resonators is determined using various criteria described in more detail below.

[0051] In one embodiment, the ideal fiber taper must satisfy the phase matching condition with the target WGMs, as expressed as follows:

[0052] [Mathematical Formula 1]

[0053]

[0054] Here, n WGM,tr is the converted effective index (n) of WGM microtoroidal resonators WGM ) and; n fiber is determined by the diameter of the fiber taper and the refractive index; n WGM is determined by the size and refractive index of the resonator as well as the refractive index of the surrounding medium. In various embodiments, n fiber and n WGM Both can be numerically calculated using any suitable method known in the art, including but not limited to the finite element method (FEM).

[0055] n fiber :

[0056] In one embodiment, FEM mode analysis is applied to simulate the mode distribution and effective indices of fiber modes having different diameters and surrounding materials as shown in FIGS. 1a through 1d for several different taper diameters in air (Figs. 1a and 1b) and a low-index (n=1.3) polymer (Figs. 1c and 1d).

[0057] n WGM :

[0058] In an additional embodiment, FEM natural frequency analysis (2D rotational symmetry model) is applied to simulate the mode distributions and natural frequencies of WGM microtoroid resonators. In this embodiment, n WGM It is derived using the following mathematical formula:

[0059] [Mathematical Formula 2]

[0060]

[0061] Here, m is the azimuth mode number, c is the speed of light, ω is the simulated natural frequency, and R e is the radial position of the "mode center of mass" and is indicated as follows.

[0062] [Mathematical Formula 3]

[0063]

[0064] Here, E is the amplitude of the electric field, and n(r) is the refractive index.

[0065] n WGM,tr :

[0066] In a different mode, n WGM,tr is determined using the following formula:

[0067] [Mathematical Formula 4]

[0068]

[0069] Here, d sep is the distance between the WGM "mode center of mass" and the fiber center.

[0070] When the coupling gap is very small, that is, when the fiber taper is in near contact with the resonator, it becomes as follows:

[0071] [Mathematical Formula 5]

[0072]

[0073] Here, a and a f and are the minor radii of the microtoroid and fiber taper radii, respectively, and R pis the major radius of the microtoroid resonator.

[0074] FIGS. 2A, 2C, and 2E are effective indices n having variable fiber taper diameters at wavelengths of 883 nm, 778 nm, and 709 nm, respectively, generated using the aforementioned mathematical formulas and methods. WGM,tr and n fiber These are graphs summarizing [the details]. Figures 2b, 2d, and 2f are maps of fiber mode distributions for the optical fibers of Figures 2a, 2c, and 2e, respectively. Figures 2a, 2c, and 2e show that the ideal taper diameters for a polymer background are 1.41 μm, 1.31 μm, and 1.25 μm at wavelengths of 883 nm, 778 nm, and 709 nm, respectively.

[0075] c. Low-index polymer layer

[0076] In various embodiments, parts of the WGM resonator and coupled waveguide are enclosed in a low-exponential polymer material. The polymer encasement performs various functions related to manufacturing, integration into various devices such as ultrasonic imaging systems, and the use of WGM resonator-based optical pressure sensors for detecting pressures as described herein. In some embodiments, the polymer encasement performs a triple function: i) protecting the coupling region, 2) effectively transmitting the input acoustic signal, and iii) acting as a damping layer for the vibrating structure. The numerous functions performed by the encasement polymer impose constraints on the selection of the encasement polymer material and the dimensions of the polymer layer.

[0077] In one embodiment, the encasement polymer material is selected to enable rapid curing with minimal changes in refractive index and density. In another embodiment, the encasement polymer material is selected to be acoustically transparent to input signals, including but not limited to ultrasonic pulses emanating from tissue to be imaged using an ultrasonic or photoacoustic imaging system. In an additional embodiment, the acoustic signal transmitted to the WGM resonator-based pressure sensor can be enhanced by engineering the dimensions of the encasement polymer layer. In this additional embodiment, the thickness of the encasement layer can be set to (1 / 4 + n / 2) times the acoustic center wavelength, and / or a convex upper boundary can be formed within the polymer encasement layer to enhance acoustic focusing on the WGM resonator. In another additional embodiment, the encasement polymer material is selected to enhance the effective damping of mechanical vibrations of the resonator structure in response to received pressure pulses to eliminate the response tail for pulsed acoustic inputs.

[0078] In one exemplary embodiment, the encasement polymer material can be selected and engineered to improve sensor sensitivity by forming an encasement polymer layer as described above, while minimizing response tails caused by mechanical vibration or multiple reflections by selecting a polymer having an appropriate level of acoustic damping.

[0079] In various embodiments, the encasement polymer material may be a low-index polymer, defined herein as a polymer having a refractive index smaller than the corresponding refractive indices of the WGM resonator and coupled waveguide. Without being limited to any specific theory, the inclusion of the encasement polymer material results in an enhanced coupling-induced mode expansion of the WGM resonator and coupled waveguide compared to the equivalent system in air. As a non-limiting example, the fiber mode distribution for an optical fiber enclosed in a low-index polymer (see FIG. 1d) is wider than the corresponding fiber mode distribution for an optical fiber in air (see FIG. 1b). Consequently, the refractive index of the selected encasement polymer can improve the sensitivity of sensor performance for precise placement of the coupled fiber at the optimal gap separation distance, as described in more detail below. Without being limited to any specific theory, the refractive index contrast (n) described in more detail below contrast = n resonator / n polymer ) affects the Lorentzian line shape (Fig. 6) and load curve (Fig. 16b) of the WGM resonator. In particular, n contrast As α approaches 1, the Lorentzian line shape and load curve expand, and the Q factor decreases.

[0080] In various other embodiments, the acoustic impedance of the encasement polymer material can be matched to the corresponding acoustic impedance of the sample to be ultrasonically imaged using an ultrasonically imaging system comprising a WGM resonator-based pressure sensor. As a non-limiting example, PDMS is a polymer that has a relatively low degree of acoustic mismatch (approximately 2 times) with typical biological tissues. In various additional embodiments, the acoustic damping of the encasement polymer material can be selected to suppress internal echoing of ultrasounds within the encapsulated pressure sensor while maintaining efficient transmission of ultrasounds to the WGM resonator.

[0081] In various embodiments, any suitable optical polymer known in the art may be selected without limitation to be used as an encasement polymer. In various embodiments, the encasement polymer includes, but is not limited to, UV-cured polymers or water-cured polymers. Non-limiting examples of suitable encasement polymer materials include PDMS, PFOA, and non-PFOA type fluoro(meth)acrylates.

[0082] d. Center frequency

[0083] In various embodiments, the center frequency of the acoustic response band of a WGM-based sensor is determined by the intrinsic mechanical mode of the resonator. As a non-limiting example, in a microsphere, the mechanical resonance frequency for a mechanical mode of the same order is inversely proportional to the diameter of the microsphere resonator, consistent with theoretical predictions based on the free sphere model. As another non-limiting example, for chip-based microdisks or microtoroid resonators, the mechanical resonance frequency is approximately inversely proportional to the length of the free-standing disk membrane, i.e., the undercut size.

