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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Regarding claim 8, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). for examination purposes, the terms “”on” state” and “”off” state” would not be considered as required parts of the claimed invention.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-12, 14-27 and 29-32 are rejected under 35 U.S.C. 103 as being unpatentable over Stone (US 20190277766 A1) in view of Kawamura (US 20120029326 A1).
Regarding claim 1, Stone teaches a method of detecting one or more properties of a sub-surface volume of a diffusely scattering sample which comprises surface enhanced Raman Spectroscopy (SERS) probes, the SERS probes being spectrally responsive to a stimulus (Abstract, [0054]), the method comprising:
during the stimulus, directing probe light to an entry region on a surface of the sample, and collecting a portion of the probe light, including elements of said probe light Raman scattered from said SERS probes, at a collection region on the surface of the sample, the collection region being spaced from the entry region ([0041]);
measuring the collected Raman scattered elements ([0042]); but fails to disclose providing the stimulus in a varying form at the sub-surface volume;
detecting variations in the measured Raman scattered elements which are induced by the variations in the stimulus; and
detecting the one or more properties based on the detected variations in the measured Raman scattered elements.
However, Kawamura, from the same field of endeavor, teaches providing the stimulus in a varying form at the sub-surface volume ([0079]-[0080] the stimulus is the polarization direction of light, A projection module 21 modulates the polarization direction of the linear-polarized light 5);
detecting variations in the measured Raman scattered elements which are induced by the variations in the stimulus ([0079] the intensity of the surface enhanced Raman scattering light is varied depending on modulation of the polarization direction of the liner-polarized light, [0084] A lock-in amplifier 16 uses the modulation signal as a reference signal to perform phase detection of the output signal from the light sensor 14); and detecting the one or more properties (concentration) based on the detected variations in the measured Raman scattered elements ([0084] A computer 17 calculates a concentration of the biogenic substance on the basis of the output signal of the lock-in amplifier 16 to control the signal generator 15).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Stone by incorporating providing the stimulus in a varying form at the sub-surface volume; detecting variations in the measured Raman scattered elements which are induced by the variations in the stimulus; and detecting the one or more properties based on the detected variations in the measured Raman scattered elements in order to improve measurement accuracy ([0046]).
Regarding claim 2, Stone, when modified by Kawamura, the method of claim 1, wherein the variations in the stimulus comprise changes in the stimulus over time at the sub-surface volume, and the variations in the measured Raman scattered elements which are induced by the variations in the stimulus comprise changes in the measured Raman scattered elements over time (Kawamura: [0086] polarized light 5 is modulated continuously).
Regarding claim 3, Stone, when modified by Kawamura, the method of claim 1, wherein detecting the variations in the measured Raman scattered elements which are induced by variations in the stimulus comprises detecting such variations that are in synchrony with, or are correlated with, the variations in the stimulus (Kawamura: [0079], [0084]).
Regarding claim 4, Stone, when modified by Kawamura, the method of claim 1, wherein the variations in the measured Raman scattered elements induced by variations in the stimulus comprise variations in one or more of: the spectral shape or form, the intensity or relative intensity, the width, and the wavenumber, of one or more Raman spectral features of the measured Raman scattered elements (Kawamura: intensity, [0086], [0092]).
Regarding claim 5, Stone, when modified by Kawamura, teaches the method of claim 1, wherein the step of detecting the one or more properties comprises forming a component spectrum (Amplitude Am) representing variations in the measured Raman scattered elements induced by variations in the stimulus, and determining the one or more properties from the component spectrum (Kawamura: [0037] calculating the concentration of the biological substance from the Am)
Regarding claim 6, Stone, when modified by Kawamura, teaches the method of claim 5, wherein the component spectrum is a principal component of the measured Raman scattered elements, formed using principal component analysis, or a partial least squares component of the measured Raman scattered elements, formed using partial least squares analysis, the principal or partial least squares component representing changes in the measured Raman scattered elements which are induced by changes in the varying stimulus (Stone: [0077]).
Regarding claim 7, Stone, when modified by Kawamura, teaches the method of claim 1, wherein the component spectrum represents correlation between the measured Raman scattered elements and the stimulus (Kawamura: [0084]).
Regarding claim 8, Stone, when modified by Kawamura, teaches the method of claim 7, wherein the component spectrum represents a difference between the measured Raman scattered elements when the stimulus in a first state for example an “on” state, and the measured Raman scattered elements when the stimulus in a second state for example an “off” state (Kawamura: [0091] the extracted amplitude is mathematically equivalent to the difference between the signals in first state (theta is 0 degrees) and the second state (theta is 90 degrees)).
