RELATED APPLICATION(S)

This application claims the benefit of U.S. Provisional Application No. 61/443,925, filed on February 17, 2011.

The entire teachings of the above application are incorporated herein by reference.

BACKGROUND OF THE INVENTION

Most ultrasound detection systems are based on piezoelectric, electromagnetic or capacitive effects. Typically, they have inherent difficulty in achieving broad bandwidth, high frequency, miniaturization and safety. Optical ultrasound technology has been applied to provide simplified structure, reduced size improved biocompatibility and higher frequency. Several optical ultrasound technologies have been proposed. However, most such proposals operate under a simplex scheme whereby ultrasound is generated, or detected, but not both. Further, most parameters of such probes, such as signal-to-noise ratio, resolution, penetration depth, focus point, and direction, are preset during fabrication.

Therefore, a need exists for a probe that minimizes or overcomes the above mentioned problems.

SUMMARY OF THE INVENTION

The present invention generally relates to a photoacoustic probe that both generates ultrasonic waves by modulated optical radiation and detects reflections of that ultrasonic radiation by a Fabry-Perot (FP) cavity component within the probe.

In one embodiment, a photoacoustic probe of the invention includes an optical fiber, a diaphragm at the optical fiber whereby the optical fiber and the diaphragm define a cavity, and an energy absorption film at the optical fiber. An activating laser directed through the optical fiber can excite the energy absorption film to thereby generate an acoustic wave that, upon reflection from a remote surface, can deflect the diaphragm and modify reflection of a detecting laser that is also directed through the optical fiber. In another embodiment, the invention is a method of detecting an acoustic wave, including the steps of directing an activating laser through an optical fiber to an energy absorption film at the optical fiber to thereby generate an acoustic wave, and directing a detecting laser through the optical fiber and a cavity to a diaphragm at the optical fiber, the cavity being defined by the optical fiber and the diaphragm. An interference pattern generated at least in part by reflection of the detecting laser from a surface of the diaphragm is measured and is indicative of the reflection of the acoustic wave from a remote surface.

This invention has many advantages. For example, the photo acoustic probe of the invention can be employed as a replacement for traditional ultrasonic probes employed in echography, such as is employed to conduct spectral analysis of in-vivo tissues, coronary arteries, skin tumors and the prostate glands. Further, probes can be employed in diagnosing misplacement of stents during coronary intravascular ultrasound procedures and, because the probes can be of very small size, they can be employed where limited space is available to thereby provide autonomous intelligence generally not provided by robotics/bio-mimic systems or surveillance systems of unmanned miniature vehicles. Further, the photoacoustic probe of the invention can be employed in environments that are chemically or electrically hazardous or in high temperature conditions during, for example, real-time structural health monitoring and material characterization. Further, the photoacoustic probe of the invention can be employed in strong magnetic or electrical environments, such as magnetic resonance imaging (MRI) machines, where electrical counterparts are not compatible.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be apparent from the following more particular description of example embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments of the present invention.

FIGs. 1A and IB are cross-sectional end and views, respectively, of one embodiment of a photoacoustic probe of the invention.

FIGs. 2A and 2B are cross-sectional and end views, respectively, of another

embodiment of the photoacoustic probe of the invention.

FIGs. 3A and 3B are cross-sectional and end views, respectively, of still another embodiment of the photoacoustic probe of the invention.

FIGs. 4A and 4B are cross-sectional and end views, respectively, of still another embodiment of the photoacoustic probe of the invention.

FIGs. 5 A and 5B are cross-sectional and end views, respectively, of still yet another embodiment of the photoacoustic probe of the invention.

FIGs. 6A and 6B are cross-sectional and end views, respectively, of another

embodiment of the photoacoustic probe of the invention.

FIG. 7 is a perspective view of one embodiment of an energy absorbing layer of one embodiment of photoacoustic probe of the invention.

FIGs. 8A through 8C are schematic views of one embodiment of a system of the invention (Fig. 8A) and of ultrasound waves focused on a target (Fig. 8B) and steered in a different direction (Fig. 8C).

FIG. 9 is a schematic representation of a photoacoustic probe of the invention in a blood vessel of a mammal.