[0084] e. Bond gap

[0085] In various embodiments, the coupling gap of the WGM resonator-based pressure sensor is selected to enhance any one or more of at least several sensor performance parameters, including but not limited to critical coupling of the WGM resonator and the coupling waveguide, and sensor sensitivity.

[0086] Extension of coupled inductive modes, not limited to any specific theory Is It is found to be proportional to, where Is ( It is the field damping coefficient outside the resonator body (estimated by), and d is the width of the coupling gap. n in an air background contrast = n resonator and, in polymer packaging, n contrast = n resonator / n polymer am.

[0087] In some embodiments, the sensitivity of a WGM resonator-based pressure sensor is enhanced when a laser frequency is locked at the center of one side of the Lorentzian line shape of the WGM resonator, as shown in FIG. 16a for a sensor without encasement (air) and in FIG. 16b for a sensor with low-exponential polymer encasement. When thermally locked, the short-wavelength side is stable for materials (dielectric materials) having positive thermo-optical coefficients, whereas the long-wavelength side is stable for materials (polymers) having negative thermo-optical coefficients. Analytically, this can be expressed as follows:

[0088] [Mathematical Formula 6]

[0089]

[0090] [Mathematical Formula 7] and [Mathematical Formula 8]

[0091]

[0092] [Mathematical Formula 9]

[0093]

[0094] Here, Δω is the angular frequency detuning between the pump laser and the real-time resonance, and T is the observable transmission.

[0095] In other embodiments, ideal operation detuning occurs at the steepest slope in the transmission spectrum, allowing the small signal indicated by the resonant shift to be amplified the most. In addition, coupled induced This relates to the depth and width of the Lorentzian line shape of the transmission. As a non-limiting example, FIG. 6 is a graph of a transmission spectrum showing the depth (602), width (604), and maximum slope (606).

[0096] In one embodiment, the standard coupling criterion is defined as a "critical coupling," where And, the deepest line shape is achieved as a simple indicator of the full extension of the transmitted power. Because this exists—where △d is the gap width detuned from the gap of the critical coupling—, The theoretical sensitivity proportional to can be described as a function of △d:

[0097] [Mathematical Formula 10]

[0098]

[0099] By normalizing the sensitivity at the critical coupling, the load factor induced by the coupling is defined:

[0100] [Mathematical Formula 11]

[0101]

[0102] As shown in Figures 16a and 16b, the load factors at 780 nm in air and polymer (n=1.33) are respectively shown.

[0103] f. Microtoroid manufacturing method

[0104] In various embodiments, microtoroid WGM resonators may be fabricated on silicon wafers or any other suitable substrate using any suitable method known in the art. As a non-limiting example, FIG. 12 is a summary of a method for fabricating a microtoroid in one embodiment. Referring to FIG. 12, a silica layer is oxidized on a single-crystal silicon substrate (step 1), and HDMS is deposited on the silica layer by any suitable method, including but not limited to thermal evaporation and spin coating (step 2). In this embodiment, a UV mask is deposited on the photoresist and then UV exposed (step 3) to remove the photoresist that is not masked during development (step 4). The portion of the silica layer exposed by the removal of the photoresist is removed without limitation using any suitable method. Parts of the silicon substrate are removed using any suitable method to form a support column (step 6), and then a silica lip is formed around the perimeter of the silica layer by any known method, including but not limited to CO2 laser reflow (step 7), to complete the microtoroid. An image of the microtoroid prepared using the above method is provided in FIG. 19.

[0105] In various embodiments, the optical resonator may be provided in any suitable form including, but not limited to, microtoroids, microdisks, microrings, microspheres, and any other suitable form. In various other embodiments, the optical resonator may be composed of any suitable material including, but not limited to, silicon, silica, lithium niobite, and any other suitable material.

[0106] g. Sensor packaging method

[0107] In various embodiments, the optical WGM resonator-based acoustic sensor is characterized by having a submillimeter-level footprint, enabling the formation of compact sensor arrays. In some embodiments, the on-chip design of the optical WGM resonator-based acoustic sensor can be used to construct 1D or 2D sensor arrays with a period as small as 0.3 mm.

[0108] In one embodiment, the WGM resonators described herein may be manufactured on commercial silicon wafers using any suitable existing manufacturing method without limitation. In another embodiment, the cost of the sensors may be significantly reduced due to the compatibility of suitable manufacturing methods with current semiconductor industry manufacturing systems and methods.

[0109] As a non-limiting example, as illustrated in FIGS. 13a and 13b, microtoroid resonators (1302) are fabricated on a substrate (1312) having an engineered mechanical spectrum and lateral support walls. Tapered fibers (1304) having an optimal diameter are fabricated and positioned within an encapsulating polymer (1306) to combine the tapered fibers (1304) with the microtoroid (1302). In one embodiment, a fiber guide (1308) is fabricated on the substrate (1312) to facilitate the positioning of the tapered fibers (1304) adjacent to the microtoroid (1302). In this embodiment, the substrate (1312) may be coupled to an adjustable platform comprising, but not limited to, a platform and an attached fiber guide (1308) and a microtoroid (1302) configured to move the microstage or micromanipulator against the tapered fiber (1304).

[0110] In this embodiment, the microtoroid (1302) and the fiber (1304) are covered with a UV-curable low-index polymer as shown in FIGS. 13a and 13b. The polymer-covered microtoroid (1302) and the fiber guide (1308) are then moved to tune to an optimal bonding gap in the polymer by adjusting the gap (1310) between the microtoroid (1302) and the fiber (1304). In one embodiment, the optimal tuning gap can be identified by repeatedly acquiring transmission spectra using a computing device for different gap distances as shown in FIG. 14. When the microtoroid (1302) and the fiber (1304) are positioned at the desired gap as described above, the low-index polymer is directly exposed to UV light, and the real-time transmission spectrum is monitored as shown in FIG. 14 until an indication of curing of the bonding area is detected. In one embodiment, indication of curing of the bonding region includes a rapid shift of optical resonance in the transmission spectra. In another embodiment, the entire sensor device may be covered with a plastic film to establish an inert environment for UV curing the polymer layer. Within this inert environment, the entire encapsulated polymer layer may be cured in this embodiment.

[0111] In one embodiment, the driving system of the optical resonators illustrated in FIG. 14 may be provided as a phone-sized system. This phone-sized system may be used not only to evaluate device performance while deploying fibers and microtoroids, but also to operate pressure sensors in various devices as described herein.