Regarding claim 9, Stone, when modified by Kawamura, teaches the method of claim 1, wherein detecting the one or more properties based on the detected variations in the measured Raman scattered elements comprises detecting the SERS probes (Stone: [0026], [0054]” the reporter molecules may be bound to nanoparticles to provide a surface enhanced Raman spectroscopy (SERS) effect for the detection of said one or more Raman spectral features arising from the reporter molecules”).
Regarding claim 10, Stone, when modified by Kawamura, teaches the method of claim 1, wherein the detecting the one or more properties comprises detecting one or more of:
particular states of the SERS probes;
binding states of the SERS probes to one or more target species;
a temperature at the SERS probes;
a pH at the SERS probes (stone: [0070]);
a density or quantity of the SERS probes; and
presence or absence of the SERS probes.
Regarding claim 11, Stone, when modified by Kawamura, the method of claim 1, teaches wherein each SERS probe comprises one or more metal nanoparticles, each metal nanoparticle carrying one or more Raman reporter molecules, wherein the elements of said probe light Raman scattered from the SERS probes are elements of the probe light scattered from the Raman reporter molecules (Stone: [0054], [0071]).
Regarding claim 12, Stone, when modified by Kawamura, teaches the method of claim 1, wherein the varying stimulus is one or more of: a non-optical or non-light stimulus; an ultrasound stimulus; a magnetic stimulus; a time varying ultrasound field stimulus; a time varying magnetic field stimulus a time varying light field stimulus (Kawamura: [0080] the polarization- modulated light constitutes a time varying light field stimulus); and a time varying microwave or terahertz wave field stimulus.
Regarding claim 14, Stone, when modified by Kawamura, teaches the method of claim 1, wherein a cycle time of the varying stimulus for inducing detected variations in the Raman scattered elements of the same or a corresponding cycle time, is between 0.001 and 100 seconds (Kawamura: [0091] example of the rotation frequency of the linear-polarized light 5 is 270 Hz. 270 Hz corresponds to a cycle time of approximately 0.0037 seconds which falls within the claimed range).
Regarding claim 15, Stone, when modified by Kawamura, teaches the method of claim 1, wherein the entry and collection regions are disposed on opposite sides of the sub-surface volume (Stone: [0066]).
Regarding claim 16, Stone, when modified by Kawamura, teaches the method of claim 1, comprising separately detecting the SERS probes for each of a plurality of different spatial offsets between the entry and collection regions; associating the detected SERS probes for each different spatial offset with a different depth or distribution of depth within the sample; detecting the one or more properties at each different depth or distribution of depth based on the detected variations in the measured Raman scattered elements (Stone: [0027], claim 27).
Regarding claim 17, Stone, when modified by Kawamura, teaches the method of claim 16, wherein the entry and collection regions are spatially offset by an offset in the range from 1 mm to 50 mm, and more preferably in the range from 3 mm to 20 mm (Stone: [0027]).
Regarding claim 18, Stone, when modified by Kawamura, teaches the method of claim 16, wherein the SERS probes are located at distances beneath the surface of the sample which are in the ranges of: at least 1 mm; from 1 mm to 80 mm; and from 3 mm to 50 mm (Stone: [0064]).
Regarding claim 19, Stone, when modified by Kawamura, teaches the method of claim 1, wherein the diffusely scattering sample has a diffuse scattering transport length of less than 4 mm (Stone [0063]).
Regarding claim 20, Stone, when modified by Kawamura, teaches the method of claim 1, wherein the stimulus is provided in the sub-surface volume such that a volume of the sample, within which the stimulus has a magnitude greater than 1/e of its corresponding peak spatial magnitude within that volume, or a volume of the sample in which the SERS probes can be detected, is limited to no more than 1000 mm3 or to no more than 100 mm3 (Kawamura: [0066]:the volume is about 3. 14 X (0.05 mm)2 X 0.1 mm= 0.000785 mm3 which is no more than 1000 mm3 or to no more than 100 mm3).
Regarding claim 21, Stone, when modified by Kawamura, teaches the method of claim 1, comprising repeating the method to detect the one or more properties at a plurality of different sub-surface volumes within the diffusely scattering sample, wherein for each such sub-surface volume the stimulus in varying form is provided to that sub-surface volume for the detection of the properties in that sub-surface volume (Stone: [0090], fig. 12, as the object rotates, detection is repeated for multiple of different sub-surface volumes within the diffusely scattering sample).
