DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant' s arguments, filed 7/9/2026, have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Applicants have amended their claims, filed 7/9/2026, and therefore rejections newly made in the instant office action have been necessitated by amendment.
Claims 1-20 are the currently pending claims hereby under examination. Claims 1, 10, 17, and 19 have been amended.
Claim Objections
Claim 1 is objected to because of the following informalities:
In claim 1, line 10: "based on a detected reflection of the continuous optical signal" appears intended to refer to the previously detected reflection and should be "based on the detected reflection of the continuous optical signal”.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-7 and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Reza et al. (US-20160113507-A1), hereinafter referred to as Reza, in view of Antonelli et al. (US-20090299197-A1), hereinafter referred to as Antonelli, and further in view of Wood (US-20130109947-A1), hereinafter referred to as Wood.
Regarding claim 1, Reza teaches a method comprising: transmitting a continuous optical signal toward a skin of the user, the skin being proximate to a blood vessel of the user (Reza, ¶[0116]: "For the receiver arm a continuous wavelength (CW) C-band laser with 100-kHz linewidth...was used" and ¶[0114]: "Detection laser 14 may be a continuous wave laser", Reza expressly and unambiguously teaches that the interrogation or detection optical signal is a continuous-wave (CW) optical signal; Abstract: "an interrogation beam incident on the sample at the excitation location, a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals" and ¶[0049]: the acoustic signatures are interrogated using "a long-coherence length probe beam...co-focused and co-aligned with the excitation spots on sample 18", Reza teaches that the CW interrogation beam is directed toward the sample at the target location; ¶[0046]: "capable of in vivo optical-resolution photoacoustic microscopy" and ¶[0127]: "FIGS. 19a-19d depict in vivo PARS images of a mouse ear, and FIGS. 23a-23c and 24 show in vivo PARS images of a 100 g rat's ear", Reza teaches that the interrogation beam is used in vivo on the ear tissue of a living subject (the ear is skin-covered tissue directly overlying blood vessels, supporting that the optical signal is directed toward the skin of a living subject); ¶[0109]: "Surface pressure modulation can cause surface oscillations and the reflection of the interrogation beam from this oscillating surface can be a source of detected signal", Reza teaches that the returning portion of the interrogation beam includes reflection from the oscillating outer tissue surface; ¶[0105]: T_t is "the transmission intensity coefficient at the air-tissue interface", Reza further teaches that this surface reflection occurs at the air-tissue interface, i.e., the outer surface of the biological tissue, such that the detected returning interrogation beam includes reflection from the tissue surface previously established as the skin of the living subject; ¶[0123]: "FIG. 14a shows multifocus PARS images revealing both capillary beds and bigger blood vessels", Reza teaches that the biological tissue interrogated by the PARS system includes capillary beds and larger blood vessels underlying the interrogated surface, supporting that the interrogated skin surface is proximate to a blood vessel); during the transmitting of the continuous optical signal, causing generation of one or more acoustic signals from a blood vessel of the user by transmitting one or more pulsed optical signals toward the blood vessel (Reza, Abstract: "an excitation beam configured to generate ultrasonic signals in the sample at an excitation location", Reza teaches an excitation beam configured to generate ultrasonic signals in the sample; ¶[0046]: "Photoacoustic imaging is an emerging biomedical imaging modality that uses laser light to excite tissues. Energy absorbed by chromophores or any other absorber is converted to acoustic waves due to thermo-elastic expansion", Reza teaches that laser excitation of tissue generates acoustic waves; ¶[0047]: "at 532-nm excitation wavelength, imaging a capillary with 500 mJ/cm² local fluence would result in an initial pressure on the order of 100 MPa locally", Reza expressly teaches excitation of a capillary, i.e., a blood vessel, to generate an acoustic pressure response; ¶[0060]: "In one example, a nanosecond-pulsed laser was used" and ¶[0133]: "laser pulses should be preferably shorter than 2 µm/1500 m/s = 1.3 ns, which would require a laser with pulse widths of a nanosecond or shorter", Reza teaches pulsed laser excitation with nanosecond or shorter pulse widths); during the generation of the one or more acoustic signals, detecting a reflection of the continuous optical signal from the skin of the user (Reza, Abstract: "a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals" and "a detector that detects the returning portion of the interrogation beam", Reza teaches detecting a returning portion of the interrogation beam from the sample during the photoacoustic process; ¶[0047]: "large optically-focused photoacoustic signals are detected as close to the photoacoustic source as possible, which is done optically by co-focusing an interrogation beam with the excitation spot. A long-coherence length interrogation laser is preferably used with low amplitude and phase noise to read-out the large local photoacoustic vibrations interferometrically using a novel architecture designed to optimize received signal intensities", Reza teaches optical detection of local photoacoustic vibrations using the CW interrogation laser at the excitation site; ¶[0015]: "a portion of the interrogation beam returning from the sample...is indicative of the generated ultrasonic signals", Reza further teaches that the detected return corresponds to interrogation-beam detection at the photoacoustic excitation location; ¶[0109]: "Surface pressure modulation can cause surface oscillations and the reflection of the interrogation beam from this oscillating surface can be a source of detected signal", Reza teaches detecting the reflection of the CW interrogation beam from the tissue surface during acoustic signal generation). Reza therefore teaches noncontact, in vivo interrogation at an air-tissue surface over vascular structures (Reza, ¶[0046], ¶[0105], ¶[0123], ¶[0127]).
Also regarding claim 1, with respect to the limitation reciting based on a detected reflection of the continuous optical signal, determining a displacement of the skin of the user caused by the one or more acoustic signals generated from the blood vessel by the one or more pulsed optical signals, Reza expressly teaches that 532 nm excitation of a capillary generates an initial acoustic pressure response (Reza, ¶[0047]). Reza further teaches that acoustic signals from an exemplary optically heated blood absorber, including an isolated red blood cell, propagate to the tissue surface and produce phase modulation of the reflected interrogation light. Reza further teaches that surface pressure modulation causes surface oscillations, quantitatively relates surface pressure to particle velocity and displacement using Δz = v/ω, and identifies the resulting reflected-light phase modulation as readily measurable despite the disclosed low-pass effect (Reza, ¶[0109]). Reza models the surface-reflected optical field as a function of the surface displacement (Reza, ¶[0110]). Reza also teaches detecting probing-beam phase oscillations through interferometry or laser Doppler vibrometry and using PARS as an optical vibrometer for noncontact measurement of displacement caused by ultrasound (Reza, ¶[0068], ¶[0081]-[0082]). Paragraph [0082] demonstrates the optical displacement readout using a piezoelectric acoustic source, while paragraph [0109] supplies the corresponding photoacoustic source-to-surface-oscillation mechanism for an optically heated blood absorber. These disclosures teach the claimed photoacoustic source-to-surface-displacement-to-reflection relationship.
Reza does not expressly state in a single photoacoustic blood-vessel embodiment that its processor determines the skin displacement from the detected surface reflection.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Reza by configuring Reza's disclosed processor to determine the skin displacement from the detected phase modulation using Reza's disclosed pressure-to-displacement relationship and optical-vibrometer processing. A person of ordinary skill in the art would have been motivated to perform that calculation because Reza expressly presents PARS as an optical vibrometer for noncontact displacement measurement and already processes the returning interrogation beam to calculate information about the sample (Reza, ¶[0018], ¶[0081]-[0082]). There would have been a reasonable expectation of success because Reza supplies both the quantitative relationship and a demonstrated noncontact optical displacement readout. This modification does not substitute the piezoelectric transducer for the claimed blood-vessel source; the transducer example demonstrates Reza's disclosed optical-vibrometer readout, while Reza's separate photoacoustic model supplies the claimed blood-vessel source and causal chain.
Also regarding claim 1, the modified Reza does not expressly teach based on the displacement of the skin of the user, determining a physiological parameter of the user. Rather, Reza teaches detecting and processing the returning portion of the interrogation beam, including that "there may be a processor that calculates an image of the sample based on the returning portion of the interrogation beam" (Reza, ¶[0018]). Reza further discloses that photoacoustic imaging may be used for functional imaging applications such as imaging blood oxygen saturation (Reza, ¶[0046]), indicating that the detected interrogation signal can be processed to derive biological information, but the modified Reza does not expressly disclose determining a physiological parameter of the user based on the determined skin displacement.
Antonelli expressly teaches this limitation. Antonelli teaches a "non-contact method and apparatus for continuously monitoring physiological events such as the anatomical blood pressure waveform" (Antonelli, ¶[0028]). Antonelli teaches directing a continuous-wave laser beam toward the skin over an artery and detecting the reflected beam: "[a] low-power (1 mW), continuous, red laser beam is directed onto the measurement surface. By interfering the detected beam that was reflected by the measurement surface with a reference beam within the LDV, a measure of the surface velocity is obtained" (Antonelli, ¶[0019]). Antonelli teaches that the computer correlates the detected optical return signal to the blood pressure in the underlying artery: "The computer can be calibrated to correlate the velocity and motion of the skin surface to the pressure of the blood in the artery beneath skin surface" (Antonelli, ¶[0037]). Antonelli further teaches that "[i]t is necessary to convert the measured velocity into a skin displacement signal. This is a critical aspect of the invention in order to provide medical personnel a waveform that is similar to those achieved by catheter pressure sensor" (Antonelli, ¶[0043]). Antonelli therefore expressly teaches determining a physiological parameter (blood pressure) based on the detected reflection of a continuous optical signal from skin proximate to a blood vessel.