[0112] II. Imaging Systems

[0113] In various embodiments, the aforementioned optical resonator-based acoustic sensors simultaneously achieve high sensitivity and wide bandwidth at levels unprecedented for previous acoustic sensor configurations. In some embodiments, at least one optical resonator-based acoustic sensor may serve as an acoustic detector in a clinical imaging system, including but not limited to an ultrasonic acoustic imaging system, a photothermal imaging system, and any other suitable clinical imaging system for detecting acoustic signals.

[0114] a. Ultrasound imaging systems

[0115] In one embodiment, optical resonator-based acoustic sensors are integrated within an ultrasound imaging system (1500) as illustrated in FIG. 15. In this embodiment, the optical resonator-based acoustic sensor (1502) replaces conventional piezoelectric transducers for detecting ultrasound in a probe array (1504), while retaining piezoelectric transducers within an ultrasound probe head (1506) to generate US pulses that are scattered, reflected, or otherwise altered by the imaged tissues. With enhanced sensitivity and extended bandwidth compared to conventional devices such as piezoelectric sensors, the optical resonator-based acoustic sensor (1502) collects sufficient information for image reconstruction even from ultrasound signals that are strongly attenuated at high frequencies. Consequently, the integration of the optical resonator-based acoustic sensor (1502) can help overcome the trade-off between resolution (determined frequency) and penetration depth for current clinical ultrasound systems.

[0116] In various embodiments, the ultrasonic imaging system generates ultrasounds of any frequency greater than about 20 kHz without limitation. As previously described, whisper gallery mode microresonators can be configured to detect a wide range of acoustic frequencies. In some embodiments, the ultrasonic imaging system uses waves having frequencies in the range of about 20 kHz to about 200 MHz or higher. In other embodiments, the ultrasonic imaging system uses waves having frequencies in the range of about 20 kHz to about 200 MHz or higher, including but not limited to the range of about 2 MHz to about 20 MHz used in conventional ultrasonic imaging systems, ultra-high frequency ultrasound in the range of about 100 MHz to about 300 MHz, and any other suitable ultrasonic frequencies. By enabling the use of high-frequency ultrasound for applications with deep penetration requirements, the disclosed optical resonator-based ultrasonic detector can significantly increase the resolution of ultrasonic imaging.

[0117] Referring again to FIG. 15, the ultrasonic signal is transmitted from a conventional transducer (1506), while the echo signal is collected by optical resonator-based ultrasonic sensors (1502) in a probe array (1504). A portable optical control module (1508) is used to drive the optical sensors (1502) in the probe array (1504) to detect ultrasonic signals generated by the tissue to be imaged in response to ultrasonic pulses generated by the conventional transducer (1506). The optical control module (1508) is operably coupled to each optical resonator-based ultrasonic sensor (1502) in the probe array (1504). Additionally, the optical control module (1508) is operably coupled to an imaging control and analysis system (1520) configured to drive the conventional transducer (1506), receive signals from the probe array (1504), and reconstruct an ultrasonic image based on the signals received from the probe array (1504).

[0118] Referring again to FIG. 15, the optical control module (1508) includes a light source (1516) and a light receiver (1514) operably coupled to the optical resonator-based ultrasonic sensors (1502) of the probe array (1504). The light source (1516) generates light directed into at least one coupling waveguide (not shown) used to couple light within the optical resonator-based ultrasonic sensors (1502). The light receiver (1514) includes at least one light detector (not shown) configured to detect light received from at least one coupling waveguide, which is modulated by the optical resonator-based ultrasonic sensors (1502). The optical control module (1508) further includes a signal processing module (1512) configured to convert the output of at least one light detector of the light receiver (1514) into an electrical signal encoding the light detector output. The electrical signals generated by the signal processing module (1512) are communicated to the signal outputs (1510) of the probe array (1504) generated in response to the detected ultrasound signals from the tissues to the imaging control and analysis system (1520).

[0119] In various embodiments, the probe array (1504) comprises at least one optical resonator-based ultrasonic sensor (1502). In some embodiments, the probe array (1504) comprises a plurality of optical resonator-based ultrasonic sensors (1502) arranged in an array pattern that includes, but is not limited to, a 1D linear array pattern and a 2D array pattern. The 2D array pattern includes any suitable 2D array pattern without limitation. Non-limiting examples of suitable 2D array patterns include Cartesian lattice patterns, circular patterns such as sensors of a single circle or sensors of multiple concentric circles, and any combination thereof. In one embodiment, the probe array (1504) is a 1D linear array comprising a plurality of sensors (1502), as illustrated in FIG. 15. All sensors of the probe array are encapsulated in a continuous low-exponential polymer layer as described above.

[0120] In various embodiments, the spacing between adjacent sensors (1502) within the sensor array (1504) may be uniform, or the spacing between adjacent sensors (1502) may vary. The spacing between sensors (1502) within the probe array (1504) may be selected based on any one or more of at least several factors, including but not limited to the desired spatial resolution of the imaging system, the dimensions of the WGM resonators and coupled waveguides, the architecture of the sensor array, the avoidance of crosstalk between adjacent sensors, and any other relevant factors without limitation. In some embodiments, the minimum separation between adjacent sensors (1502) within the probe array (1504) is at least 5 μm to avoid crosstalk between the sensors (1502).

[0121] In various additional embodiments, the sensors of the sensor array essentially have the same dimensions. In other embodiments, at least some of the sensors (1502) may have different dimensions. Without being limited to any particular theory, a range of sensor sizes can provide the sensor array with enhanced sensitivity to acoustic signals across various frequency ranges.

[0122] In various additional embodiments, each sensor (1502) of the probe array (1504) is coupled to separate coupling waveguides so that the number of sensors (1502) is equal to the number of coupling waveguides. In other additional embodiments, at least some of the sensors may share coupling to a shared coupling waveguide. In some additional embodiments, the probe array may include one or more shared coupling waveguides shared by additional portions of sensors, as well as by additional portions of sensors each coupled to separate coupling waveguides.

[0123] FIG. 5 is a schematic diagram illustrating the introduction of ultrasonic pulses into tissue and the detection of ultrasonic signals generated by tissue using an optical resonator-based acoustic sensor system (100) within an ultrasonic imaging system (500) similar to the system (1500) illustrated in FIG. 15. Referring to FIG. 5, at least one WGM micro-resonator (102) and a coupled waveguide (104) of the acoustic sensor system (100) may be acoustically coupled to the tissue (504) to be imaged. A conventional ultrasonic transducer (506) directs ultrasonic pulses (508) into the tissue (504) to induce an acoustic signal (502). In one embodiment, light coupled into the WGM micro-resonator (102) is generated using a laser (101) directed through a polarization controller (not shown). Acoustic signals (502) interact with the WGM micro-resonator (102) as described above and are detected in the form of changes in laser signals detected by a photodetector (106) coupled to the output port (108) of the coupled waveguide (104). The output signals of the photodetector (106) are communicated to a computing device (112) that functions as a signal analyzer. In one embodiment, the computing device (122) converts the output signals of the photodetector (106) into acoustic signals in the form of optical resonance amplitudes of the micro-resonator, as shown in FIG. 7. In another embodiment, the computing device (112) converts the output signals of the photodetector (106) into acoustic signals in the form of acoustic signals that can be obtained using the resonance wavelength identified from the spectral response of the micro-resonator (600), as shown in FIG. 6.

