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 .
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.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites the limitation "the image" in claim 1. There is insufficient antecedent basis for this limitation in the claim. Although an image is defined in claim 7, claim 8 does not depend upon claim 7.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 3, 10, 11, and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. U.S. PGPUB No. 2010/0301199.
Regarding claim 1, Chen discloses a system for sampling material to a detecting means, the system comprising a housing for a sample 3 and a fluid immersing the sample (Chen illustrates a housing in figure 1 including sample 3, which is described as immersed in a fluid: “The at least one analyte or analyte precursor can be provided in a dissolved, colloidal, suspended, or liquid state” [0023]), a transducer 2 configured to emit focused ultrasound waves towards a target on interface between the sample and the fluid for removing material from the sample to the fluid (“a piezoelectric transducer 2 connected to a sinusoidal drive 1 that can subject analyte 3 in a sample to ultrasound” [0013]) and for producing an acoustic stream in the fluid (“the ultrasound causes formation of an amount of ionized analyte detectable by mass spectrometry” [0018]), and a feeding means (illustrated in figure 1: “a series of capillaries that draw ionized analyte from the sample, including a heating capillary 4” [0013]) configured to be positioned between the transducer and the interface (figure 1 illustrates that at least one of the series of capillaries is positioned between the transducer 2 and the interface between the liquid and at least some of the sample 3), and a second end configured to be connected to the detecting means 6 (as illustrated in figure 1), and fluid transport means between the first end and the second end, the feeding means configured to transport at least part of the removed material to the detecting means (“These small droplets were drawn by capillary action through the first capillary and introduced to the heating capillary… Analyte within the droplets was desolvated as it passed through the heating capillary. The desolvated analyte then entered the ion trap mass analyzer” [0065]).
Regarding claim 3, Chen discloses that the frequency of the ultrasound is at least 20 kHz (“The methods of the invention relate to subjecting the sample to ultrasound with a power, frequency, and duration effective to ionize the analyte or the analyte precursor… In some embodiments, the frequency of the ultrasound can range from 10 kHz to 100 MHz, for example, 100 kHz to 10 MHz, 1 MHz to 3 MHz, or about 1.7 MHz” [0034]).
Regarding claim 10, Chen discloses a means for collecting at least part of the removed material (“a series of capillaries that draw ionized analyte from the sample, including a heating capillary 4” [0013]).
Regarding claim 11, Chen discloses a detecting means comprising a system according to claim 1 (as described in detail, above, with respect to the rejection of claim 1).
Regarding claim 12, Chen discloses a detecting means selected from one or more of: a mass spectrometer, Raman spectrometer, NMR spectrometer, IR spectrometer, UV spectrophotometer, scanning electron microscope, atomic force microscope, quartz crystal balance, dynamic light scattering meter, high pressure liquid chromatograph, x- ray diffractometer, activity assay means, immunoassay means, and Raman spectrometer (“Methods and systems for ultrasound ionization mass spectrometry are provided” [Abstract]).
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.
Claim(s) 2, 14, 15, 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. U.S. PGPUB No. 2010/0301199.
Regarding claim 2, Chen discloses the claimed invention except that while Chen discloses that “The methods of the invention relate to subjecting the sample to ultrasound with a power, frequency, and duration effective to ionize the analyte or the analyte precursor. In some embodiments, the power of the ultrasound is at least 0.1 W, and can range from 0.1 W to 1000 W, for example, 1 W to 1000 W, 2 W to 1000 W, 1 W to 100 W, 2 W to 10 W, 2 W to 6 W, or about 4 W [0034], there is no explicit disclosure that the intensity of the ultrasound at the target is at least 1 W/cm2. It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to select an intensity of the ultrasound at the target of at least 1 W/cm2 since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. One would have been motivated to select an intensity of the ultrasound at the target of at least 1 W/cm2 for the purpose of ensuring a desired amount of ionization based on the type of sample to be analyzed so as to generate enough sample ions for analysis. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235.