Fig. 10 is a schematic representation of an apparatus employed to demonstrate one embodiment of the invention.

Fig. 11 is a plot of acoustic signals generated by a gold nanocomposite employed by the apparatus represented in Fig. 10.

Fig. 12 are plots of acoustic signals generated by the apparatus of Fig. 10. DETAILED DESCRIPTION OF THE INVENTION

The present invention generally is directed to an optical fiber tip that integrates an all- optical ultrasonic generator module and receiver module. The optical fiber tip, as a

photoacoustic probe, employs a phased-array technique to control directionality and focus of ultrasonic waves toward a target.

Photoacoustics are employed to generate ultrasonic waves by modulated optical radiation. In an "unconfined" approach, laser energy is exerted directly onto a target to generate ultrasound. Examples of suitable targets include composites, liquids, silicon and biological tissues. One possible limitation of such techniques is thermal damage to the target. In an alternative, "confined" approach, a thin absorbing film, such as a thermoelastic material, is employed to absorb optical radiation and thereby generate ultrasonic waves that propagate toward the target. The invention employs the confined approach.

One embodiment of a photoacoustic transducer of the invention is represented in Fig. 1A. As shown therein, photoacoustic transducer 10 includes multimode fiber 12. Multimode fiber 12 includes core 14 and cladding 16. An example of a suitable cladding material includes silicon dioxide. Core 14 of multimode fiber 12 typically are formed of the same material, but core 14 is doped with a suitable dopant, such as gemanium (Ge). Alternatively, the cladding is doped with fluorine (F) and the core is essentially pure silicon dioxide. The diameter of multimode fiber 12 of photoacoustic transducer 10 typically is in a range of between about 125 μιη and about 800 μιη. Typically, the diameter of core 14 of multimode fiber 12 is in a range of between about 50 μιη and about 600 μιη. However, the size of both fibers can be further tapered down to micrometer size; or bigger sizes of the fibers can be used if necessary. The thickness (t) of multimode fiber 12 typically is in a range of about between 30 μιη and about 200 μιη. Multimode fiber 12 includes first planar surface 18, which typically is orthogonal to a major longitudinal axis of photoacoustic transducer 10.

Diaphragm 20 is bonded to first surface 18. Diaphragm 20 is typically formed of silicon dioxide, silicon nitride or a polymer, such as polydimethylsiloxane (PDMS), epoxy, or polymethylmethacrylate (PMMA). In one embodiment, diaphragm 20 is fabricated by growing an oxide layer on a silicon wafer, followed by etching away a silicon wafer. A silicon substrate is used to grow an oxide layer. Certain thickness of the silicon dioxide layer can be controlled precisely by monitoring the growing time. The silicon dioxide diaphragm is released by back etching away the silicon through wet etching or dry etching methods. The wet etching involves potassium hydroxide (KOH) solution and the dry etching involves deep reactive-ion etching (RIE).

A diaphragm of silicon nitride can be fabricated in a similar manner, wherein a nitride layer is grown on a surface of a silicon wafer, followed by etching away the silicon wafer.

Generally, diaphragm 20 has a thickness in a range of between about 0.5 μιη and about 30 μιη or between about 1 um and about 10 um. Further, diaphragm 20 is bonded to first surface 18 by a suitable method, such as thermally bonding using laser or torch.

Diaphragm 20 can be bonded to surface 18 of multimodal fiber 12 by a suitable technique, such as thermal bonding, laser bonding or chemical synthesis, as is known in the arts. For example, thermal bonding is conducted by heating diaphragm 20 and multimodal fiber 12 until they are both partially melted and then bonded together. Laser bonding can be conducted by locally heating the diaphragm and the fiber to bond them together. Chemical synthesis generally is employed to bond a polymer diaphragm, which can be synthesized directly over recessed portion 22.

Fabry-Perot cavity 22 is defined by recessed portion 21 of core 16 and diaphragm 20. Typically, depth (d) of Fabry-Perot cavity 22 is in a range of between about 5 μιη and about 100 μιη and has a width (w) in a range of between about 10 μιη and about 600 μιη.