[0124] In some embodiments, the ultrasonic imaging system comprises a single optical resonator-based acoustic sensor system. In this embodiment, a focused ultrasonic source is applied to transmit ultrasound, while the single optical resonator-based acoustic sensor system collects echoes and localizes the depths of the reflectors (A-scan image). A B-scan image is obtained by mechanically scanning the boundary source and the sensor.

[0125] In another embodiment, the ultrasonic imaging system comprises an array of optical resonator-based acoustic sensors, as illustrated in FIG. 15. In this embodiment, focusing and scanning of ultrasound are achieved by a transducer phase array. In some embodiments, real-time B-scan images can be acquired by applying a suitable beam-forming algorithm to a group of collected signals from the optical sensors. In another embodiment, oblique plane-wave ultrasound can be transmitted by the transducer phase array and the transmission angle can be scanned. Reflected signals can be collected by an optical resonator-based acoustic sensor array. Ultrafast B-scan image acquisition can be achieved by a suitable beam-forming algorithm.

[0126] In various embodiments, an array of optical resonator-based acoustic sensors comprises at least two WGM resonators arranged in a spatial array, which includes but is not limited to a 2D array such as a linear array, a planar array, or a ring array, and a 3D array such as a cylindrical or hemispherical array. In some embodiments, at least two WGM resonators in the array are each coupled to individual coupling fibers, light sources, and photodetectors. In other embodiments, at least two WGM resonators in the array are coupled to the same coupling fiber, light source, and photodetector.

[0127] In other additional embodiments, at least two WGM resonator-based pressure sensor systems in the array are essentially identical with respect to size, center frequency, operating wavelength, sensitivity, and any other relevant operating parameters. In yet another additional embodiment, at least two WGM resonator-based pressure sensor systems may differ in one or more parameters, including but not limited to resonator diameter, resonator material, gap separation distance, operating wavelength, encasement polymer material, bonding taper material, bonding taper diameter, and any other relevant parameters.

[0128] In a further embodiment, an optical resonator-based acoustic sensor system can be integrated into existing ultrasonic imaging systems to improve the quality of harmonic ultrasonic imaging. Harmonic ultrasonic imaging enjoys high sensitivity and specificity due to high-frequency nonlinear ultrasonic echoes from the imaged target. However, the weak and broadband nature of the nonlinear signal imposes challenging requirements on ultrasonic detectors. An optical resonator-based acoustic sensor can be used to (1) efficiently collect nonlinear ultrasonic echoes; and (2) allow a sufficiently wide detection band to enable pumping ultrasound at higher frequencies and shorter pulse durations (for higher resolution).

[0129] b. Photoacoustic imaging systems

[0130] In various embodiments, optical resonator-based acoustic sensors are integrated into an ultrasonic imaging system. Without being limited to any particular theory, at least one optical pulse is introduced into the tissue to be imaged, and the energy of the incident photons is absorbed by structures within the tissue and re-emitted as photoacoustic signals in the form of ultrasounds. The emitted ultrasounds are subsequently detected by at least one ultrasound transducer, and the detected signals are used to reconstruct photoacoustic images. In various embodiments, optical resonator-based acoustic sensors configured to detect photoacoustic signals are compatible with any existing ultrasonic imaging system without limitation. Non-limiting examples of ultrasonic systems compatible with optical resonator-based acoustic sensors include photoacoustic microscopy (PAM) systems and computed tomography (PACT) systems.

[0131] Referring to FIG. 26, the photoacoustic system (2600) comprises, in one embodiment, a photoacoustic (PA) light source (2602), and the photoacoustic (PA) light source (2602) comprises, but is not limited to, at least one pulse laser configured to generate a plurality of laser pulses (2604) to be directed into a tissue (2606) using at least one optical element of a PA optical module (2608). In one embodiment, each laser pulse (2604) generated by the PA light source (2602) is configured to induce a plurality of PA signals (2610) from structures (2612) within a portion of the tissue (2606) to which the laser pulse (2604) is directed. As described above, the plurality of PA signals (2610) induced by a single laser pulse (2604) are detected by a transducer array (2614) and reconstructed into a PA image (not shown) using any suitable reconstruction method known in the art.

[0132] Referring again to FIG. 26, in one embodiment, PA signals (2610) comprising a plurality of ultrasounds are collected by at least one optical resonator-based ultrasound sensor (2616) in a transducer array (2614). Any suitable optical sensor described herein may be incorporated without limitation as the optical resonator-based ultrasound sensor (2616) in the transducer array (2614). As illustrated in FIG. 26, the photoacoustic system (2600) further comprises at least one transducer light source (2618) and at least one transducer light detector (2620) operably coupled to the optical resonator-based ultrasound sensors (2616) of the transducer array (2614). The light source (2618) generates light directed into at least one coupling waveguide (2622) used to couple the light to the optical resonator-based ultrasound sensors (2616). The transducer photodetector (2620) includes at least one photodetector (not shown) configured to detect light received from at least one coupled waveguide (2622) which is modulated by the WGM resonator (2624) of the optical resonator-based ultrasonic sensor (2616).

[0133] A controller (2626) is used to drive optical sensors (2616) in a transducer array (2614) to detect PA signals (2610) generated by tissue (2606) in response to laser pulses (2604) generated by a PA light source (2602). The controller (2626) is operably coupled to each optical resonator-based ultrasonic sensor (2616) in the transducer array (2614) via transducer light sources (2618) and transducer photodetectors (2620). In some embodiments, the controller may include a signal processing module (not shown) configured to convert the output of at least one transducer photodetector (2620) into electrical signals encoding the detector outputs. Additionally, the controller (2626) is operably coupled to a PA imaging analysis module (2628) configured to reconstruct an ultrasound image based on signals received from the transducer array (2614). In some embodiments, the controller (2626) may be provided in the form of an optical control module similar to the portable driving system shown in FIG. 14 and FIG. 25 and described above.

[0134] In various embodiments, each of at least one pulse laser of the PA light source (2602) may generate multiple laser pulses at a pulse wavelength. The pulse wavelength may be selected based on any one or more of at least some factors, including but not limited to enhanced penetration of a specific tissue to be imaged by the pulse wavelength, enhanced contrast of structures of interest relative to surrounding structures, which may be useful for unlabeled visualization of circulating tumor cells, and enhanced contrast of exogenous structures of interest, which may be useful for SIP-PACT imaging of perfusion of contrast agents such as NIR dyes. In one embodiment, a pulse wavelength in the range of about 650 nm to about 1350 nm may be selected to maximize optical penetration through the entire body of the mammal to be imaged, because this wavelength range is intended to include pulse wavelengths that are less attenuated within mammalian tissues compared to wavelengths outside this "optical window." In one particular embodiment, a pulse wavelength of about 1064 nm may be selected to enable PA imaging in mammalian tissues using a PA imaging system (2600).