Regarding claim 22, Stone, when modified by Kawamura, teaches the method of claim 1, wherein the sample is an in-vivo portion of a human or animal body, and optionally wherein the surface of the sample is skin of the in-vivo portion (Stone: [0040]).
Regarding claim 23, claim 23 incorporates all the limitations of claim 1 with minor variations in the claimed language, in apparatus form, rather than method form. The reasons for the rejection of claim 1 apply to claim 23. Therefore, claim 23 is rejected under the same rationale.
Regarding claim 24, claim 24 incorporates all the limitations of claim 2 with minor variations in the claimed language, in apparatus form, rather than method form. The reasons for the rejection of claim 2 apply to claim 24. Therefore, claim 24 is rejected under the same rationale.
Regarding claim 25, claim 25 incorporates all the limitations of claim 3 with minor variations in the claimed language, in apparatus form, rather than method form. The reasons for the rejection of claim 3 apply to claim 25. Therefore, claim 25 is rejected under the same rationale.
Regarding claim 26, claim 26 incorporates all the limitations of claim 4 with minor variations in the claimed language, in apparatus form, rather than method form. The reasons for the rejection of claim 4 apply to claim 26. Therefore, claim 26 is rejected under the same rationale.
Regarding claim 27, claim 27 incorporates all the limitations of claim 12 with minor variations in the claimed language, in apparatus form, rather than method form. The reasons for the rejection of claim 12 apply to claim 27. Therefore, claim 27 is rejected under the same rationale.
Regarding claim 29, Stone, when modified by Kawamura, teaches the apperatus of claim 23, further comprising one or both of said SERS probes (Stone: [0026], [0054]” the reporter molecules may be bound to nanoparticles to provide a surface enhanced Raman spectroscopy (SERS) effect for the detection of said one or more Raman spectral features arising from the reporter molecules”) and said diffusely scattering sample ([0040]).
Regarding claim 30, claim 30 incorporates all the limitations of claim 1 with minor variations in the claimed language, in computer program product form, rather than method form. The reasons for the rejection of claim 1 apply to claim 30. Therefore, claim 30 is rejected under the same rationale.
Regarding claim 31, claim 31 incorporates all the limitations of claim 3 with minor variations in the claimed language, in computer program product form, rather than method form. The reasons for the rejections of claim 3 apply to claim 31. Therefore, claim 31 is rejected under the same rationale.
Regarding claim 32, Claim 32 incorporates all the limitations of claim 4 with minor variations in the claimed language, in computer program product form, rather than method form. The reasons for the rejection of claim 4 apply to claim 32. Therefore, claim 32 is rejected under the same rationale.
Claims 13 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Stone (US 20190277766 A1) in view of Kawamura (US 20120029326 A1), and further in view of Jarvik (US20120108918A1).
Regarding claim 13, Stone, when modified by Kawamura, teaches the method of claim 1, but fails to disclose wherein the varying stimulus is a time varying ultrasound field generated by a high-intensity focussed ultrasound transducer having a central aperture, and one or both of the entry region and collection region are located within or visible through the central aperture.
However, Jarvik teaches wherein the varying stimulus is a time varying ultrasound field generated by a high-intensity focussed ultrasound transducer ([0087], [0091]), having a central aperture (the hollow interior of the plastic cone) ([0138]), and one or both of the entry region and collection region are located within or visible through the central aperture ([0138] Two lasers which provide optical delivery/collection are positioned such as their beam pass through the central region of the transducer assembly and converge at the ultrasound focal point. So the optical path (entry region for delivery) is located within and visible through the central aperture of the ultrasound transducer).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Stone and Kawamura by incorporating wherein the varying stimulus is a time varying ultrasound field generated by a high-intensity focussed ultrasound transducer having a central aperture, and one or both of the entry region and collection region are located within or visible through the central aperture providing predictable results of improved targeting accuracy.
Regarding claim 28, claim 28 incorporates all the limitations of claim 13 with minor variations in the claimed language, in apparatus form, rather than method form. The reasons for the rejection of claim 13 apply to claim 28. Therefore, claim 28 is rejected under the same rationale.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Kuo (US 20110188035 A1)
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/MOHAMED DOUMBIA/ Examiner, Art Unit 2877 /MICHELLE M IACOLETTI/Supervisory Patent Examiner, Art Unit 2877