Wood further supplies a photoacoustically matched relationship between the detected response and the physiological parameter. Wood teaches that an acoustic pressure signal produced by optical absorption may be analyzed to reveal blood-vessel dimensions and changes in vessel size over the cardiac cycle (Wood, ¶[0002]-[0004]). Wood expressly explains that pressure signals originating at the front and back vessel boundaries travel through the subject's tissue and reach the detector sequentially because the boundary-to-detector path lengths differ (Wood, ¶[0058]). The resulting time-separated peaks identify the vessel boundaries, and their separation varies with blood pressure over the cardiac cycle (Wood, ¶[0057]-[0059]). Reza teaches that propagating acoustic pressure reaching the tissue surface produces particle velocity and surface displacement that phase modulates the reflected interrogation beam, and Reza digitizes that return at 200 MSamples/s (Reza, ¶[0109], ¶[0117]). Although Reza notes that surface modulation has a 1/ω dependence and thus an inherent low-pass effect, Reza states in the same paragraph that such signals are readily measurable (Reza, ¶[0109]). Reza's own receiver uses a 150 MHz-bandwidth InGaAs photodiode, a 1 MHz to 20 MHz band-pass filter in the detection chain, and digitization at 200 MSamples/s, thereby expressly demonstrating that the receiver is configured to detect megahertz-frequency content (Reza, ¶[0117]). Reza also demonstrates real-time displacement detection over a 10 MHz bandwidth (Reza, ¶[0082]). The timing required for Wood's vessel-boundary analysis falls within that demonstrated range. Wood teaches that vessel size may be measured from the time difference between the two boundary peaks and states that acoustic travel time is R/c, where c is the speed of sound in tissue; Wood also uses a 1 mm vessel-diameter scale in an exemplary embodiment (Wood, ¶[0022], ¶[0064], ¶[0076]). Reza uses c = 1500 m/s for tissue (Reza, ¶[0133]). Thus, 1 mm / 1500 m/s is approximately 667 ns, corresponding to a resolvable-feature rate of approximately 1.5 MHz, within Reza's 1 MHz to 20 MHz detection band. Using Reza's optical surface-displacement readout instead of Wood's contacting acoustic detector changes the transduction at the tissue surface, but it does not change the propagation paths or relative arrival times of the front- and back-boundary pressure components. Reza's displacement waveform therefore preserves the boundary timing used in Wood's peak-separation analysis. Wood further teaches determining vessel size from the photoacoustic signal and determining blood pressure from the vessel size and calibration values (Wood, ¶[0074]-[0078]). Wood thus establishes that the photoacoustic response optically detected through Reza's surface displacement contains vascular information suitable for determining blood pressure.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza in view of Antonelli and Wood by configuring the processor to determine a physiological parameter based on the photoacoustically caused skin displacement detected by Reza and, to the extent necessary, by applying Reza's noncontact tissue-surface interrogation to human skin over a blood vessel. A person of ordinary skill in the art would have been motivated to employ Antonelli's human-skin measurement arrangement because Antonelli teaches that reflected-light measurement of skin displacement over an artery permits noninvasive acquisition of cardiovascular information from an accessible skin surface (Antonelli, ¶[0019]-[0020], [0037], [0043]). A person of ordinary skill in the art would separately have been motivated to apply Wood's vessel-boundary and blood-pressure processing because Wood expressly teaches that the temporal separation between photoacoustic responses from opposing vessel boundaries provides vessel dimension and that the measured vessel dimension is used to determine blood pressure (Wood, ¶[0057]-[0069], [0074]-[0078]). Reza detects the same underlying photoacoustic pressure response through the resulting tissue-surface displacement, and its receiver preserves the boundary timing used by Wood. The modifications therefore would have predictably permitted Reza's noncontact optical receiver to obtain the vessel-dimensional information Wood identifies and determine blood pressure while using Antonelli's established human-skin measurement location. There would have been a reasonable expectation of success because Reza already processes the returning interrogation beam, Wood demonstrates the photoacoustic vessel-size and blood-pressure calculations, and Antonelli demonstrates reflected-light measurement of human-skin motion over an artery. The combination does not equate vessel distension with skin displacement or substitute Antonelli's passive cardiac displacement for Reza's photoacoustically caused displacement.
Regarding claim 2, claim 2 further recites a method comprising: determining a physical characteristic of the blood vessel based at least on the detected reflection of the continuous optical signal; and determining the physiological parameter based at least on the physical characteristic of the blood vessel. The modified Reza teaches the amended claim 1 as described above and further teaches processing the returning interrogation beam to calculate an image of the sample (Reza, ¶[0018]). Reza also teaches imaging vascular structures from microvessels to larger blood vessels (Reza, ¶[0004], ¶[0123]). Reza does not expressly identify a discrete blood-vessel characteristic determined from the reflected optical signal as the intermediate basis for determining the physiological parameter.
Wood expressly teaches the recited two-stage determination in the same photoacoustic context as Reza. Wood teaches that the photoacoustic signal includes peaks corresponding to the front and back boundaries of a blood vessel and that the time difference between those peaks identifies vessel diameter (Wood, ¶[0057]-[0059]). Wood further teaches determining blood-vessel size based on the photoacoustic signal and determining blood pressure based on the measured vessel size and calibration values (Wood, ¶[0060]-[0069], ¶[0074]-[0078]). Vessel diameter or size is a physical characteristic of the blood vessel, and Wood expressly uses that characteristic as the basis for the physiological-parameter determination.
Antonelli additionally teaches that the reflected continuous-wave beam encodes skin-surface displacement and that the measured displacement is correlated to the pressure in the underlying artery (Antonelli, ¶[0020], ¶[0030], ¶[0032], ¶[0037], ¶[0043]). Antonelli therefore corroborates that vascular information represented in a reflected-light displacement signal may be used to determine blood-pressure information, while Wood supplies the expressly identified vessel characteristic and the matched photoacoustic processing.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza to determine vessel size or diameter as the physical characteristic represented by Reza's optically detected photoacoustic response and to determine blood pressure from that characteristic using Wood's calibration. A person of ordinary skill in the art would have been motivated to select vessel size or diameter because Wood expressly identifies vessel dimension from the temporal separation of the photoacoustic boundary responses and uses that measured dimension in determining blood pressure (Wood, ¶[0057]-[0069], [0074]-[0078]). Applying Wood's processing to Reza's displacement-encoded photoacoustic response therefore would have predictably obtained the same measurable intermediate expressly used by Wood for its blood-pressure determination. The modification would have had a reasonable expectation of success because Wood demonstrates the complete photoacoustic-signal-to-vessel-size-to-blood-pressure process, Reza detects and processes the same type of photoacoustic response through surface displacement, and Antonelli confirms the physiological utility of optically measured surface motion over a vessel.
Regarding claim 3, claim 3 further recites a method wherein the physical characteristic of the blood vessel comprises distension or pulse wave velocity of the blood vessel, and wherein the physiological parameter comprises blood pressure. The modified Reza system teaches vessel size or diameter as the physical characteristic and blood pressure as the physiological parameter as described regarding claim 2. The combination does not rely on the amended photoacoustically caused skin displacement itself as the recited vessel distension.
As to blood pressure as the physiological parameter, Wood expressly teaches determining blood pressure from blood-vessel size and calibration values (Wood, ¶[0004], ¶[0067]-[0069], ¶[0077]-[0078]). Antonelli additionally teaches correlating optically measured skin motion to the pressure of the blood in the underlying artery and producing a blood-pressure waveform (Antonelli, ¶[0037]-[0038], ¶[0043]).
As to distension as the physical characteristic, Wood expressly teaches that a blood vessel stretches in response to changes in blood pressure and identifies distensibility as a physiological feature that quantifies the response (Wood, ¶[0003]). Wood defines distensibility using change in vessel volume per change in pressure and teaches collecting photoacoustic measurements over the cardiac cycle to capture expansion and contraction of the vessel (Wood, ¶[0060]-[0065]). Wood further teaches that a series of vessel-size measurements corresponds to the change in blood pressure over the cardiac cycle (Wood, ¶[0076]). These measured changes in vessel size constitute vessel distension, distinct from the photoacoustically caused skin displacement through which Reza optically detects the response.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza to characterize the physical characteristic as vessel distension and determine blood pressure from that characteristic. A person of ordinary skill in the art would have been motivated to characterize the repeatedly measured vessel dimension as distension because Wood expressly monitors expansion and contraction through successive photoacoustic vessel-size measurements over the cardiac cycle and uses the vessel-size relationship in its blood-pressure calibration (Wood, ¶[0060]-[0065], [0076]-[0078]). Applying that processing to Reza's optically detected photoacoustic response therefore would have predictably produced the distension measurement and blood-pressure determination taught by Wood. There would have been a reasonable expectation of success based on Wood's demonstrated photoacoustic measurements and calibration process, while Antonelli further supports the clinical utility of noncontact optical monitoring of vessel-associated motion.
Regarding claim 4, the modified Reza teaches a method further comprising obtaining an image representation of at least the reflection of the continuous optical signal, wherein the determining of the physical characteristic of the blood vessel is based on the image representation (Reza, ¶[0018]: "there may be a processor that calculates an image of the sample based on the returning portion of the interrogation beam", Reza expressly teaches that the returning portion of the interrogation beam, i.e., the detected reflection of the CW interrogation signal, is processed by a processor to calculate an image of the sample, which is an image representation of at least the reflection of the continuous optical signal as recited in the claim; ¶[0123]: "FIG. 14a shows multifocus PARS images revealing both capillary beds and bigger blood vessels", Reza teaches that the PARS images calculated from the returning interrogation beam reveal vascular structures, constituting an image representation from which the physical characteristic of the blood vessel is determined; ¶[0004]: "Photoacoustic microscopy has shown significant potential for imaging vascular structures from macro-vessels all the way down to micro-vessels", Reza further teaches that characterization of vascular structures, i.e., determining a physical characteristic of the blood vessel, is based on those PARS images, as recited in the claim).
Regarding claim 5, the modified Reza teaches a method wherein the determining of the physical characteristic of the blood vessel comprises determining a displacement of the skin of the user, the physical characteristic of the blood vessel determined based on the displacement of the skin. Reza teaches determining photoacoustically caused surface displacement from phase modulation of the reflected interrogation beam as discussed regarding claim 1 (Reza, ¶[0068], ¶[0081]-[0082], ¶[0109]). Reza also teaches processing the returning beam to calculate information about the vascular sample (Reza, ¶[0018], ¶[0123]).
Wood teaches that pressure signals originating at the front and back vessel boundaries travel through tissue and arrive sequentially because their path lengths differ, and that the time separation between the resulting peaks identifies vessel diameter (Wood, ¶[0057]-[0059]). Reza teaches the intervening surface transduction: when those propagating pressure components reach the tissue surface, acoustic pressure produces particle velocity and displacement that phase modulates the reflected interrogation beam (Reza, ¶[0068], ¶[0081]-[0082], ¶[0109]). That surface transduction does not alter the components' relative arrival times. Reza further digitizes the detected return at 200 MSamples/s, providing a time-resolved displacement waveform (Reza, ¶[0117]). A person of ordinary skill in the art would therefore have understood that the measured displacement waveform preserves the temporally varying acoustic response from which Wood's vessel-boundary timing and vessel-size information may be obtained. Reza's disclosed low-pass effect does not preclude use of that timing information for the reasons discussed regarding claim 1. Antonelli additionally teaches extracting skin displacement from a reflected continuous optical signal and using that displacement signal for blood-pressure monitoring (Antonelli, ¶[0020], ¶[0030]-[0032], ¶[0037], ¶[0043]). Thus, the references teach first determining the skin displacement and then determining the vessel characteristic based on the displacement-encoded photoacoustic response, without treating skin displacement itself as vessel diameter or distension.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza by applying Wood's time-domain vessel-boundary processing to the photoacoustic response represented by Reza's measured skin displacement. A person of ordinary skill in the art would have been motivated to apply that processing because Wood teaches that temporal separation between the photoacoustic responses from opposing vessel boundaries represents vessel dimension, while Reza teaches that its measured surface displacement represents the time-varying photoacoustic pressure response. Reza's receiver also passes the relevant timing band. Applying Wood's analysis to Reza's displacement-encoded response therefore would have predictably extracted vessel dimension without changing the underlying boundary timing being measured. There would have been a reasonable expectation of success because Reza provides the quantitative pressure-to-velocity-to-displacement relationship and high-rate digitization needed to recover the time-varying response, Wood derives vessel size from the timing of that response, and Antonelli demonstrates extraction and physiological use of reflected-light skin displacement.