[0135] In various embodiments, the PA light source (2602) can generate laser pulses at a single wavelength, at two (double) wavelengths, or at three or more (multiple) wavelengths as needed. In various embodiments, multiple laser pulses can be generated at one or more wavelengths within the range of approximately 650 nm to approximately 1350 nm, thereby enabling maximum optical penetration for whole-body imaging of animal subjects. Without being limited to any particular theory, this wavelength range features enhanced penetration through biological tissues; for example, this wavelength range is previously known to correspond to pulse wavelengths at which mammalian tissues attenuate light minimally.

[0136] In various other embodiments, the PA imaging system (2600) may utilize a single pulse wavelength selected for enhanced penetration of a specific tissue to be imaged, and / or enhanced contrast of structures of interest relative to surrounding structures. In other embodiments, the PA imaging system (2600) may utilize dual and / or multiple pulse wavelengths to enable functional imaging, including but not limited to determining oxygen saturation in blood and other tissues. For example, a first pulse wavelength may be selected to enable maximum contrast for oxy-hemoglobin, and a second pulse wavelength may be selected to enable maximum contrast for deoxy-hemoglobin, or alternatively, to enable maximum contrast for all hemoglobins. Dual / multiple pulse wavelengths may also be selected for enhanced contrast of different structures such as blood cells, CTCs, leukocytes, and contrast agents such as NIR dyes, or enhanced contrast of exogenous structures of interest (i.e., perfusion of contrast agents such as NIR dyes). In various embodiments, the PA imaging system (2600) may include a 720 nm laser such as the LS-2145-LT-150 Ti-Sapphire (Ti-Sa) pulse laser (Symphotic Tii) having a 20 Hz repetition rate and a 12 ns pulse width; a 1064 nm laser such as the DLS9050 pulse laser (Continuum) having a 50 Hz repetition rate and a pulse width in the range of about 5 ns to about 9 ns; and any other suitable pulse laser, but not limited thereto, a pulse laser that generates laser pulses at a single pulse wavelength.

[0137] In various embodiments, the PA optical module (2608) of the PA imaging system (2600) includes one or more optical elements configured to direct a plurality of laser pulses generated by a PA light source (2602) into a tissue (2606) to be imaged. In some embodiments, the focal area of ​​the ultrasound transducer array (2614) corresponds to at least a portion of the tissue to be imaged that is illuminated by the laser pulses (2604), so that PA signals (2610) induced by the plurality of laser pulses (2604) are detected by the transducer array (2614) and used to reconstruct one or more PA images.

[0138] In various embodiments, one or more optical elements (not shown) of the PA optical module (2608) are operably coupled to a PA light source (2602) to receive a plurality of laser pulses generated by at least one pulse laser. Additionally, the one or more optical elements are configured to perform various transformations of a plurality of laser pulses, including but not limited to: changing the direction of travel of each laser pulse; redistributing the distribution of light energy across the cross-sectional area of ​​each laser pulse into an essentially uniform spatial distribution of light energy; changing the cross-sectional size and / or shape of each laser pulse; modulating the light intensity or fluence of each laser pulse; modulating the relative arrival times of two different laser pulses generated by two corresponding pulse lasers; selectively transmitting or blocking the transmission of laser pulses from one or more pulse lasers; and any other suitable transformation of the plurality of laser pulses.

[0139] Non-limiting examples of suitable optical elements suitable for integration within the PA optical module (2608) of the PA imaging system (2600) include prisms, mirrors, diffusers, condensers, lenses, beam splitters, beam combiners, optical fibers, wave guides, and one or more of any other known optical elements suitable for modifying one or more characteristics of a laser pulse. Non-limiting examples of characteristics of a laser pulse that can be modified and / or modulated using one or more optical elements include cross-sectional profiles, cross-sectional dimensions, direction of travel, wave velocity, wavelength, polarization, intensity, phase, wavefront shape, overlap with other laser pulses, cross-sectional energy uniformity, pulse width, delay with respect to other laser pulses in a pulse series, and any other related characteristics of the laser pulse.

[0140] In one embodiment, the diffuser may be configured to homogenize the laser pulse profile so that the energy intensity is uniformly distributed across the cross-sectional area of ​​the laser pulse. Non-limiting examples of suitable diffusers include various engineered diffusers, such as ring diffusers. In one embodiment, the diffuser may be a commercially available engineered diffuser, including but not limited to EDC-10-A-1r (RPC Photonics). Non-limiting examples of suitable capacitors include various custom capacitors, such as custom ring capacitors. Non-limiting examples of suitable prisms include triangular prisms, rhomboidal prisms, and any other suitable prisms. Non-limiting examples of suitable lenses include convex lenses, concave lenses, cylindrical lenses, semi-cylindrical lenses, compound lenses, and any other suitable lenses. In another embodiment, the lens may be a commercially available lens including, but not limited to, an AX-FS-1-140-0 conical lens (Del Mar Photonics). Non-limiting examples of suitable mirrors include planar mirrors, convex mirrors, and concave mirrors.

[0141] In various embodiments, one or more optical elements may be further configured to enable an illumination approach selected according to the area or tissue to be imaged and / or the type of imaging to be performed using the PA imaging system (2600). In one embodiment, one or more optical elements may be configured to enable an upper illumination approach (see FIG. 26) or a lateral illumination approach. The selection of specific optical elements integrated within the PA imaging system (2600) may be at least partially influenced by the illumination approach to be used by the PA imaging system (2600).

[0142] III. Computing Systems and Devices

[0143] FIG. 8 illustrates a simplified block diagram of a computing device (800) for implementing the methods described herein. As illustrated in FIG. 8, the computing device (800) may be configured to implement at least some of the operations associated with the disclosed method using the disclosed optical resonator-based pressure sensor system. The computer system (800) may include a computing device (802). In one embodiment, the computing device (802) is part of a server system (804) which also includes a database server (806). The computing device (802) communicates with a database (808) through the database server (806). The computing device (802) is communicably coupled to the system (810) and the user computing device (830) through a network (850). The network (850) may be any network that enables short-range or wide-range communication between the devices. For example, the network (850) may enable communication combination to the Internet through at least one of many interfaces including, but not limited to, the Internet, LAN (local area network), WAN (wide area network), ISDN (integrated services digital network), dial-up connection, DSL (digital subscriber line), cellular dial-up connection, and cable modem. The user computing device (830) may be any device capable of accessing the Internet, including, but not limited to, a desktop computer, a laptop computer, a PDA (personal digital assistant), a cellular phone, a smartphone, a tablet, a phablet, a wearable electronic device, a smart watch, or other web-based accessible equipment or mobile device.