Diaphragm 20 includes surface 24. Energy absorption film 26 is bonded to surface 24 of diaphragm 20. Energy absorption film 26 can be any suitable energy absorption film known to convert optical radiation to ultrasonic radiation. As can be seen in Fig. IB, energy absorption film defines opening 28 at diaphragm 20. Typically, energy absorption film 26 has a thickness in a range of between about 0.5 μιη and about 800 μιη.

An example of a suitable material of energy absorption film 26 includes graphite mixed within curable polymers such as PDMS or epoxy, or some other suitable material having a relatively high coefficient of thermal expansion (CTE), a relatively high optical absorption coefficient and high temperature survivability. In one embodiment of the present invention, gold nanoparticles are combined with graphite or gold nanoparticles alone mixing within curable polymers such as PDMS or epoxy to form an absorbing film of a photoacoustic probe. In a specific embodiment, the gold nanoparticles include gold nanorods, preferably having an aspect ratio in a range between about 1.0 and about 6.5 and, optimally, an effective radius in a range of from about 8 nm to about 25 nm. Alternatively, gold nanospheres, having a diameter in the range of between about 10 nanometers to about 100 nanometers, are employed. In still another embodiment, the nanoparticles can be in the form of nanoshells having a total radius, for example, in a range from about 50nm to about 150nm, and a core/shell ratio in a range of from about 0.1 : 1 to about 1 : 1.

Multimode fiber 12 generally is formed by bonding a multimode fiber to single mode fiber 28 by a suitable technique, such as fusion splicing.

In another embodiment of the invention, shown in Figs. 2A and 2B, diaphragm 34 is recessed within Fabry-Perot cavity 22. Diaphragm 34 is bonded to core 14 of multimode fiber 12 by the same method as that employed to fabricate the embodiment shown in Figs. 1A and IB.

In still another embodiment, as shown in Figs. 3A and 3B, second surface 36 is raised from first surface 18. Diaphragm 38 is bonded to second surface 36.

In yet another embodiment, shown in Figs. 4A and 4B, trench 40 partitions energy absorption film 26 from portion 42 of diaphragm 44 that, in combination with recessed portion 46 of core 14 of multimode fiber 14, defines Fabry-Perot cavity 22. Trench 40 can be formed employing the same technique as that employed to form recessed portion 46. For example, trench 40 can be formed by wet etching with 49% hydrofluoric acid (HF). Alternatively, trench 40 can be fabricated by use of a focused ion beam (FIB).

Suitable trenches may have a width in a range of between about 1 micrometer and about 120 micrometers. In one example, trench 40 may have a width in a range of between about 1 micrometer and about 10 micrometers. Trench 40 may have a depth in a range of between about 1 micrometer and about 30 micrometers. In one example, trench 40 may have a depth in a range from about 1 to about 20 micrometers.

Trench 40 is employed to minimize cross-talk between acoustic waves generated by energy absorption film and reflected waves that are detected by deflection of diaphragm 44. In one embodiment, for example, the photoacoustic transducer of the invention can be fabricated from an optical fiber having a diameter of about 125 micrometers. Generally speaking, the diameter of the photoacoustic transducer is much smaller than the wavelength of ultrasonic waves (e.g., about 1.5 millimeters for about 1 MHz). If diaphragm 44 has a diameter of about 5 micrometers and a thickness of 0.3 micrometers, the resonant frequency is 80MHz and the sensitivity is 0.01 nm/kPa. In one embodiment, cantilever having a length of about 112 micrometers, a width of about 14 micrometers and a thickness of 3.7 micrometers have been fabricated that are anchored to a fiber having a diameter of 125 micrometers. In an alternate embodiment, FIB has been employed to mill a trench in the form of a ring 80 micrometers in diameter, 3 micrometers in width and about 4.5 micrometers in depth. Another embodiment, shown in Figs. 5 A and 5B, include energy absorption film 48 covering diaphragm 24 at Fabry- Perot cavity 22. Alternatively, energy absorption film 48 might only partially cover diaphragm 24 at Fabry-Perot cavity 56.

In still another embodiment, shown in Figs. 6A and 6B, multimode fiber 12 is replaced by tubing 54 which, together with single mode fiber 28 and diaphragm 20, define Fabry-Perot cavity 56.