Regarding claim 6, the modified Reza teaches a method wherein the determining of the displacement of the skin of the user comprises using a focus differential indicative of a distance to the skin, a frequency difference associated with the reflection of the continuous optical signal, a phase difference associated with the reflection of the continuous optical signal, or a combination thereof (Reza, ¶[0082]: "The reflected near-infrared beam from the sample is phase-modulated at the ultrasound frequency, and a beat-intensity can be detected", Reza expressly teaches that the reflected continuous optical signal is phase-modulated and that the resulting beat signal is detected, satisfying the phase-difference alternative; ¶[0068]: "phase (and maybe amplitude) oscillations in the probing receiver beam can be detected using interferometry", Reza further expressly teaches detection of phase oscillations in the receiver beam and independently teaches laser-Doppler detection supporting the frequency-difference alternative; ¶[0110]: Reza models the surface-reflected optical field as a function of surface displacement, further tying the detected phase of the reflected field to the displacement; ¶[0047]: Reza corroborates use of a long-coherence interrogation laser to "read-out the large local photoacoustic vibrations interferometrically").
Regarding claim 7, the modified Reza teaches a method wherein the one or more pulsed optical signals comprise one or more optical signals emitted by a first light source, the continuous optical signal comprises a continuous optical signal emitted by a second light source, and the first light source and the second light source are disposed at different locations of a device (Reza, ¶[0060]: "In one example, a nanosecond-pulsed laser was used", Reza expressly teaches a dedicated pulsed laser source for generating the excitation optical signals, corresponding to the first light source as recited in the claim; ¶[0116]: "For the receiver arm a continuous wavelength (CW) C-band laser with 100-kHz linewidth (TLK-L1550R, Thorlabs Inc., New Jersey) was used", Reza expressly teaches a dedicated CW laser source for the interrogation beam, corresponding to the second light source as recited in the claim; ¶[0114] and FIG. 20: Reza depicts the experimental PARS system in FIG. 20, showing pulsed laser 12 and detection laser 14 as entirely separate, spatially distinct components within the system architecture, with their respective beams combined only downstream at dual beam combiner 2218 before reaching the sample, expressly teaching that the first and second light sources occupy different locations within the device; ¶[0118] and FIG. 22: Reza further depicts in FIG. 22 an alternative system configuration in which "pulse laser 12 provides an additional beam to polarization maintaining single mode fiber 2402, lens system 42, and then to beam combiner unit 30" while continuous wave lasers 2404 and 2406 provide separate beams that are likewise combined at beam combiner unit 30 before reaching sample 18, again expressly teaching two light sources disposed at different locations within the device as recited in the claim).
Regarding claim 17, Reza teaches that a non-transitory computer-readable apparatus comprising a storage medium, the storage medium comprising a plurality of instructions configured to, when executed by a control system, cause an apparatus to (Reza, ¶[0051]: the PARS detection unit 22 is described as comprising "a photodiode 46, amplifier 48, data acquisition unit 50 and a computer", Reza expressly teaches that the PARS system includes a computer as an integral component of the detection and data processing architecture; ¶[0018]: "there may be a processor that calculates an image of the sample based on the returning portion of the interrogation beam" and claim 9: "a processor that calculates an image of the sample based on the returning portion of the interrogation beam", Reza further teaches that the computer executes defined processing operations on the detected optical return signal; a computer of the type expressly disclosed in Reza at ¶[0051] necessarily and implicitly comprises a non-transitory computer-readable storage medium, such as a hard disk drive, ROM, or flash memory, on which the instructions controlling the data acquisition and processing operations are stored, as such storage is a fundamental and inseparable architectural component of any computer; a person of ordinary skill in the art would therefore have understood that the computer disclosed in Reza at ¶[0051] constitutes a non-transitory computer-readable apparatus comprising a storage medium on which instructions for performing the recited steps are stored, and therefore necessarily includes stored instructions controlling Reza's disclosed data-acquisition and processing operations): transmit a continuous optical signal toward a skin of the user, the skin being proximate to a blood vessel of the user (Reza, ¶[0116]: "For the receiver arm a continuous wavelength (CW) C-band laser with 100-kHz linewidth...was used" and ¶[0114]: "Detection laser 14 may be a continuous wave laser", Reza expressly and unambiguously teaches that the interrogation or detection optical signal is a continuous-wave (CW) optical signal; Abstract: "an interrogation beam incident on the sample at the excitation location, a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals" and ¶[0049]: the acoustic signatures are interrogated using "a long-coherence length probe beam...co-focused and co-aligned with the excitation spots on sample 18", Reza teaches that the CW interrogation beam is directed toward the sample at the target location; ¶[0046]: "capable of in vivo optical-resolution photoacoustic microscopy" and ¶[0127]: "FIGS. 19a-19d depict in vivo PARS images of a mouse ear, and FIGS. 23a-23c and 24 show in vivo PARS images of a 100 g rat's ear", Reza teaches that the interrogation beam is used in vivo on the ear tissue of a living subject (the ear is skin-covered tissue directly overlying blood vessels, supporting that the optical signal is directed toward the skin of a living subject); ¶[0109]: "Surface pressure modulation can cause surface oscillations and the reflection of the interrogation beam from this oscillating surface can be a source of detected signal", Reza teaches that the returning portion of the interrogation beam includes reflection from the oscillating outer tissue surface; ¶[0105]: T_t is "the transmission intensity coefficient at the air-tissue interface", Reza further teaches that this surface reflection occurs at the air-tissue interface, i.e., the outer surface of the biological tissue, such that the detected returning interrogation beam includes reflection from the tissue surface previously established as the skin of the living subject; ¶[0123]: "FIG. 14a shows multifocus PARS images revealing both capillary beds and bigger blood vessels", Reza teaches that the biological tissue interrogated by the PARS system includes capillary beds and larger blood vessels underlying the interrogated surface, supporting that the interrogated skin surface is proximate to a blood vessel); during the transmitting of the continuous optical signal, cause generation of one or more acoustic signals from a blood vessel of the user by transmitting one or more pulsed optical signals toward the blood vessel (Reza, Abstract: "an excitation beam configured to generate ultrasonic signals in the sample at an excitation location", Reza teaches an excitation beam configured to generate ultrasonic signals in the sample; ¶[0046]: "Photoacoustic imaging is an emerging biomedical imaging modality that uses laser light to excite tissues. Energy absorbed by chromophores or any other absorber is converted to acoustic waves due to thermo-elastic expansion", Reza teaches that laser excitation of tissue generates acoustic waves; ¶[0047]: "at 532-nm excitation wavelength, imaging a capillary with 500 mJ/cm² local fluence would result in an initial pressure on the order of 100 MPa locally", Reza expressly teaches excitation of a capillary, i.e., a blood vessel, to generate an acoustic pressure response; ¶[0060]: "In one example, a nanosecond-pulsed laser was used" and ¶[0133]: "laser pulses should be preferably shorter than 2 µm/1500 m/s = 1.3 ns, which would require a laser with pulse widths of a nanosecond or shorter", Reza teaches pulsed laser excitation with nanosecond or shorter pulse widths); during the generation of the one or more acoustic signals, detect a reflection of the continuous optical signal from the skin of the user (Reza, Abstract: "a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals" and "a detector that detects the returning portion of the interrogation beam", Reza teaches detecting a returning portion of the interrogation beam from the sample during the photoacoustic process; ¶[0047]: "large optically-focused photoacoustic signals are detected as close to the photoacoustic source as possible, which is done optically by co-focusing an interrogation beam with the excitation spot. A long-coherence length interrogation laser is preferably used with low amplitude and phase noise to read-out the large local photoacoustic vibrations interferometrically using a novel architecture designed to optimize received signal intensities", Reza teaches optical detection of local photoacoustic vibrations using the CW interrogation laser at the excitation site; ¶[0015]: "a portion of the interrogation beam returning from the sample...is indicative of the generated ultrasonic signals", Reza further teaches that the detected return corresponds to interrogation-beam detection at the photoacoustic excitation location; ¶[0109]: "Surface pressure modulation can cause surface oscillations and the reflection of the interrogation beam from this oscillating surface can be a source of detected signal", Reza teaches detecting the reflection of the CW interrogation beam from the tissue surface during acoustic signal generation).
Also regarding claim 17, with respect to the requirement that the instructions cause the apparatus to, based on the detected reflection of the continuous optical signal, determine a displacement of the skin of the user caused by the one or more acoustic signals generated from the blood vessel by the one or more pulsed optical signals, Reza expressly teaches that 532 nm excitation of a capillary generates an initial acoustic pressure response (Reza, ¶[0047]). Reza further teaches that photoacoustic pressure from an optically heated blood absorber propagates to the tissue surface, causes surface displacement, and phase modulates the reflected interrogation beam, and Reza provides the quantitative pressure-to-displacement relationship (Reza, ¶[0109]-[0110]). Reza also teaches interferometric or laser-Doppler detection and use of PARS as an optical vibrometer for noncontact displacement measurement (Reza, ¶[0068], ¶[0081]-[0082]). Paragraph [0082] demonstrates the optical displacement readout using a piezoelectric acoustic source, while paragraph [0109] supplies the corresponding photoacoustic source-to-surface-oscillation mechanism for an optically heated blood absorber. These disclosures teach the claimed photoacoustic source-to-surface-displacement-to-reflection relationship.
Reza does not expressly state in a single photoacoustic blood-vessel embodiment that the stored instructions cause the apparatus to calculate the skin displacement from the detected surface reflection.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Reza by configuring the stored instructions executed by Reza's computer to determine the skin displacement from the detected phase modulation using Reza's disclosed pressure-to-displacement relationship and optical-vibrometer processing. A person of ordinary skill in the art would have been motivated to implement that calculation in the stored instructions because Reza expressly presents PARS as an optical vibrometer for noncontact displacement measurement and already uses its computer to process the returning interrogation beam (Reza, ¶[0018], ¶[0051], ¶[0081]-[0082]). There would have been a reasonable expectation of success because Reza supplies the quantitative relationship, a demonstrated noncontact optical displacement readout, and an existing computer-based acquisition and processing architecture. This modification does not substitute the piezoelectric transducer for the claimed blood-vessel source; the transducer example demonstrates Reza's disclosed optical-vibrometer readout, while Reza's separate photoacoustic model supplies the claimed blood-vessel source and causal chain.