[0144] In another embodiment, the computing device (802) is configured to perform a plurality of tasks associated with the operation of an imaging system including an optical resonator-based acoustic sensor and / or an optical resonator-based acoustic sensor, including but not limited to the aforementioned ultrasonic (US) and photoacoustic (PA) imaging systems. FIG. 9 illustrates a component configuration (900) of the computing device (902) including a database (910) along with other related computing components. In some embodiments, the computing device (902) is similar to the computing device (802) (illustrated in FIG. 8). A user (904) can access the components of the computing device (902). In some embodiments, the database (910) is similar to the database (808) (illustrated in FIG. 8).

[0145] In one embodiment, the database (910) includes imaging data (918) and algorithm data (912). Suitable imaging data (918) may include medical imaging data, including but not limited to ultrasonic imaging data or photoacoustic imaging data. Suitable algorithm data (912) may include any values ​​of parameters defining the operation of optical WGM resonator-based acoustic sensors, ultrasonic imaging systems, and photoacoustic imaging systems. Suitable algorithm data (912) may include any values ​​of parameters defining algorithms associated with the disclosed method described herein, and / or any image reconstruction algorithms used to reconstruct the aforementioned ultrasonic or photoacoustic images.

[0146] The computing device (902) also includes a number of components that perform specific tasks. In an exemplary embodiment, the computing device (902) includes a data storage device (930), an imaging component (940), an acoustic sensor component (950), and a communication component (960). The data storage device (930) is configured to store data received or generated by the computing device (902), such as any data stored in the database (910) or any outputs of processes implemented by any component of the computing device (902).

[0147] The communication component (960) is configured to enable communication between the computing device (902) and other devices (e.g., the user computing device (830) and system (810) shown in FIG. 8) through multiple network connections using a network such as the network (850) shown in FIG. 8 or predefined network protocols such as TCP / IP (Transmission Control Protocol / Internet Protocol).

[0148] FIG. 10 illustrates the configuration of a remote or user computing device (1002), such as the user computing device (830) shown in FIG. 8. The computing device (1002) may include a processor (1005) for executing instructions. In some embodiments, executable instructions may be stored in a memory region (1010). The processor (1005) may include one or more processing units (e.g., in a multi-core configuration). The memory region (1010) may be any device that enables information, such as executable instructions and / or other data, to be stored and retrieved. The memory region (1010) may include one or more computer-readable media.

[0149] The computing device (1002) may also include at least one media output component (1015) for presenting information to the user (1001). The media output component (1015) may be any component capable of delivering information to the user (1001). In some embodiments, the media output component (1015) may include an output adapter such as a video adapter and / or an audio adapter. The output adapter may be operably coupled to the processor (1005) and may be operably coupled to an output device such as a display device (e.g., a liquid crystal display (LCD), an organic light-emitting diode (OLED) display, a cathode ray tube (CRT), or an "electronic ink" display) or an audio output device (e.g., speakers or headphones). In some embodiments, the media output component (1015) may be configured to present an interactive user interface (e.g., a web browser or a client application) to the user (1001).

[0150] In some embodiments, the computing device (1002) may include an input device (1020) for receiving input from a user (1001). The input device (1020) may include, for example, a keyboard, a pointing device, a mouse, a stylus, a touch-sensitive panel (e.g., a touchpad or a touchscreen), a camera, a gyroscope, an accelerometer, a position detector, and / or an audio input device. A single component, such as a touchscreen, may function as both the output device and the input device (1020) of the media output component (1015).

[0151] The computing device (1002) may also include a communication interface (1025) that can be communicateably coupled to a remote device. The communication interface (1025) may include, for example, a wired or wireless network adapter or a wireless data transceiver for use with a mobile phone network (e.g., GSM (Global System for Mobile communications), 3G, 4G, or Bluetooth) or another mobile data network (e.g., WIMAX (Worldwide Interoperability for Microwave Access)).

[0152] In the memory area (1010), computer-readable instructions are stored for providing a user interface to the user (1001), for example, through a media output component (1015), and optionally for receiving and processing input from an input device (1020). The user interface may include, among other possibilities, a web browser and a client application. Web browsers enable the user (1001) to display and interact with media and other information typically embedded on a web page from a web server or on a website. Client applications enable the user (1001) to interact with a server application associated with, for example, a vendor or business.

[0153] FIG. 11 illustrates an exemplary configuration of a server system (1102). The server system (1102) may include, but is not limited to, a database server (806) and a computing device (802) (both illustrated in FIG. 8). In some embodiments, the server system (1102) is similar to the server system (804) (illustrated in FIG. 8). The server system (1102) may include a processor (1105) for executing instructions. Instructions may be stored, for example, in a memory area (1110). The processor (1105) may include one or more processing units (e.g., in a multi-core configuration).

[0154] The processor (1105) may be operably coupled to a communication interface (1115) so that the server system (1102) can communicate with a remote device, such as a user computing device (830) (illustrated in FIG. 8) or another server system (1102). For example, the communication interface (1115) may receive requests from the user computing device (830) through a network (850) (illustrated in FIG. 8).

[0155] The processor (1105) may also be operablely coupled to the storage device (1110). The storage device (1110) may be any computer operating hardware suitable for storing and / or retrieving data. In some embodiments, the storage device (1110) may be integrated into a server system (1102). For example, the server system (1102) may include one or more hard disk drives as the storage device (1110). In other embodiments, the storage device (1110) may be located outside the server system (1102) and may be accessed by multiple server systems (1102). For example, the storage device (1110) may include multiple storage units, such as hard disks or solid-state disks in a redundant array of inexpensive disks (RAID) configuration. The storage device (1110) may include a storage area network (SAN) and / or network attached storage (NAS) system.

[0156] In some embodiments, the processor (1105) may be operablely coupled to the storage device (1110) through a storage interface (1120). The storage interface (1120) may be any component capable of providing access to the storage device (1110) to the processor (1105). The storage interface (1120) may include, for example, an Advanced Technology Attachment (ATA) adapter, a Serial ATA (SATA) adapter, a Small Computer System Interface (SCSI) adapter, a RAID controller, a SAN adapter, a network adapter, and / or any component providing access to the storage device (1110) to the processor (1105).

[0157] The memory regions (1010 (shown in FIG. 10) and 1110) may include, but are not limited to, RAM (random access memory), such as DRAM (dynamic RAM) or SRAM (static RAM), ROM (read-only memory), EPROM (erasable programmable read-only memory), EEPROM (electrically erasable programmable read-only memory), and NVRAM (non-volatile RAM). The above memory types are merely examples and are therefore not limited to the types of memory available for storing computer programs.