As an alternative to gold nanorods, other nanoparticles, including silver, aluminum, and gold-coated carbon tubes can be employed. Gold nanoparticles can be formed by a suitable method, such as a sodium citrate reduction method, as is known in the art. Examples of suitable methods are described in Enustun, B.V. and J. Turkevich, Coagulation of Colloidal Gold, Journal of the American Chemical Society, 1963. 85(21): p. 3317-3328, and Vakarelski, I. U., Maenosono, R., Kwek, J. W., and Higashitani, K., Thermal modification of layer-by- layer assembled gold nanoparticle films, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 340 (1-3), 193-198 (2009) the teachings of which are included herein by reference in their entirety. Following fabrication of the nanoparticles, the energy absorption layer can be formed by depositing the nanoparticles by a layer-by-layer technique, as is known in the art, and as described, for example, in Vakarelski, I. U., Maenosono, R., Kwek, J. W., and Higashitani, K., "Thermal modification of layer-by-layer assembled gold nanoparticle films," Colloids and Surfaces A: Physicochemical and Engineering Aspects, 340 (1-3), 193-198 (2009) the teachings of which are incorporated herein by reference in their entirety. The energy absorption layer can include, for example, between about 1 and about 1 ,000 bilayers of gold particles. In one embodiment, the energy absorption layer has a thickness in a range of between about 20 micrometers and about 40 micrometers.

Alternatively, the energy absorption film can be fabricated by a nano-imprint technique, wherein a checkerboard-like nanostructure is fabricated to enhance photoacoustic generation efficiency, as shown in Fig. 7. In one embodiment of the nano-imprint technique, a nanostructure includes a combination of gold cells 60 and polymer cells 62, such as polymer cells of polydimethylsiloxane (PDMS). In one embodiment of this method, a PDMS layer is freshly deposited on a surface of a multimodal fiber. A mold is employed to fabricate a pattern of gold cells on a surface. The gold layer is then deposited on top of the PDMS layer. The deposition of gold and PDMS is performed alternately. The dimension of the gold cells can be controlled to a range of between about 10 nanometers and about 100 nanometers. Because different sizes of gold cells correspond to different maximum absorption wavelengths, a phased array technique, such as is known in the art, can be employed. One aspect of the invention includes exciting different wavelengths of laser onto different dimensions of gold cells.

In another embodiment, the same gold nanostructure shown in Fig. 7 can be fabricated by an FIB technique, wherein the sequence of the deposition of gold and PDMS is reversed. Generally speaking, the gold layer is deposited on a surface of the multimodal fiber first, and FIB is introduced to generate a pattern. Thereafter, a PDMS layer is coated on the gold pattern. On the PDMS layer the FIB is introduced again to fabricate the PDMS pattern. The FIB etching and the deposition are performed alternately. The dimensions of the gold cell and the PDMS cell can be controlled very precisely by the FIB.

In still another embodiment, an energy absorbing layer can be formed by exciting a glass with a femtosecond laser to thereby result in a nanospike having a diameter of about 20 nm. After the glass is excited with the femtosecond laser, the whole glass substrate is coated with a gold layer of about 20 nm in thickness. The consequent gold nanostructure can be employed to generate an acoustic wave by application of the photoacoustic principle, as embodied by the invention. Examples of suitable structures are described in "Surface-enhanced Raman scattering on optical material fabricated by femtosecond laser," Wenhui Wang, Haibin Huo, Nan Wu, Mengyan Shen, Charles Guthy, and Xingwei Wang, Proc. SPIE 7673, 76730K (2010), DOI: 10.1117/12.852617 and "Surface Enhanced Raman Scattering Sensing with Nanostructures Fabricated by Soft Nanolithography," Haibin Huo, Cong Wang, Haizhou Ren, Michael Johnson, Mengyan Shen Journal of Macromolecular Science, Part A Vol. 46, Issue. 12, 2009, the teachings of both of which are incorporated herein by reference in their entirety. Alternatively, the energy absorption layer can be formed by depositing a thin layer of tin on a glass surface, which is then anodized. A gold layer is then deposited on the resulting porous structure to form another embodiment of the energy absorbing layer.