Also regarding claim 17, the modified Reza does not expressly teach based on the displacement of the skin of the user, determining a physiological parameter of the user. Rather, Reza teaches detecting and processing the returning portion of the interrogation beam, including that "there may be a processor that calculates an image of the sample based on the returning portion of the interrogation beam" (Reza, ¶[0018]). Reza further discloses that photoacoustic imaging may be used for functional imaging applications such as imaging blood oxygen saturation (Reza, ¶[0046]), indicating that the detected interrogation signal can be processed to derive biological information, but the modified Reza does not expressly disclose determining a physiological parameter of the user based on the determined skin displacement.
Antonelli expressly teaches this limitation. Antonelli teaches a "non-contact method and apparatus for continuously monitoring physiological events such as the anatomical blood pressure waveform" (Antonelli, ¶[0028]). Antonelli teaches directing a continuous-wave laser beam toward the skin over an artery and detecting the reflected beam: "[a] low-power (1 mW), continuous, red laser beam is directed onto the measurement surface. By interfering the detected beam that was reflected by the measurement surface with a reference beam within the LDV, a measure of the surface velocity is obtained" (Antonelli, ¶[0019]). Antonelli teaches that the computer correlates the detected optical return signal to the blood pressure in the underlying artery: "The computer 30 can be calibrated to correlate the velocity and motion of the skin surface 26 to the pressure of the blood in the artery beneath skin surface" (Antonelli, ¶[0037]). Antonelli further teaches that "[i]t is necessary to convert the measured velocity into a skin displacement signal. This is a critical aspect of the invention in order to provide medical personnel a waveform that is similar to those achieved by catheter pressure sensor" (Antonelli, ¶[0043]). Antonelli therefore expressly teaches determining a physiological parameter (blood pressure) based on the detected reflection of a continuous optical signal from skin proximate to a blood vessel.
Wood further teaches that pressure signals originating at the front and back vessel boundaries travel through tissue and arrive sequentially because of their different path lengths, and Wood uses the resulting peak timing to identify vessel size and determine blood pressure (Wood, ¶[0057]-[0059], ¶[0060]-[0069], ¶[0074]-[0078]). Reza independently teaches that propagating acoustic pressure reaching the tissue surface produces particle velocity and displacement that phase modulates the reflected interrogation beam, and Reza digitizes the return at 200 MSamples/s (Reza, ¶[0109], ¶[0117]). Although Reza notes a 1/ω low-pass effect, Reza states that the surface-modulation signals are readily measurable and discloses a 1 MHz to 20 MHz band-pass filter in the receiver (Reza, ¶[0109], ¶[0117]). Wood uses a 1 mm vessel-diameter scale and measures vessel size from boundary-peak timing, while Reza uses a tissue sound speed of 1500 m/s (Wood, ¶[0022], ¶[0064], ¶[0076]; Reza, ¶[0133]). Thus, a 1 mm acoustic path difference corresponds to approximately 667 ns, or a resolvable-feature rate of approximately 1.5 MHz, within Reza's disclosed detection band. Reza's optical surface-displacement readout changes the transduction at the tissue surface but does not change the propagation paths or relative arrival times of Wood's front- and back-boundary pressure components. Wood therefore supplies a physiologically matched photoacoustic basis for the blood-pressure determination performed by the stored instructions.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza in view of Antonelli and Wood by configuring the stored instructions to determine a physiological parameter based on the photoacoustically caused skin displacement and, to the extent necessary, to apply Reza's noncontact tissue-surface interrogation to human skin over a blood vessel. A person of ordinary skill in the art would have been motivated to implement Antonelli's human-skin measurement arrangement because Antonelli teaches that reflected-light measurement of skin displacement over an artery permits noninvasive acquisition of cardiovascular information from an accessible skin surface (Antonelli, ¶[0019]-[0020], [0037], [0043]). A person of ordinary skill in the art would separately have been motivated to implement Wood's vessel-boundary and blood-pressure processing because Wood expressly teaches deriving vessel dimension from the temporal separation between photoacoustic boundary responses and using the measured vessel dimension to determine blood pressure (Wood, ¶[0057]-[0069], [0074]-[0078]). Reza detects the same underlying response through tissue-surface displacement, and its receiver preserves the timing used by Wood. The stored-instruction modifications therefore would have predictably enabled Reza's existing computer to obtain Wood's vessel-dimensional information and determine blood pressure at Antonelli's established human-skin measurement location. There would have been a reasonable expectation of success because Reza already uses a computer to process the optical return, Wood demonstrates the photoacoustic calculations, and Antonelli demonstrates reflected-light measurement of human-skin motion over an artery.
Regarding claim 18, the modified Reza teaches claim 17 as described above. Claim 18 further recites that the plurality of instructions are further configured to, when executed by the control system, cause the apparatus to: determine a physical characteristic of the blood vessel based at least on the reflection of the continuous optical signal, wherein the physical characteristic of the blood vessel comprises a distension experienced by the blood vessel during the generation of the one or more acoustic signals, or a pulse wave velocity (PWV) of the blood vessel; and determine the physiological parameter of the user based on the physical characteristic of the blood vessel, wherein the physiological parameter of the user comprises a blood pressure of the user. Reza teaches processing the optically detected photoacoustic response to calculate information about vascular samples (Reza, ¶[0018], ¶[0123]), but the modified Reza does not expressly determine vessel distension or pulse wave velocity from the reflection and then determine blood pressure based on that physical characteristic.
Wood teaches determining vessel dimensions from the photoacoustic response. Wood explains that acoustic-pressure peaks correspond to the front and back boundaries of the vessel and that the peak separation identifies vessel diameter (Wood, ¶[0057]-[0059]). Wood further teaches repeatedly acquiring photoacoustic measurements over the cardiac cycle to capture expansion and contraction of the vessel and using the resulting change in vessel size to establish distensibility (Wood, ¶[0060]-[0065]). This expansion and contraction constitutes the recited vessel distension.
As to the requirement that the distension is experienced by the blood vessel during generation of the acoustic signals, each of Wood's vessel-size measurements is obtained by generating and detecting a photoacoustic pressure response while the vessel occupies a particular expanded or contracted state in the cardiac cycle (Wood, ¶[0057]-[0059], ¶[0064]-[0065], ¶[0071]-[0076]). Thus, the vessel experiences the measured distension during the corresponding acoustic-signal generation. The claim does not require the acoustic signals to cause the distension, and the rejection does not equate the distension with Reza's photoacoustically caused skin displacement.
As to determining the physiological parameter based on the physical characteristic, Wood expressly teaches determining blood pressure from the measured vessel size and calibration values representing the relationship between vessel-size change and pressure (Wood, ¶[0004], ¶[0060]-[0069], ¶[0077]-[0079]). Antonelli further corroborates determining blood-pressure information from optically measured motion over the underlying artery (Antonelli, ¶[0037]-[0038], ¶[0043]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza by configuring the stored instructions to determine vessel distension from the optically detected photoacoustic response and to determine blood pressure from that distension. A person of ordinary skill in the art would have been motivated to do so because Wood expressly acquires successive photoacoustic vessel-size measurements to capture expansion and contraction over the cardiac cycle and uses the vessel-size relationship in determining blood pressure (Wood, ¶[0060]-[0069], [0076]-[0078]). Applying that processing to Reza's displacement-encoded response therefore would have predictably provided the distension-based blood-pressure determination taught by Wood. There would have been a reasonable expectation of success because Wood demonstrates the measurement and calibration process, Reza supplies noncontact optical detection of the photoacoustic response through skin displacement, and Antonelli supports the physiological use of optically measured surface motion.
As amended, claim 19 depends from claim 18. The modified Reza teaches claim 18 as described above.
Regarding claim 19, the modified Reza teaches that the determination of a displacement of the skin of the user using a focus differential indicative of a distance to the skin, a frequency difference associated with the reflection of the continuous optical signal, a phase difference associated with the reflection of the continuous optical signal, or a combination thereof (Reza, ¶[0082]: "The reflected near-infrared beam from the sample is phase-modulated at the ultrasound frequency, and a beat-intensity can be detected", Reza expressly teaches that the reflected continuous optical signal is phase-modulated and that the resulting beat signal is detected, satisfying the phase-difference alternative; ¶[0068]: "phase (and maybe amplitude) oscillations in the probing receiver beam can be detected using interferometry", Reza further expressly teaches detection of phase oscillations in the receiver beam and independently teaches laser-Doppler detection supporting the frequency-difference alternative; ¶[0110]: Reza models the surface-reflected optical field as a function of surface displacement, further tying the detected phase of the reflected field to the displacement; ¶[0047]: Reza corroborates use of a long-coherence interrogation laser to "read-out the large local photoacoustic vibrations interferometrically").
Also regarding claim 19, Reza teaches that surface acoustic pressure produces particle velocity and displacement that phase modulates the reflected interrogation beam, and teaches noncontact optical-vibrometer measurement of displacement caused by ultrasound (Reza, ¶[0068], ¶[0081]-[0082], ¶[0109]-[0110]). Reza therefore teaches determining the photoacoustically caused skin displacement from the detected reflection, but the modified Reza does not expressly identify a vessel characteristic determined based on the displacement-encoded photoacoustic response.
Reza further provides the quantitative pressure-to-displacement relationship and digitizes the detected return at 200 MSamples/s, providing a time-resolved displacement waveform (Reza, ¶[0109], ¶[0117]). Although Reza notes a 1/ω low-pass effect, Reza states that the surface-modulation signals are readily measurable and discloses a 1 MHz to 20 MHz band-pass filter in the receiver (Reza, ¶[0109], ¶[0117]). Wood uses a 1 mm vessel-diameter scale and measures vessel size from boundary-peak timing, while Reza uses a tissue sound speed of 1500 m/s (Wood, ¶[0022], ¶[0064], ¶[0076]; Reza, ¶[0133]). Thus, a 1 mm acoustic path difference corresponds to approximately 667 ns, or a resolvable-feature rate of approximately 1.5 MHz, within Reza's disclosed detection band.