[0158] The computer systems and computer implementation methods discussed herein may include additional, fewer, or alternative actions and / or functionalities, including those discussed elsewhere in this specification. Computer systems may include or be implemented through computer-executable instructions stored on non-transient computer-readable media. Methods may be implemented through one or more local or remote processors, transceivers, servers, and / or sensors (e.g., processors, transceivers, servers, and / or sensors mounted on vehicles or mobile devices, or associated with smart infrastructure or remote servers), and / or through non-transient computer-readable media or computer-executable instructions stored on such media.

[0159] As recognized based on the foregoing specification, the foregoing aspects of the disclosure may be implemented using computer programming or engineering techniques comprising computer software, firmware, hardware, or any combination or subset thereof. Any such resulting program having computer-readable code means may be implemented or provided in one or more computer-readable media, thereby enabling the manufacture of computer program products, i.e., articles of manufacture, according to the aspects discussed in the disclosure. Computer-readable media may be, for example, fixed (hard) drives, diskettes, optical discs, magnetic tapes, semiconductor memory such as read-only memory (ROM), and / or any transmission / reception media such as the Internet or other communication networks or links, but are not limited thereto. Articles of manufacture containing computer code may be manufactured and / or utilized by executing code directly from one medium, by copying code from one medium to another, or by transmitting code over a network.

[0160] These computer programs (also known as programs, software, software applications, “apps,” or code) contain machine instructions for a programmable processor and may be implemented in high-level procedural and / or object-oriented programming languages ​​and / or assembly / machine languages. As used herein, the terms “machine-readable medium” and “computer-readable medium” refer to any computer program product, device, and / or device (e.g., magnetic disks, optical disks, memory, programmable logic devices (PLDs)) used to provide machine instructions and / or data to a programmable processor comprising a machine-readable medium that receives machine instructions as machine-readable signals. However, “machine-readable medium” and “computer-readable medium” do not include transient signals. The term “machine-readable signal” refers to any signal used to provide machine instructions and / or data to a programmable processor.

[0161] As used herein, a processor may include any programmable system comprising microcontrollers, RISC (reduced instruction set circuits), ASIC (application specific integrated circuits), logic circuits, and any other circuit or processor capable of executing the functions described herein. The above examples are merely examples and are therefore not intended to limit the definition and / or meaning of the term “processor” in any way.

[0162] As used herein, the terms “software” and “firmware” are interchangeable and include any computer program stored in memory for execution by a processor, including RAM memory, ROM memory, EPROM memory, EEPROM memory, and non-volatile RAM (NVRAM) memory. The above memory types are merely examples and are therefore not limited to the types of memory available for storing computer programs.

[0163] In one embodiment, a computer program is provided, and the program is implemented on a computer-readable medium. In one embodiment, the system runs on a single computer system without requiring access to a server computer. In an additional embodiment, the system runs in a Windows® environment (Windows is a registered trademark of Microsoft Corporation, Redmond, Washington). In another embodiment, the system runs in a mainframe environment and a UNIX® server environment (UNIX is a registered trademark of X / Open Company Limited, Reading, Berkshire, UK). The application is designed to run in various different environments flexibly and without compromising any key functionality.

[0164] In some embodiments, the system comprises a plurality of components distributed among a plurality of computing devices. One or more components may be in the form of computer-executable instructions implemented on a computer-readable medium. Systems and processes are not limited to the specific embodiments described herein. Additionally, components of each system and each process may be implemented independently and separately from other components and processes described herein. Each component and process may also be used in combination with other assembly packages and processes. These embodiments may enhance the functionality and capabilities of computers and / or computer systems.

[0165] The definitions and methods described herein are provided to better define the present disclosure and to guide those skilled in the art in practicing the present disclosure. Unless otherwise stated, terms should be understood according to the ordinary use by those skilled in the art.

[0166] In some embodiments, numerical values ​​expressing the amount, characteristics, such as molecular weight, reaction conditions, etc. of a component used to describe and claim specific embodiments of this disclosure should be understood as being modified by the term “about” in some cases. In some embodiments, the term “about” is used to indicate that the value includes the standard deviation of the mean for the device or method used to determine the value. In some embodiments, the numerical parameters disclosed in the description and appended claims are approximations that may vary depending on the desired characteristics to be obtained by a particular embodiment. In some embodiments, numerical parameters should be interpreted in light of the number of reported significant figures and by applying conventional rounding techniques. Although the numerical ranges and parameters describing a broad range of some embodiments of this disclosure are approximations, the numerical values ​​described in specific examples are reported as accurately as possible. The numerical values ​​presented in some embodiments of this disclosure may include specific errors resulting from the standard deviation found in each of their respective test measurements. References to ranges of values ​​in this specification are intended merely to serve as a method of abbreviating each individual value within the range. Unless otherwise indicated in this specification, each individual value is included in the specification as if it were individually mentioned in this specification. References to discrete values ​​are understood to include ranges between each value.

[0167] In some embodiments, singular terms (“a,” “an,” and “the”) and similar references used in the context of describing specific embodiments (particularly in the context of specific claims among the following claims) may be interpreted to cover both singular and plural forms unless specifically stated otherwise. In some embodiments, the term “or” as used herein, including in the claims, is used to mean “and / or” unless explicitly indicated to refer only to alternatives or the alternatives are mutually exclusive.

[0168] The terms "comprise," "have," and "include" are open-form linking verbs. Any one or more of these verbs, such as "comprises," "comprising," "has," "having," "includes," and "including," are also open-form. For example, any method that "comprises," "has," or "includes" one or more steps is not limited to possessing only such one or more steps and may also cover other unlisted steps. Similarly, any composition or device that "comprises," "has," or "includes" one or more features is not limited to possessing only such one or more features and may also cover other unlisted features.

[0169] All methods described herein may be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by the context. Any and all examples provided in connection with specific embodiments of this specification, or the use of exemplary language (e.g., “such as”), are merely intended to better illustrate this disclosure and do not impose any limitation on the scope of this disclosure as otherwise claimed. No language in this specification should be interpreted as representing any non-claimed element essential to the practice of this disclosure.

[0170] The groupings of alternative elements or embodiments of the disclosure disclosed herein shall not be interpreted as limitations. Each group member may be referenced and claimed individually or in any combination with other members or elements of the group found herein. One or more members of a group may be included in or removed from a group for reasons of convenience or patentability. Where any such inclusion or removal occurs, the specification shall be deemed to include the modified group herein and thus satisfy the described description of all Markush groups used in the appended claims.

[0171] Any publications, patents, patent applications, and other references cited in this application are incorporated herein by reference in their entirety for all purposes, to the same extent that each individual publication, patent, patent application, or other reference is specifically and individually indicated as being incorporated by reference in its entirety for all purposes. The citation of references in this specification shall not be construed as an acknowledgment that such references are prior art to the present disclosure.

[0172] Although the present disclosure has been described in detail, it will be apparent that modifications, variations, and equivalent embodiments are possible without departing from the scope of the present disclosure as defined in the appended claims. It should also be understood that all examples in the present disclosure are provided as non-limiting examples.