In yet another embodiment, energy absorption layer includes a nanocomposite of a polymer mixed with gold nanoparticles. The gold nanoparticles can be formed either before mixing with the polymer or after mixing gold with the polymer. In one embodiment the polymer is PDMS, which features a relatively high co-efficient of thermal expansion and thus absorb laser light at a corresponding maximum absorption wavelength. In one embodiment of a system for generating ultrasonic waves, an interfering pattern can be directed toward a remote target. As shown in Fig. 8A, system 70 includes photoacoustic probe 72 linked to circulator 74, which is employed to isolate the reflection laser from the input laser. System 70 also includes filter, photodetector (PD) 76, phase control module 77, actuation laser 78, detection laser 80, and wavelength multiplexer 82. In one embodiment, the activity laser and the detecting laser are multiplexed, such as by a time division multiplexing (TDM) scheme. Photoacoustic probe 72 includes distinct energy absorption films 84, 86. In use, phased array and wavelength division multiplexing schemes are employed to steer the direction of the ultrasound generated at energy absorption films 84, 86. The optical absorption peaks of energy absorption films 84, 86 specifically correspond to optical wavelengths from actuation lasers wavelengths 88, 90. Energy absorption films 84, 86 can be independently triggered by lasers with specific wavelengths. The time delay between each trigger and the spatial arrangement of energy absorption films 84, 86 can be employed to form predictable interference patterns, which can be steered in any desired direction, such as is shown in Figs. 8B and 8C. The signal angle of the interference pattern can be much narrower then that generated from a single source. The ultrasound frequency generated by energy absorption films 84, 86 can be optimized by using adjunctive gain, depth, and focal length controls. Amplitude and phase distributions are capable of producing desired multiple focus field patterns to provide precise control over the intensity and power level of each control point, as well as to provide a weighted solution to increase the excitation efficiency that will enhance the total power delivery of the probe.

Multimode fiber 12 of photoacoustic transducer is connected at core 32 of single mode fiber 28 to a light source 82, light source 82 provides at least two lasers. One laser is pulsed and has a pulse width in a range of between about 1 nanosecond and about several hundred nanoseconds. In one embodiment, the wavelengths of the activating lasers are in a range of between about 500 nm and about 1200 nm. In a specific embodiment, one of the activating lasers has a wavelength of about 527 nm and another activating laser has a wavelength of about 1067 nm. The first pulsed laser is tuned at a maximum absorption wave length of energy absorption film 84, to provide an acoustic signal at energy absorption film 84 that is reflected off a remote object and back to diaphragm R, the consequence deflection of which is detected by changes in the second laser provided by source 82. The second detection laser is tuned in C-band in order to interrogate deflection of diaphragm R, preferably at the lowest possible loss of transmission signal. Optimally, a second pulsed laser with a different wavelength can be employed to provide an acoustic signal at energy absorption film 86. The pulsed lasers do not interfere with each other because their wavelengths are different. The energy absorption films of one embodiment of the invention have different optical absorption peaks that correspond to different optical wavelengths of the activating lasers. In an embodiment of the invention, the energy absorption films are arranged in an array at the optical fiber and the activating lasers independently excite corresponding energy absorption films to form an acoustic wave interference pattern and thereby direct the generated acoustic wave.

In one embodiment, two lasers are employed, namely a 527nm Nd:YLF nanosecond laser [Quantronix Falcon 527-30-M] and a 1064 nanometer Nd:YVO nano second laser

[Quantronix Lsprey-1064-20-L] can be employed for acoustic generation and a tunable diode laser (new focus TLB-6600) with a wavelength range between 1520 and 1570 nanometers for detection can be employed. Alternatively, the wavelength range can be from about 1260 nm to about 1360 nm. A deflection of the diaphragm caused by an ultrasound echo can be calculated by monitoring the Fabry-Perot interference spectrum. In addition, by tuning the wavelength of the detection laser 80 to the quadrature point, which is a point in the reflection interference pattern. The quadrature point is used to help fix the wavelength of the laser so that the interference pattern shift caused by the pressure can be converted into the intensity change. A deflection of the reception element can be obtained by the amplified photo detector. Filter 92 can be used in front of the photo detector to unsure that only the echo signal from the receiver, not the light from the generation lasers, is detected.