Wood teaches that pressure signals originating at the front and back vessel boundaries travel through tissue and reach the detector sequentially because of different path lengths, and that the time separation between the resulting peaks identifies vessel size (Wood, ¶[0057]-[0059]). In Reza, those propagating pressure components are transduced at the tissue surface into displacement and reflected-light phase modulation without changing their relative arrival times (Reza, ¶[0109]). Reza's time-resolved displacement waveform therefore preserves the boundary timing used in Wood's vessel-characteristic analysis. Antonelli additionally teaches extracting skin displacement from a reflected continuous optical signal and using the displacement signal in blood-pressure monitoring (Antonelli, ¶[0020], ¶[0030]-[0032], ¶[0037], ¶[0043]). The references therefore teach determining the vessel characteristic based on the displacement-encoded response without treating skin displacement itself as vessel distension.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza by configuring the stored instructions to determine the time-resolved skin-displacement waveform using Reza's phase-based optical detection and then apply Wood's vessel-boundary timing analysis to the acoustic response encoded by that displacement. A person of ordinary skill in the art would have been motivated to apply Wood's analysis because Wood teaches that temporal separation between the photoacoustic boundary responses identifies vessel dimension, while Reza's displacement signal optically represents the same time-varying photoacoustic pressure response without changing the boundary components' relative arrival times. The modification therefore would have predictably extracted the vessel characteristic taught by Wood from Reza's existing noncontact optical signal. There would have been a reasonable expectation of success because Reza supplies the quantitative pressure-to-displacement relationship and high-rate digitization, while Wood supplies and demonstrates the corresponding time-domain vessel-size processing.
Claims 8 and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Reza et al. (US-20160113507-A1), hereinafter referred to as Reza, in view of Antonelli et al. (US-20090299197-A1), hereinafter referred to as Antonelli, and further in view of Wood (US-20130109947-A1), hereinafter referred to as Wood, and Page et al. (US-20050054907-A1), hereinafter referred to as Page.
The modified Reza teaches claim 7 as described above.
Regarding claim 8, claim 8 further recites a method wherein the device comprises a wearable device, and further comprises a receiver configured to detect the reflection of the continuous optical signal. As to a receiver configured to detect the reflection of the continuous optical signal, the modified Reza expressly teaches this limitation through Reza itself (Reza, Abstract: "a detector that detects the returning portion of the interrogation beam", Reza expressly teaches a detector that receives the reflection of the CW interrogation beam from the sample, constituting a receiver configured to detect the reflection of the continuous optical signal as recited in the claim; ¶[0117]: "the reflected light back through the wave-plate creating 90° polarization which then reflects at the polarizing beam-splitter in order to guide the maximum possible intensity of reflected light to a 150 MHz-bandwidth InGaAs photodiode (PDA10CF, Thorlabs Inc., New Jersey)", Reza further expressly teaches a specific photodiode receiver configured to detect the returning reflected interrogation beam). The modified Reza does not, however, expressly teach that the device is a wearable device. Reza teaches benchtop, handheld, and endoscopic implementations, but does not disclose a body-worn device (Reza, ¶[0078]).
Page teaches "portable, non-invasive systems for blood analyte measurement integrated with a common article worn about the body" (Page, ¶[0065]) in which all measurement components including an optical source and acoustic detector are integrated within a rigid wristwatch case: "a rigid case operable for containing; a processing unit in communication with an optical source; and an acoustic detector...the bottom side suitable for supporting said acoustic detector and said optical source whereby they may be coupled to human tissue" (Page, claim 1, FIG. 5). Page further teaches that the wristwatch case "may form an enclosed space of between one and ten cubic centimeters such that the article may be easily worn about the body" (Page, ¶[0057]), and that the apparatus "is held in good and intimate contact with respect to the top of the wrist where excellent measurement may be made" (Page, ¶[0061]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza in view of Page to implement the photoacoustic measurement system in a wearable form factor. Page expressly teaches that a continuously worn device may make frequent measurements "without taking any conscious effort from the patient" and explains that a user need not manipulate or activate the system while it remains positioned for continuous measurements (Page, ¶[0031]-[0032]). A person of ordinary skill in the art would have been motivated to apply Page's wristwatch integration to the combined system to obtain frequent physiological measurements without interrupting the user's activities. There would have been a reasonable expectation of success because Reza teaches compact handheld implementations and Page demonstrates integration of a processor, optical source, detector, and associated components within a wristwatch-sized case. Page is relied upon for wearable packaging, while Reza's optical receiver remains in the combination.
Regarding claim 10, Reza teaches a user device comprising: a first light source system configured to transmit one or more first optical signals toward a target object, the one or more first optical signals configured to generate one or more acoustic signals from the target object (Reza, Abstract: "an excitation beam configured to generate ultrasonic signals in the sample at an excitation location", Reza teaches an excitation beam configured to generate ultrasonic signals in the sample, constituting a first light source system transmitting optical signals that generate acoustic signals from the target object; ¶[0046]: "Photoacoustic imaging is an emerging biomedical imaging modality that uses laser light to excite tissues. Energy absorbed by chromophores or any other absorber is converted to acoustic waves due to thermo-elastic expansion", Reza teaches that laser excitation of tissue generates acoustic waves; ¶[0047]: "at 532-nm excitation wavelength, imaging a capillary with 500 mJ/cm² local fluence would result in an initial pressure on the order of 100 MPa locally", Reza expressly teaches excitation of a capillary to generate an acoustic pressure response; ¶[0060]: "In one example, a nanosecond-pulsed laser was used" and ¶[0133]: "laser pulses should be preferably shorter than 2 µm/1500 m/s = 1.3 ns, which would require a laser with pulse widths of a nanosecond or shorter", Reza teaches pulsed laser excitation with nanosecond or shorter pulse widths); a second light source system configured to transmit a second optical signal toward a skin of the user, the skin being proximate to the target object of the user (Reza, ¶[0116]: "For the receiver arm a continuous wavelength (CW) C-band laser with 100-kHz linewidth...was used" and ¶[0114]: "Detection laser 14 may be a continuous wave laser", Reza expressly teaches that the interrogation or detection optical signal is a continuous-wave (CW) optical signal emitted by a dedicated detection laser, constituting a second light source system; Abstract: "an interrogation beam incident on the sample at the excitation location, a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals" and ¶[0049]: the acoustic signatures are interrogated using "a long-coherence length probe beam...co-focused and co-aligned with the excitation spots on sample 18", Reza teaches that the CW interrogation beam is directed toward the sample at the target location; ¶[0046]: "capable of in vivo optical-resolution photoacoustic microscopy" and ¶[0127]: "FIGS. 19a-19d depict in vivo PARS images of a mouse ear, and FIGS. 23a-23c and 24 show in vivo PARS images of a 100 g rat's ear", Reza teaches that the interrogation beam is used in vivo on the ear tissue of a living subject; ¶[0109]: "Surface pressure modulation can cause surface oscillations and the reflection of the interrogation beam from this oscillating surface can be a source of detected signal", Reza teaches that the returning portion of the interrogation beam includes reflection from the oscillating outer tissue surface; ¶[0105]: Tt is "the transmission intensity coefficient at the air-tissue interface", Reza further teaches that this surface reflection occurs at the air-tissue interface, i.e., the outer surface of the biological tissue, such that the detected returning interrogation beam includes reflection from the tissue surface previously established as the skin of the living subject; ¶[0123]: "FIG. 14a shows multifocus PARS images revealing both capillary beds and bigger blood vessels", Reza teaches that the biological tissue interrogated by the PARS system includes capillary beds and larger blood vessels underlying the interrogated surface, supporting that the interrogated skin surface is proximate to a target object comprising a blood vessel); a receiver configured to detect a reflection of the second optical signal from the skin of the user during the generation of the one or more acoustic signals, the reflection of the second optical signal indicative of a displacement of the skin of the user caused by the one or more acoustic signals generated from the target object by the one or more first optical signals, the displacement of the skin indicative of a physiological parameter of the user (Reza, Abstract: "a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals" and "a detector that detects the returning portion of the interrogation beam", Reza teaches a detector configured to receive the returning portion of the CW interrogation beam from the sample during the photoacoustic process, constituting a receiver configured to detect a reflection of the second optical signal from the skin; ¶[0047]: "large optically-focused photoacoustic signals are detected as close to the photoacoustic source as possible, which is done optically by co-focusing an interrogation beam with the excitation spot. A long-coherence length interrogation laser is preferably used with low amplitude and phase noise to read-out the large local photoacoustic vibrations interferometrically using a novel architecture designed to optimize received signal intensities", Reza teaches optical detection of local photoacoustic vibrations using the CW interrogation laser at the excitation site; ¶[0109]: "Surface pressure modulation can cause surface oscillations and the reflection of the interrogation beam from this oscillating surface can be a source of detected signal", Reza teaches detecting the reflection of the CW interrogation beam from the tissue surface during acoustic signal generation).
Reza teaches that the reflection is indicative of the photoacoustically caused surface displacement. Reza states that acoustic signals propagating to the tissue surface produce phase modulation of reflected light, that surface pressure modulation causes surface oscillations, and that reflection from the oscillating surface provides the detected signal (Reza, ¶[0109]). Reza also models the reflected optical field as a function of the surface displacement and teaches interferometric or laser-Doppler vibrometer detection of that displacement (Reza, ¶[0068], ¶[0081]-[0082], ¶[0110]). These disclosures establish that the detected reflection is modulated by, and therefore carries information representing, the photoacoustically caused surface displacement. Reza does not expressly state that a processor determines a displacement value from the reflection. Claim 10, however, requires only "the reflection of the second optical signal indicative of a displacement of the skin of the user caused by the one or more acoustic signals generated from the target object by the one or more first optical signals." Claim 10 does not recite that separate determining step.
Also regarding claim 10, Reza does not expressly teach that the displacement of the skin indicated by the detected reflection of the second optical signal is indicative of a physiological parameter of the user. Reza discloses processing of the returning interrogation beam to form images and to detect photoacoustic signals (Reza, ¶[0018]), but does not expressly disclose determining a physiological parameter such as blood pressure based on the determined photoacoustic skin displacement.
Antonelli expressly teaches this limitation. Antonelli teaches a "non-contact method and apparatus for continuously monitoring physiological events such as the anatomical blood pressure waveform" (Antonelli, ¶[0028]). Antonelli teaches directing a continuous-wave laser beam toward the skin over an artery and detecting the reflected beam: "[a] low-power (1 mW), continuous, red laser beam is directed onto the measurement surface. By interfering the detected beam that was reflected by the measurement surface with a reference beam within the LDV, a measure of the surface velocity is obtained" (Antonelli, ¶[0019]). Antonelli further teaches that the signal processor derives blood pressure waveform information from the detected reflected beam: "The computer can be calibrated to correlate the velocity and motion of the skin surface to the pressure of the blood in the artery beneath skin surface" (Antonelli, ¶[0037]), and that "[u]tilizing the pulsation velocity of skin surface over time, computer can plot a highly accurate representative blood pulse waveform" (Antonelli, ¶[0038]). Antonelli therefore expressly teaches that a reflected CW optical signal from the skin over an artery is processed to derive blood pressure waveform information, establishing that such a reflected signal is indicative of a physiological parameter of the user.