Regarding claim 14, Chen discloses a method of feeding material from a sample to a detecting means, the method comprising immersing the sample into a fluid (Chen illustrates a housing in figure 1 including sample 3, which is described as immersed in a fluid: “The at least one analyte or analyte precursor can be provided in a dissolved, colloidal, suspended, or liquid state” [0023]), selecting a target on an interface between the sample and the fluid, subjecting the target to focused ultrasound waves (“a piezoelectric transducer 2 connected to a sinusoidal drive 1 that can subject analyte 3 in a sample to ultrasound” [0013] – “the ultrasound causes formation of an amount of ionized analyte detectable by mass spectrometry” [0018]), thereby removing material from the sample and producing an acoustic stream in the fluid comprising removed material (“the ultrasound causes formation of an amount of ionized analyte detectable by mass spectrometry” [0018]), and feeding at least part of the fluid comprising the removed material to the detecting means (“These small droplets were drawn by capillary action through the first capillary and introduced to the heating capillary… Analyte within the droplets was desolvated as it passed through the heating capillary. The desolvated analyte then entered the ion trap mass analyzer” [0065]). Chen discloses the claimed invention except that while Chen discloses that “The methods of the invention relate to subjecting the sample to ultrasound with a power, frequency, and duration effective to ionize the analyte or the analyte precursor. In some embodiments, the power of the ultrasound is at least 0.1 W, and can range from 0.1 W to 1000 W, for example, 1 W to 1000 W, 2 W to 1000 W, 1 W to 100 W, 2 W to 10 W, 2 W to 6 W, or about 4 W [0034], there is no explicit disclosure that the intensity of the ultrasound at the target is at least 1 W/cm2. It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to select an intensity of the ultrasound at the target of at least 1 W/cm2 since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. One would have been motivated to select an intensity of the ultrasound at the target of at least 1 W/cm2 for the purpose of ensuring a desired amount of ionization based on the type of sample to be analyzed so as to generate enough sample ions for analysis. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235.
Regarding claim 15, Chen discloses that at least part of the fluid comprising the removed material is fed to the collecting means (“These small droplets were drawn by capillary action through the first capillary and introduced to the heating capillary… Analyte within the droplets was desolvated as it passed through the heating capillary. The desolvated analyte then entered the ion trap mass analyzer” [0065]).
Regarding claim 16, Chen discloses that the frequency of the ultrasound is at least 20 kHz (“The methods of the invention relate to subjecting the sample to ultrasound with a power, frequency, and duration effective to ionize the analyte or the analyte precursor… In some embodiments, the frequency of the ultrasound can range from 10 kHz to 100 MHz, for example, 100 kHz to 10 MHz, 1 MHz to 3 MHz, or about 1.7 MHz” [0034]).
Claim(s) 4, 6, 9, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. U.S. PGPUB No. 2010/0301199 in view of Van Berkel et al. U.S. PGPUB No. 2013/0294971.
Regarding claim 4, Chen discloses the claimed invention except that while Chen discloses that “a series of capillaries that draw ionized analyte from the sample, including a heating capillary 4” [0013], there is no explicit disclosure of a means for adjusting distance h between the interface and the first end.
Van Berkel discloses a system for sampling material to a detecting means, the system comprising a housing 14 for a sample S and a fluid 19 immersing the sample (“a liquid junction 62 between the surface 54 of the specimen (S) and the solvent 19 in fluidic communication with the probe 12” [0031]), and a feeding means 16, having a first end connected to the interface 62 between the sample S and the fluid 19 and a second end configured to be connected to the detecting means (as illustrated in figure 1), and fluid transport means 20 between the first end and the second end (“The sampling capillary 20 can be in fluid communication with the analytical instrument 32 via a sampling outlet 50” [0035]), the feeding means 16 configured to transport at least part of the removed material to the detecting means (as illustrated in figure 1); and means 28 for adjusting distance h between the interface and the first end of feeding means 16 (“The adjuster 28 can be adapted for moving the outer capillary tube tip 24 and the inner capillary tube tip 26 longitudinally relative to one another. The adjuster 28 can be any device capable of moving the outer capillary tube 14 relative to the inner capillary tube 16. Exemplary adjusters 28 can be motors including, but are not limited to, electric motors (e.g., AC motors, DC motors, electrostatic motors, servo motors, etc.), hydraulic motors, pneumatic motors, translational stages, and combinations thereof” [0025]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Chen with the means for adjusting, as described in Van Berkel, in order to ensure an optimal flow path of removed sample material for downstream analysis, so as to prevent the unnecessary loss of sample material between ablation and transportation through the feeding means.
Regarding claim 6, Chen discloses the claimed invention except that while Chen discloses that “a series of capillaries that draw ionized analyte from the sample, including a heating capillary 4” [0013], there is no explicit disclosure of a means configured to move the transducer and/or means configured to move the housing.
Van Berkel discloses a system for sampling material to a detecting means, the system comprising a housing 14 for a sample S and a fluid 19 immersing the sample (“a liquid junction 62 between the surface 54 of the specimen (S) and the solvent 19 in fluidic communication with the probe 12” [0031]), and a feeding means 16, having a first end connected to the interface 62 between the sample S and the fluid 19 and a second end configured to be connected to the detecting means (as illustrated in figure 1), and fluid transport means 20 between the first end and the second end (“The sampling capillary 20 can be in fluid communication with the analytical instrument 32 via a sampling outlet 50” [0035]), the feeding means 16 configured to transport at least part of the removed material to the detecting means (as illustrated in figure 1); and means 28 configured to move the housing 14 (“The adjuster 28 can be adapted for moving the outer capillary tube tip 24 and the inner capillary tube tip 26 longitudinally relative to one another. The adjuster 28 can be any device capable of moving the outer capillary tube 14 relative to the inner capillary tube 16. Exemplary adjusters 28 can be motors including, but are not limited to, electric motors (e.g., AC motors, DC motors, electrostatic motors, servo motors, etc.), hydraulic motors, pneumatic motors, translational stages, and combinations thereof” [0025]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Chen with the means for adjusting, as described in Van Berkel, in order to ensure an optimal flow path of removed sample material for downstream analysis, so as to prevent the unnecessary loss of sample material between ablation and transportation through the feeding means.