In one embodiment, a photoacoustic probe 94 of the invention can be inserted through catheter 96 into blood vessel 98 of a mammal, and the ultrasonic wavelength of the energy absorption layer can be directed toward a wall of the blood vessel where ultrasonic reflecting of a stenosed area 100 can be detected by the photoacoustic probe, as shown in Figure 9.

An example of one embodiment of the invention follows. EXEMPLIFICATION

Introduction

The motivation of the work was to develop a fiber optic ultrasound transducer which generates ultrasound through optical approach (photoacoustic generation). However, a major drawback of photoacoustic generation is low generation efficiency. In order to enhance the efficiency, novel photoacoustic generation materials were developed featuring a high optical energy absorption capability and a high coefficient of thermal expansion (CTE). Such material would be improved in both factors in order to enhance the photoacoustic generation efficiency.

For high optical energy absorption capability, we used gold nanoparticles (Au NPs) because they exhibit high optical radiation energy absorption capabilities at their plasmon resonance frequencies. For high CTE, we used PDMS. We synthesized Au NPs within PDMS directly so that the high optical energy absorption capability and high CTE can be combined together. We called this material the gold nanocomposite. We also tried graphite mixing within PDMS but the generation efficiency was not as high as the one from the gold nanocomposite.

After the gold nanocomposite was synthesized, the material was coated on the tip of an optical fiber for the photoacoustic generation.

Method and Materials

In one specific embodiment, a gold nanocomposite was formed by preparing polydimethylsiloxane (PDMS) by mixing a suitable base and a suitable curing agent, such as are known in the art, in a 10:3 weight ratio. About 30 mg of HAu Cl ₄ salt was finely crushed by a glass rod. About 0.8 grams of the PDMS were mixed with the 30 mg of gold salt. The PDMS mixture was placed in an ultrasonic bath of ice water for about thirty minutes. The PDMS mixture was degassed for about thirty minutes and then coated on a glass slide. The glass slide was coated with the PDMS mixture and baked for about four hours at 70°C. Experimental setup

PA generation verification experiments were performed in order to evaluate the efficiency of the PA signal emanating from the gold nanocomposite and the graphite/PDMS mixture. The schematic diagram of the experimental setup is shown in Figure 10, where the medium in which the experiments were performed was water. A 527 nm Nd:YLF nanosecond laser (Falcon 527-30-M, Quantronix) with a pulse width of 150 ns and a repetition rate of 1 kHz was used as the optical radiation source. The laser beam was split into two beams by a beam splitter. One of the beams was input into a photodetecter (PDA10CS, Thorlabs) as a reference signal and the other beam was coupled into a multi-mode fiber (MMF) (M40L02, Thorlabs) with a core diameter of 400 μιη through a coupler (F810SMA-543, Thorlabs). The laser pulse was excited on the glass slide coated with the gold nanocomposite or

graphite/PDMS mixture through the optical fiber. A hydrophone (HGL-0200, Onda) was applied to collect the acoustic signals. The reference signals and the acoustic signals were transmitted to a data acquisition system (DAQ) (M2L4032, Spectrum) with a sampling rate of 50 MHz.

Results from gold nanocomposite

The optimal generated ultrasound results by the gold nanocomposite are illustrated in Figure 11. The distance between the hydrophone and the sample was 1.8 mm. The peak to peak amplitude of the acoustic signal can be calculated as 189.49 kPa under the energy density of 13 mJ/cm . The oscillations behind the peak were caused by the reflections between the hydrophone and the gold nanocomposite film.

Results from graphite within PDMS

Acoustic signals generated from the graphite/PDMS is shown in Figure 12. The laser energy density was 0.86 mJ/cm . The distance between the hydrophone and the sample was 2.26 mm. The peak to peak amplitude of the acoustic signal can be calculated as 48.89 kPa.

Conclusion

Acoustic signals generated by the gold nanocomposite and the graphite/PDMS were obtained. The teachings of all patents, published applications and references cited herein are incorporated by reference in their entirety.

While this invention has been particularly shown and described with references to example embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.