Wood further teaches that pressure signals from the front and back vessel boundaries travel through tissue and arrive sequentially because of their different path lengths, and that the resulting peak timing identifies vessel size used to determine blood pressure (Wood, ¶[0057]-[0069], ¶[0074]-[0078]). Reza independently teaches that arriving surface pressure produces displacement that phase modulates the reflected interrogation beam and digitizes the return at 200 MSamples/s (Reza, ¶[0109], ¶[0117]). Although Reza notes a 1/ω low-pass effect, Reza states that the surface-modulation signals are readily measurable and discloses a 1 MHz to 20 MHz band-pass filter in the receiver (Reza, ¶[0109], ¶[0117]). Wood uses a 1 mm vessel-diameter scale and measures vessel size from boundary-peak timing, while Reza uses a tissue sound speed of 1500 m/s (Wood, ¶[0022], ¶[0064], ¶[0076]; Reza, ¶[0133]). Thus, a 1 mm acoustic path difference corresponds to approximately 667 ns, or a resolvable-feature rate of approximately 1.5 MHz, within Reza's disclosed detection band. Reza's surface transduction therefore preserves the boundary components' relative arrival times, and Wood establishes that the time-resolved displacement-encoded photoacoustic response detected by Reza is indicative of a physiological parameter.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Reza in view of Antonelli and Wood such that the displacement indicated by the detected reflection is indicative of blood pressure and, to the extent necessary, the noncontact interrogation is applied to human skin over a target blood vessel. A person of ordinary skill in the art would have been motivated to employ Antonelli's human-skin measurement arrangement because Antonelli teaches that reflected-light measurement of skin displacement over an artery permits noninvasive acquisition of cardiovascular information from an accessible skin surface (Antonelli, ¶[0019]-[0020], [0037], [0043]). A person of ordinary skill in the art would separately have been motivated to apply Wood's processing because Wood teaches that the temporal separation between photoacoustic responses from opposing vessel boundaries provides the vessel dimension used to determine blood pressure (Wood, ¶[0057]-[0069], [0074]-[0078]). Reza's detected surface displacement represents that same time-varying photoacoustic response, and Reza's receiver preserves the boundary timing used by Wood. The modifications therefore would have predictably made the displacement indicated by Reza's reflection indicative of the blood-pressure information Wood derives, while using Antonelli's established human-skin measurement location. There would have been a reasonable expectation of success because Reza's receiver passes the timing information used by Wood, Wood demonstrates its photoacoustic blood-pressure method, and Antonelli demonstrates reflected-light measurement of blood-pressure-related human-skin motion.
Also regarding claim 10, the modified Reza does not expressly teach a wearable structure securable to the user and comprising the first light source system, the second light source system, and the receiver. Reza teaches benchtop, handheld, and endoscopic implementations, but does not disclose integration into a body-worn device (Reza, ¶[0078]).
Page teaches a "portable, non-invasive system for blood analyte measurement integrated with a common article worn about the body" (Page, ¶[0065]) in which all measurement components including an optical source and acoustic detector are integrated within a rigid wristwatch case: "a rigid case operable for containing; a processing unit in communication with an optical source; and an acoustic detector...the bottom side suitable for supporting said acoustic detector and said optical source whereby they may be coupled to human tissue" (Page, claim 1, FIG. 5). Page further teaches that the wristwatch case "may form an enclosed space of between one and ten cubic centimeters such that the article may be easily worn about the body" (Page, ¶[0057]), and that the apparatus "is held in good and intimate contact with respect to the top of the wrist where excellent measurement may be made" (Page, ¶[0061]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza in view of Page to provide a wearable structure containing the first light source system, second light source system, and Reza's receiver. Page expressly teaches that a continuously worn device may make frequent measurements "without taking any conscious effort from the patient" and explains that a user need not manipulate or activate the system while it remains positioned for continuous measurements (Page, ¶[0031]-[0032]). A person of ordinary skill in the art would have been motivated to apply Page's wristwatch integration to obtain frequent physiological measurements without interrupting the user's activities. There would have been a reasonable expectation of success because Reza teaches compact handheld implementations and Page demonstrates integration of photoacoustic source, detector, processor, and associated components within a wristwatch-sized case. Page is relied upon only for the wearable packaging; Reza's optical receiver remains the receiver of the combined device.
Regarding claim 11, claim 11 further recites a control system, the control system configured to: determine a physical characteristic of the target object based at least on the reflection of the second optical signal; and determine the physiological parameter of the user based on the physical characteristic of the target object. Reza teaches that the reflected interrogation beam encodes the photoacoustic response and that a processor calculates information about the sample from the returning beam (Reza, ¶[0018], ¶[0109]).
Reza does not expressly identify a discrete target-object characteristic as the intermediate basis for the physiological-parameter determination.
Wood expressly teaches both steps in the photoacoustic context. Wood determines vessel size or diameter from boundary peaks in the photoacoustic response and then determines blood pressure from the measured vessel size and calibration values (Wood, ¶[0057]-[0069], ¶[0074]-[0078]). Antonelli additionally teaches extracting skin displacement from the reflected optical signal and correlating the surface motion to pressure in the underlying artery (Antonelli, ¶[0020], ¶[0037], ¶[0043]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza by configuring the control system to apply Wood's disclosed processing to Reza's optically detected photoacoustic response, thereby determining vessel size or diameter as the target-object characteristic and determining blood pressure from that characteristic. A person of ordinary skill in the art would have been motivated to select vessel size or diameter because Wood expressly identifies that characteristic from the temporal separation of the photoacoustic boundary responses and uses it as the measured intermediate in its blood-pressure determination (Wood, ¶[0057]-[0069], [0074]-[0078]). Applying Wood's processing to Reza's displacement-encoded response therefore would have predictably obtained the same physiologically relevant intermediate taught by Wood. There would have been a reasonable expectation of success based on Wood's demonstrated method and Reza's existing processor, while Antonelli further confirms that an optical displacement signal over a vessel is suitable for blood-pressure monitoring.
Regarding claim 12, claim 12 further recites a device wherein the physical characteristic of the target object comprises a distension experienced by the target object during the generation of the one or more acoustic signals, and the physiological parameter comprises blood pressure of the user. The combined Reza, Antonelli, and Wood system teaches vessel size or diameter as the physical characteristic and blood pressure as the physiological parameter as described regarding claim 11.
Wood expressly teaches blood pressure as the physiological parameter and determines blood pressure from the measured vessel size and calibration values (Wood, ¶[0004], ¶[0067]-[0069], ¶[0077]-[0078]). Antonelli also teaches correlating optically measured skin motion to pressure in the underlying artery (Antonelli, ¶[0037]-[0038], ¶[0043]).
Wood expressly teaches vessel distension. Wood identifies distensibility as the vessel's ability to stretch in response to blood-pressure changes, defines it using change in vessel volume, and teaches photoacoustic measurements that capture expansion and contraction over the cardiac cycle (Wood, ¶[0003], ¶[0060]-[0065]). Each photoacoustic measurement generates an acoustic signal while the vessel occupies a particular expanded or contracted state. The vessel therefore experiences the recited distension during acoustic-signal generation. The acoustic signal is not asserted to cause the distension.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza by configuring the control system to repeatedly apply Wood's vessel-size processing to Reza's optically detected photoacoustic response over the cardiac cycle and to determine blood pressure from the resulting vessel distension. A person of ordinary skill in the art would have been motivated to do so because Wood expressly monitors expansion and contraction through successive photoacoustic vessel-size measurements and uses the resulting vessel-size relationship in its pressure calibration (Wood, ¶[0060]-[0069], [0076]-[0078]). The modification therefore would have predictably produced the distension measurement and blood-pressure determination taught by Wood. There would have been a reasonable expectation of success based on Wood's demonstrated measurement and calibration process, while Antonelli further supports the clinical utility of noncontact optical monitoring of vessel-associated motion.
Regarding claim 13, claim 13 further recites a device wherein the determination of the physical characteristic of the target object comprises determination of a displacement of the skin of the user, the physical characteristic of the target object determined based on the displacement of the skin. Reza teaches that the reflected second optical signal is modulated by, and carries information representing, the photoacoustically caused skin displacement (Reza, ¶[0068], ¶[0081]-[0082], ¶[0109]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza to determine a displacement value from the detected phase modulation, to the extent such a determination is required, for the reasons set forth regarding claim 1.
Wood teaches that pressure signals from the front and back vessel boundaries travel through tissue and arrive sequentially because of their different path lengths, and that the time separation of the resulting peaks identifies vessel diameter (Wood, ¶[0057]-[0059]). Reza teaches that the arriving surface pressure produces displacement that phase modulates the reflected interrogation beam and that the return is digitized at 200 MSamples/s (Reza, ¶[0068], ¶[0081]-[0082], ¶[0109], ¶[0117]). The surface-displacement transduction therefore preserves the relative boundary arrival times in a time-resolved optical waveform from which Wood's target-object size may be determined. Antonelli additionally teaches extracting skin displacement from a reflected continuous optical signal and using the displacement signal for blood-pressure monitoring (Antonelli, ¶[0020], ¶[0030]-[0032], ¶[0037], ¶[0043]). The references collectively teach determining the displacement first and determining the target-object characteristic based on the displacement-encoded response.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza by configuring the control system to determine Reza's time-resolved displacement signal and apply Wood's vessel-boundary timing analysis to the photoacoustic response encoded by that signal. A person of ordinary skill in the art would have been motivated to apply Wood's analysis because Reza's displacement signal represents the time-varying photoacoustic pressure response, while Wood teaches extracting vessel dimension from the timing structure of that response. Reza's surface-displacement transduction preserves the relative boundary arrival times and its receiver digitizes the relevant timing information. The modification therefore would have predictably determined Wood's target-object characteristic from Reza's existing noncontact optical signal. There would have been a reasonable expectation of success because Reza supplies a quantitative pressure-to-displacement relationship and high-rate digitization, Wood demonstrates the time-domain vessel-size analysis, and Antonelli demonstrates reflected-light displacement extraction.
Regarding claim 14, the modified Reza teaches that the determination of the displacement of the skin of the user is based on a focus differential indicative of a distance to the skin, a change in frequency associated with the reflection of the second optical signal, a phase difference associated with the reflection of the second optical signal, or a combination thereof (Reza, ¶[0082]: "The reflected near-infrared beam from the sample is phase-modulated at the ultrasound frequency, and a beat-intensity can be detected", Reza expressly teaches that the reflected interrogation beam is phase-modulated and that the resulting beat signal is detected, satisfying the phase-difference alternative; ¶[0068]: "phase (and maybe amplitude) oscillations in the probing receiver beam can be detected using interferometry", Reza further expressly teaches detection of phase oscillations in the receiver beam and independently teaches laser-Doppler detection supporting the frequency-difference alternative; ¶[0110]: Reza models the surface-reflected optical field as a function of surface displacement, further tying the detected phase of the reflected field to the displacement; ¶[0047]: Reza corroborates use of a long-coherence interrogation laser to "read-out the large local photoacoustic vibrations interferometrically").