Claims

Claim 1 Acoustic sensor comprising: an optical whispering gallery mode resonator; a coupling waveguide for optically coupling to the resonator—the coupling waveguide being spaced apart from the resonator by a separation gap—; and a polymer enclosing a portion of the coupling waveguide and the resonator—the polymer having dimensions engineered to enhance acoustic focusing on the optical whispering gallery mode resonator—; wherein each of the resonator and the coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer, and the dimensions engineered to enhance acoustic focusing are the upper boundary of the polymer, which is a convex upper boundary. Claim 2 In claim 1, the separation gap is selected so that the acoustic sensor operates at an operating condition selected from the critical coupling of the resonator and the coupled waveguide or at a maximum load factor. Claim 3 An acoustic sensor according to claim 1, wherein the resonator comprises a diameter in the range of 50 μm to 200 μm. Claim 4 An acoustic sensor according to claim 1, wherein the separation gap includes a gap distance in the range of 0.6 μm to 0.8 μm. Claim 5 In claim 1, the separation gap causes a maximum load factor during the operation of the acoustic sensor, an acoustic sensor. Claim 6 An acoustic sensor according to claim 1, wherein the coupling waveguide is a tapered optical fiber having a minimum taper diameter of less than 1.5 μm. Claim 7 In claim 1, the acoustic sensor encodes pressure fluctuations as fluctuations in the transmission amplitude through the resonator. Claim 8 An acoustic sensor according to claim 1, wherein the polymer is a UV-curable polymer having a refractive index of 1.

33. Claim 9 An acoustic sensing system comprising: an optical whispering gallery mode resonator; a coupling waveguide for optically coupling to the resonator—the coupling waveguide having a first end and a second end opposite to the first end, and the coupling waveguide being spaced apart from the resonator by a separation gap—; a polymer enclosing portions of the resonator and the coupling waveguide—the polymer having dimensions engineered to enhance acoustic focusing on the optical whispering gallery mode resonator—; a light source coupled to the first end of the coupling waveguide protruding from the polymer; and a photodetector coupled to the second end of the coupling waveguide and protruding from the polymer; wherein each of the resonator and the coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer, and the dimensions engineered to enhance acoustic focusing are the upper boundary of the polymer, which is a convex upper boundary. Claim 10 An acoustic sensing system according to claim 9, further comprising a driving system having a computing device having a processor, wherein the driving system is operably coupled to the light source and the photodetector, and the driving system is configured to acquire a transmission spectrum by operating the light source in a range of wavelengths and receiving a plurality of detector signals from the photodetector—the detector signals encode the transmission of light from the light source through a coupled waveguide coupled to the resonator—; select an operating wavelength for detecting pressure fluctuations based on the transmission spectrum; select the separation gap based on at least one transmission spectrum; and detect pressure fluctuations by operating the light source in the operating wavelength and receiving a second plurality of signals from the photodetector. Claim 11 In paragraph 10, the acoustic sensing system encodes pressure fluctuations as fluctuations in a transmission amplitude wave optical whispering gallery mode resonator. Claim 12 An ultrasonic imaging device comprising: an acoustic sensor, wherein the acoustic sensor comprises: an optical whispering gallery mode resonator; a coupling waveguide for optically coupling to the resonator—the coupling waveguide having a first end and a second end opposite to the first end, and the coupling waveguide being spaced apart from the resonator by a separation gap—; a polymer encapsulating portions of the resonator and the coupling waveguide—the polymer having dimensions engineered to enhance acoustic focusing on the optical whispering gallery mode resonator—; a light source coupled to the first end of the coupling waveguide protruding from the polymer; and a photodetector coupled to the second end of the coupling waveguide opposite to the first end and protruding from the polymer; wherein each of the resonator and the coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer, and the dimensions engineered to enhance acoustic focusing are the upper boundary of the polymer, which is a convex upper boundary. Claim 13 In paragraph 12, the acoustic sensor is an ultrasonic imaging device that encodes pressure fluctuations as fluctuations in the transmission amplitude through the resonator. Claim 14 In claim 12, the ultrasonic imaging device is configured such that the acoustic sensor detects ultrasonic pulses generated within the region of interest in response to excitatory ultrasonic pulses directed into the region of interest by an ultrasonic transducer. Claim 15 A photoacoustic imaging device comprising an acoustic sensor, wherein the acoustic sensor comprises: an optical whispering gallery mode resonator; a coupling waveguide for optically coupling to the resonator—the coupling waveguide having a first end and a second end opposite to the first end, and the coupling waveguide being spaced apart from the resonator by a separation gap—; a polymer encapsulating a portion of the resonator and the coupling waveguide—the polymer having dimensions engineered to enhance acoustic focusing on the optical whispering gallery mode resonator—; a transducer light source coupled to the first end of the coupling waveguide protruding from the polymer; and a transducer photodetector coupled to the second end of the coupling waveguide opposite to the first end and protruding from the polymer. A photoacoustic imaging device comprising a photoacoustic light source; wherein each of the resonator and the coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer, and the dimensions engineered to enhance acoustic focusing are the upper boundary of the polymer, which is a convex upper boundary. Claim 16 In paragraph 15, the acoustic sensor is a photoacoustic imaging device that encodes pressure fluctuations as fluctuations in the transmission amplitude through the resonator. Claim 17 In claim 15, the photoacoustic imaging device is configured such that the acoustic sensor detects photoacoustic signals generated within a region of interest in response to illumination by laser pulses generated by the photoacoustic light source. Claim 18 A method for detecting ultrasonic waves, comprising the step of providing an acoustic sensing system—the acoustic sensing system comprises: an optical whispering gallery mode resonator; a coupling waveguide for optically coupling to the resonator—the coupling waveguide having a first end and a second end opposite to the first end, and the coupling waveguide being spaced apart from the resonator by a separation gap—; a polymer encapsulating a portion of the resonator and the coupling waveguide—the polymer further forms a sample contact surface, and the polymer has dimensions engineered to enhance acoustic focusing on the optical whispering gallery mode resonator—; a light source for coupling to the first end of the coupling waveguide protruding from the polymer; and a photodetector coupled to the second end of the coupling waveguide and protruding from the polymer; Each of the above resonator and the above coupling waveguide has a refractive index higher than the corresponding refractive index of the polymer, and the dimensions engineered to enhance the acoustic focusing are the upper boundary of the polymer, which is a convex upper boundary; the step of acoustically coupling the sample contact surface with the sample so that ultrasonic waves emitted from within the sample are conducted through the polymer to a portion of the resonator and the above coupling waveguide; the step of introducing light generated by the light source to the first end of the above coupling waveguide; the step of converting light from the second end of the above coupling waveguide detected by the light detector into detector signals encoding the amplitude of the detected light; and the step of converting the detector signals into pressure using a predetermined calibration rule.

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