Regarding claim 15, the modified Reza teaches that the target object comprises a blood vessel of the user (Reza, ¶[0047]: "at 532-nm excitation wavelength, imaging a capillary with 500 mJ/cm² local fluence would result in an initial pressure on the order of 100 MPa locally", Reza expressly teaches that the target object excited by the pulsed optical signals is a capillary, i.e., a blood vessel of the subject; ¶[0123]: "FIG. 14a shows multifocus PARS images revealing both capillary beds and bigger blood vessels", Reza further teaches that the PARS system images both capillary beds and larger blood vessels as the target objects of the system; ¶[0004]: "Photoacoustic microscopy has shown significant potential for imaging vascular structures from macro-vessels all the way down to micro-vessels", Reza expressly identifies vascular structures, i.e., blood vessels of a subject, as the target objects for photoacoustic interrogation; ¶[0127]: "FIGS. 19a-19d depict in vivo PARS images of a mouse ear, and FIGS. 23a-23c and 24 show in vivo PARS images of a 100 g rat's ear", Reza teaches that the target objects are blood vessels of a living subject imaged in vivo); the one or more first optical signals comprise pulsed laser signals (Reza, ¶[0060]: "In one example, a nanosecond-pulsed laser was used", Reza expressly teaches a pulsed laser as the source of the excitation optical signals directed toward the target object; ¶[0114]: "a 1 ns pulse width, frequency doubled ytterbium-doped fiber laser (IPG Photonics Inc.) with a pulse repetition rate (PRR) of 40 kHz", Reza further expressly teaches a specific pulsed laser used as the first optical signal source; ¶[0133]: "laser pulses should be preferably shorter than 2 µm/1500 m/s = 1.3 ns, which would require a laser with pulse widths of a nanosecond or shorter", Reza confirms that the first optical signals are pulsed laser signals with nanosecond-scale pulse durations as recited in the claim); the second optical signal comprises a continuous laser signal (Reza, ¶[0114]: "Detection laser 14 may be a continuous wave laser", Reza expressly teaches that the detection or interrogation optical signal is emitted by a continuous wave laser, constituting a continuous laser signal as recited in the claim; ¶[0116]: "For the receiver arm a continuous wavelength (CW) C-band laser with 100-kHz linewidth (TLK-L1550R, Thorlabs Inc., New Jersey) was used", Reza further expressly teaches a specific CW laser as the source of the second optical signal); the receiver comprises a photodetector configured to determine a frequency or a phase of the reflection of the continuous laser signal while the pulsed laser signals are transmitted toward the target object of the user (Reza, ¶[0117]: "the reflected light back through the wave-plate creating 90° polarization which then reflects at the polarizing beam-splitter in order to guide the maximum possible intensity of reflected light to a 150 MHz-bandwidth InGaAs photodiode (PDA10CF, Thorlabs Inc., New Jersey)", Reza expressly teaches that the receiver is a photodetector, specifically an InGaAs photodiode, that receives the reflection of the CW interrogation laser signal from the sample; ¶[0082]: "The reflected near-infrared beam from the sample is phase-modulated at the ultrasound frequency, and a beat-intensity can be detected", Reza expressly teaches determining phase modulation associated with the reflected continuous laser signal; ¶[0068]: "phase (and maybe amplitude) oscillations in the probing receiver beam can be detected using interferometry", Reza further expressly teaches interferometric detection of phase oscillations in the receiver beam and independently teaches laser-Doppler detection supporting the frequency alternative; ¶[0110]: Reza models the surface-reflected optical field as a function of surface displacement, further tying the detected phase of the reflected field to the displacement; ¶[0047]: Reza corroborates use of a long-coherence interrogation laser to "read-out the large local photoacoustic vibrations interferometrically").
Regarding claim 16, the modified Reza teaches that the displacement of the skin determined based on a focus differential indicative of a distance to the skin, a difference in the frequency associated with the reflection of the continuous laser signal, a phase difference associated with the reflection of the continuous laser signal, or a combination thereof (Reza, ¶[0082]: "The reflected near-infrared beam from the sample is phase-modulated at the ultrasound frequency, and a beat-intensity can be detected", Reza expressly teaches that the reflected interrogation beam is phase-modulated and that the resulting beat signal is detected, satisfying the phase-difference alternative; ¶[0068]: "phase (and maybe amplitude) oscillations in the probing receiver beam can be detected using interferometry", Reza further expressly teaches detection of phase oscillations in the receiver beam and independently teaches laser-Doppler detection supporting the frequency-difference alternative; ¶[0110]: Reza models the surface-reflected optical field as a function of surface displacement, further tying the detected phase of the reflected field to the displacement; ¶[0047]: Reza corroborates use of a long-coherence interrogation laser to "read-out the large local photoacoustic vibrations interferometrically").
Also regarding claim 16, with respect to the device further comprising a control system configured to determine the physiological parameter of the user based on a displacement of the skin during the generation of the one or more acoustic signals, Reza teaches that surface pressure modulation causes surface oscillations that modulate the reflected interrogation beam and teaches noncontact measurement of displacement caused by ultrasound signals (Reza, ¶[0057], ¶[0109]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza to determine a displacement value from the detected phase modulation, to the extent such a determination is required, for the reasons set forth regarding claim 1. Reza does not expressly determine the physiological parameter from the displacement.
Wood teaches that the photoacoustic response represented by Reza's measured displacement contains vessel-size information and that blood pressure is determined from the measured vessel size and calibration values (Wood, ¶[0057]-[0069], ¶[0074]-[0078]). Antonelli additionally teaches extracting skin displacement from the detected continuous-wave reflection and correlating the surface motion to pressure in the underlying artery (Antonelli, ¶[0020], ¶[0037], ¶[0043]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza by configuring the control system to determine blood pressure from the displacement-encoded photoacoustic response using Wood's vessel-characteristic and calibration processing. A person of ordinary skill in the art would have been motivated to apply Wood's processing because Wood expressly uses the photoacoustic response to determine vessel size and blood pressure, while Reza's optically measured displacement represents that response. Applying Wood's analysis to Reza's displacement-encoded response therefore would have predictably determined the physiological information Wood teaches is contained in the response. There would have been a reasonable expectation of success because Wood demonstrates the vessel-size and blood-pressure processing, Reza provides a time-resolved optical representation of the photoacoustic response, and Antonelli confirms the physiological use of reflected-light skin displacement over a vessel.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Reza et al. (US-20160113507-A1), hereinafter referred to as Reza, in view of Antonelli et al. (US-20090299197-A1), hereinafter referred to as Antonelli, and further in view of Wood (US-20130109947-A1), hereinafter referred to as Wood, and Ruan et al. (US-20190336007-A1), hereinafter referred to as Ruan.
The modified Reza teaches claim 7 as described above.
Regarding claim 9, the modified Reza teaches a method wherein the continuous optical signal has a wavelength of up to 1550 nm, and wherein the pulsed optical signals have a wavelength in the range of 450-850 nm and a duration of up to 500 ns (Reza, ¶[0116]: "For the receiver arm a continuous wavelength (CW) C-band laser with 100-kHz linewidth (TLK-L1550R, Thorlabs Inc., New Jersey) was used", Reza expressly teaches a CW interrogation laser operating at 1550 nm, directly within the recited wavelength of up to 1550 nm; ¶[0134]: "A wavelength of 1550 nm may be used with a 532 nm excitation light because it is spectrally different...and because it is a key band in optical communications where a plethora of components are available", Reza further confirms 1550 nm as the interrogation wavelength and provides the rationale for that selection, establishing the recited CW wavelength limitation; ¶[0047]: "at 532-nm excitation wavelength, imaging a capillary with 500 mJ/cm² local fluence would result in an initial pressure on the order of 100 MPa locally", Reza expressly teaches a 532 nm pulsed excitation source, squarely within the recited pulsed wavelength range of 450-850 nm; ¶[0114]: "a 1 ns pulse width, frequency doubled ytterbium-doped fiber laser (IPG Photonics Inc.) with a pulse repetition rate (PRR) of 40 kHz", Reza expressly teaches 1 ns pulsed laser operation, well within the recited pulsed duration of up to 500 ns; ¶[0133]: "laser pulses should be preferably shorter than 2 µm/1500 m/s = 1.3 ns , which would require a laser with pulse widths of a nanosecond or shorter", Reza further confirms that nanosecond-scale pulse durations satisfy the stress confinement requirements of the photoacoustic technique, establishing the recited pulsed duration limitation).
Also regarding claim 9, the modified Reza does not expressly teach a method wherein the continuous optical signal has a duration of up to 10 microseconds. Rather, the modified Reza discloses a truly continuous wave interrogation laser with no stated gating, windowing, or bounded measurement period applied to the CW beam itself.
Ruan teaches more than detecting a return during a bounded acquisition period. Ruan expressly describes an "optical source configured for generating source light during each of at least one measurement period" and states that each period is preferably "equal to or less than 10 microseconds" (Ruan, ¶[0030]). Ruan further teaches that the controller instructs the optical source, that the source sweep rate defines the measurement period, and that the source generates the source-light sweep during that period (Ruan, ¶[0077]-[0079], ¶[0135]). Ruan therefore expressly associates generation of the source optical signal with a controller-defined period of up to 10 microseconds, rather than merely limiting post-detection processing to that interval.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza in view of Ruan so that Reza's continuous-wave interrogation signal is generated over a controller-defined measurement duration of up to 10 microseconds. Reza identifies long-coherence-length, low-amplitude-noise, and low-phase-noise interrogation as important to interferometric readout (Reza, ¶[0047], ¶[0068]). Ruan identifies the more precise tissue-motion mechanism limiting that readout: the measurement should be completed before the tissue speckle pattern decorrelates, and preferably within 10 microseconds (Ruan, ¶[0013], ¶[0079], ¶[0120]). A person of ordinary skill in the art would therefore have been motivated to use Ruan's controller-defined source period in Reza to preserve phase and amplitude stability and improve interferometric signal fidelity. Ruan's express speckle-decorrelation teaching provides the physical basis for the same signal-fidelity and coherence objective identified by Reza. There would have been a reasonable expectation of success because Ruan expressly controls source-light generation during the bounded period and Reza already digitizes the resulting optical return. The laser remains a continuous-wave source because its optical output is continuous within each bounded interrogation interval; bounding the interval does not make it the nanosecond pulsed excitation source.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Reza et al. (US-20160113507-A1), hereinafter referred to as Reza, in view of Antonelli et al. (US-20090299197-A1), hereinafter referred to as Antonelli, and further in view of Wood (US-20130109947-A1), hereinafter referred to as Wood, and Ruan et al. (US-20190336007-A1), hereinafter referred to as Ruan.
The modified Reza teaches claim 17 as described above.
Regarding claim 20, the modified Reza teaches a non-transitory computer-readable apparatus wherein: the continuous optical signal comprises a continuous optical signal emitted by a second light source, wherein the continuous optical signal emitted by the second light source comprises an optical signal having a wavelength of up to 1550 nm generated by a second laser (Reza, ¶[0116]: "For the receiver arm a continuous wavelength (CW) C-band laser with 100-kHz linewidth (TLK-L1550R, Thorlabs Inc., New Jersey) was used", Reza expressly teaches a CW laser operating at 1550 nm as the second light source, directly within the recited wavelength of up to 1550 nm; ¶[0134]: "A wavelength of 1550 nm may be used with a 532 nm excitation light because it is spectrally different...and because it is a key band in optical communications where a plethora of components are available", Reza further confirms 1550 nm as the interrogation wavelength and provides the rationale for that selection, establishing the recited CW wavelength limitation; ¶[0114]: "Detection laser 14 may be a continuous wave laser", Reza expressly teaches that the second light source is a dedicated continuous wave laser, constituting the second laser as recited in the claim); the one or more pulsed optical signals comprise one or more optical signals emitted by a first light source, wherein the one or more pulsed optical signals emitted by the first light source comprise one or more optical signals having a wavelength of 450-850 nm each generated by a first laser configured to obtain a photoacoustic response from the blood vessel over a second duration up to 500 nanoseconds during the first duration (Reza, ¶[0047]: "at 532-nm excitation wavelength, imaging a capillary with 500 mJ/cm² local fluence would result in an initial pressure on the order of 100 MPa locally", Reza expressly teaches a 532 nm pulsed excitation source, squarely within the recited pulsed wavelength range of 450-850 nm; ¶[0046]: "Energy absorbed by chromophores or any other absorber is converted to acoustic waves due to thermo-elastic expansion", Reza teaches that the pulsed excitation laser is configured to obtain a photoacoustic response from the biological target, i.e., a blood vessel, as recited in the claim; ¶[0114]: "a 1 ns pulse width, frequency doubled ytterbium-doped fiber laser (IPG Photonics Inc.) with a pulse repetition rate (PRR) of 40 kHz", Reza expressly teaches 1 ns pulsed laser operation, well within the recited second duration of up to 500 nanoseconds; ¶[0133]: "laser pulses should be preferably shorter than 2 µm/1500 m/s = 1.3 ns, which would require a laser with pulse widths of a nanosecond or shorter", Reza further confirms that nanosecond-scale pulse durations satisfy the stress confinement requirements of the photoacoustic technique, establishing the recited pulsed duration limitation); the first light source and the second light source are disposed at different locations of a device (Reza, ¶[0114] and FIG. 20: Reza depicts the experimental PARS system in FIG. 20, showing pulsed laser 12 and detection laser 14 as entirely separate, spatially distinct components within the system architecture, with their respective beams combined only downstream at dual beam combiner 2218 before reaching the sample, expressly teaching that the first and second light sources occupy different locations within the device; ¶[0118] and FIG. 22: Reza further depicts in FIG. 22 an alternative system configuration in which pulse laser 12 provides an additional beam to polarization maintaining single mode fiber 2402, lens system 42, and then to beam combiner unit 30, while continuous wave lasers 2404 and 2406 provide separate beams that are likewise combined at beam combiner unit 30 before reaching sample 18, again expressly teaching two light sources disposed at different locations within the device as recited in the claim).
Also regarding claim 20, the modified Reza does not expressly teach that the continuous optical signal is generated by the second laser over a first duration up to 10 microseconds. Rather, the modified Reza discloses a truly continuous wave interrogation laser with no stated gating, windowing, or bounded measurement period applied to the CW beam itself.
Ruan expressly teaches controller-governed generation of source light during the recited interval. Ruan describes an "optical source configured for generating source light during each of at least one measurement period" and provides that each period is preferably "equal to or less than 10 microseconds" (Ruan, ¶[0030]). Ruan further teaches that the controller instructs the optical source, that the source sweep rate defines the measurement period, and that the controller sends a control signal to the source drive circuit to generate the source-light sweep during each period (Ruan, ¶[0077]-[0079], ¶[0135]). Ruan thus expressly ties source-light generation, not merely detection or later processing, to a first duration of up to 10 microseconds.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Reza in view of Ruan by configuring the stored instructions to cause the second laser to generate Reza's continuous-wave interrogation signal over a controller-defined first duration of up to 10 microseconds. Reza identifies long-coherence-length, low-amplitude-noise, and low-phase-noise interrogation as important to interferometric readout (Reza, ¶[0047], ¶[0068]). Ruan identifies the precise tissue-motion mechanism limiting that readout by teaching completion of the source-light measurement before tissue speckle decorrelation, preferably within 10 microseconds (Ruan, ¶[0013], ¶[0030], ¶[0079], ¶[0120]). A person of ordinary skill in the art would have been motivated to implement Ruan's controller-defined source period in the stored instructions to preserve phase and amplitude stability and thereby improve the fidelity of each photoacoustic measurement. Ruan's speckle-decorrelation teaching supplies the physical basis for preserving interferometric coherence and signal quality during the interrogation window. There would have been a reasonable expectation of success because Ruan expressly controls the source drive circuit and generates source light during each bounded period, while Reza already controls and digitizes the optical interrogation return. The second laser remains a continuous-wave laser because its output is continuous within the bounded first duration; it is not converted into the nanosecond pulsed excitation laser.
Response to Arguments
Objections
Applicant's arguments filed 7/9/2026, page 10, regarding the previous Objections of claim 10 have been fully considered and are persuasive. The previous Objections have been withdrawn. However, there is a new objection as shown above.
35 U.S.C. §112(b)
Applicant's arguments filed 7/9/2026, page 10, regarding the previous 112(b) Rejections of claim 19 have been fully considered and are persuasive. The previous 112(b) rejections have been withdrawn.
35 U.S.C. §103
Applicant's arguments filed 7/9/2026, pages 10-12, regarding the previous 103 Rejections of claims 1-20 have been fully considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. That is, there are new grounds of rejection.
Applicant's Argument: Applicant argues that amended claims 1, 10, and 17 require a specific causal chain in which pulsed optical signals generate acoustic signals from a blood vessel or target object, those acoustic signals cause displacement of the skin, the displacement is determined from the reflected continuous optical signal, and a physiological parameter is determined from the displacement. Applicant argues that the prior Reza and Antonelli combination does not teach the complete causal chain and that the dependent claims are allowable by virtue of their dependency.
Examiner's Response: Applicant's arguments are moot to the extent they are directed to the prior grounds of rejection, which have been withdrawn and superseded by new grounds necessitated by the amendments. The current rejection applies Reza, Antonelli, and newly cited Wood to claims 1-7 and 17-19; Reza, Antonelli, Wood, and Page to claims 8 and 10-16; and Reza, Antonelli, Wood, and Ruan to claims 9 and 20. The current theory does not rely on Antonelli alone to bridge Reza's photoacoustic signal to the physiological parameter. Wood supplies the photoacoustically matched relationship between the detected response, vessel dimensions or distension, and blood pressure. The amendment expressly requiring photoacoustically caused skin displacement necessitated this new combination and reassessment of every claim that incorporates the amended subject matter. Page retains its prior role of supplying wearable integration for claims 8 and 10-16, and Ruan retains its prior role of supplying the bounded 10-microsecond optical-signal duration for claims 9 and 20. The additional explanations clarify the existing applications of Page and Ruan without changing either reference’s role in the stated grounds of rejection.
Applicant's Argument: Applicant argues more specifically that Reza forms images but does not determine skin displacement caused by the acoustic signal, and that Reza's references to a red blood cell concern cells rather than the claimed skin.
Examiner's Response: The argument is not persuasive. The isolated red blood cell in Reza is the exemplary subsurface photoacoustic source, not the surface being measured. Reza separately and expressly teaches that 532 nm excitation of a capillary generates an initial acoustic pressure response (Reza, ¶[0047]). Reza states that acoustic signals propagate to the tissue surface, cause surface oscillation, and phase modulate reflected interrogation light; Reza also supplies the quantitative pressure-to-displacement relationship and models the reflected optical field as a function of surface displacement (Reza, ¶[0109]-[0110]). Reza further teaches interferometric or laser-Doppler detection and identifies PARS as an optical vibrometer for noncontact displacement measurement (Reza, ¶[0068], ¶[0081]-[0082]). Thus, even if Reza does not expressly state in a single blood-vessel embodiment that its processor outputs a numerical displacement value, it would have been obvious to use Reza's disclosed relationship and optical-vibrometer processing to determine displacement from the detected phase modulation for the reasons set forth in the rejection. Reza also expressly teaches noncontact in vivo photoacoustic microscopy at an air-tissue interface and demonstrates in vivo ear imaging over vascular structures (Reza, ¶[0046], ¶[0105], ¶[0123], ¶[0127]). To the extent those examples do not expressly identify human skin, Antonelli teaches applying reflected-light displacement measurement to human skin over an artery (Antonelli, ¶[0019]-[0020], ¶[0037], ¶[0043]).
Applicant's Argument: Applicant argues that Antonelli's displacement is caused by passive cardiac pulsation rather than by photoacoustic signals, that the prior references do not bridge the two physical phenomena, and that the dependent claims are allowable for the same reason.
Examiner's Response: Applicant's argument addresses Antonelli individually for a teaching Antonelli is not relied upon to supply. Nonobviousness cannot be established by attacking references individually where the rejection rests on their combined teachings. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Reza supplies the photoacoustic source-to-surface-displacement path and, at minimum, renders determination of displacement from the reflected phase modulation obvious for the reasons discussed above. Wood teaches that pressure signals from the vessel boundaries travel through tissue with different arrival times and that the resulting photoacoustic response contains vessel-size information from which blood pressure is determined (Wood, ¶[0057]-[0069], ¶[0074]-[0078]). Antonelli is relied upon for the narrower corroborating teaching that reflected-light measurement of skin displacement over a vessel is a usable physiological signal (Antonelli, ¶[0019]-[0020], ¶[0037], ¶[0043]). The rejection does not rely on Antonelli's passive cardiac displacement as the cause of Reza's photoacoustically generated displacement and does not equate skin displacement with vessel distension. Claims 2, 3, 5, 11-13, 16, 18, and 19 are specifically reassessed under the new Reza, Antonelli, and Wood base combination, and the remaining dependent-claim limitations are taught or suggested for the claim-specific reasons set forth above. Applicant has not separately traversed those additional limitations.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/AARON MERRIAM/Examiner, Art Unit 3791
/MATTHEW KREMER/Primary Examiner, Art Unit 3791
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