Regarding claim 9, Chen discloses the claimed invention except that while Chen discloses that “a series of capillaries that draw ionized analyte from the sample, including a heating capillary 4” [0013], there is no explicit disclosure of a means configured to control one or more of: pH of the fluid, temperature of the fluid, velocity of the fluid, water content of a non-aqueous fluid, relative humidity of a gaseous fluid.
Van Berkel discloses a system for sampling material to a detecting means, the system comprising a housing 14 for a sample S and a fluid 19 immersing the sample (“a liquid junction 62 between the surface 54 of the specimen (S) and the solvent 19 in fluidic communication with the probe 12” [0031]), and a feeding means 16, having a first end connected to the interface 62 between the sample S and the fluid 19 and a second end configured to be connected to the detecting means (as illustrated in figure 1), and fluid transport means 20 between the first end and the second end (“The sampling capillary 20 can be in fluid communication with the analytical instrument 32 via a sampling outlet 50” [0035]), the feeding means 16 configured to transport at least part of the removed material to the detecting means (as illustrated in figure 1); and means configured to control velocity of the fluid (“increasing the sampling capillary flow rate relative to the solvent capillary flow rate” [0005] – “the pumps 46 and 64 can be syringe pumps, positive displacement pumps, nebulization or electrospraying devices, or chambers with sufficient pressure differentials to induce fluid flow” [0036]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Chen with the means for adjusting, as described in Van Berkel, in order to ensure an optimal flow rate of removed sample material for downstream analysis, so as to control an amount or rate of analyte to be optimized for the particular downstream analyzer.
Regarding claim 17, Chen discloses the claimed invention except that while Chen discloses that “a series of capillaries that draw ionized analyte from the sample, including a heating capillary 4” [0013], there is no explicit disclosure of a means for adjusting distance h between the interface and the first end.
Van Berkel discloses a system for sampling material to a detecting means, the system comprising a housing 14 for a sample S and a fluid 19 immersing the sample (“a liquid junction 62 between the surface 54 of the specimen (S) and the solvent 19 in fluidic communication with the probe 12” [0031]), and a feeding means 16, having a first end connected to the interface 62 between the sample S and the fluid 19 and a second end configured to be connected to the detecting means (as illustrated in figure 1), and fluid transport means 20 between the first end and the second end (“The sampling capillary 20 can be in fluid communication with the analytical instrument 32 via a sampling outlet 50” [0035]), the feeding means 16 configured to transport at least part of the removed material to the detecting means (as illustrated in figure 1); and means 28 for adjusting distance h between the interface and the first end of feeding means 16 (“The adjuster 28 can be adapted for moving the outer capillary tube tip 24 and the inner capillary tube tip 26 longitudinally relative to one another. The adjuster 28 can be any device capable of moving the outer capillary tube 14 relative to the inner capillary tube 16. Exemplary adjusters 28 can be motors including, but are not limited to, electric motors (e.g., AC motors, DC motors, electrostatic motors, servo motors, etc.), hydraulic motors, pneumatic motors, translational stages, and combinations thereof” [0025]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Chen with the means for adjusting, as described in Van Berkel, in order to ensure an optimal flow path of removed sample material for downstream analysis, so as to prevent the unnecessary loss of sample material between ablation and transportation through the feeding means. Chen and Van Berkel disclose the claimed invention except that there is no explicit disclosure that the distance h is at least 1 mm. It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to select the distance h to be 1 mm since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. One would have been motivated to select the distance h to be 1 mm for the purpose of ensuring an optimal flow path of removed sample material for downstream analysis, so as to prevent the unnecessary loss of sample material between ablation and transportation through the feeding means. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. U.S. PGPUB No. 2010/0301199 in view of Otsuka U.S. PGPUB No. 2014/0070094.
Regarding claim 8; Chen discloses the claimed invention except that while Chen discloses mass spectrometric detection of a sample (“Analytes in a sample are ionized by subjecting them to ultrasound, facilitating their analysis by mass spectrometry” [Abstract]), there is no explicit disclosure of an imaging means for producing an image of the sample.
Otsuka discloses “an imaging mass spectrometry (IMS) has been developed, which displays an image indicating what kind of substance exists on which part of the surface” [0005].
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Chen with the imaging means of Otsuka in order to provide a visualization of a sample composition in analyzing the composition.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. U.S. PGPUB No. 2010/0301199 in view of Ellson et al. U.S. PGPUB No. 2002/0109084.
Regarding claim 13, Chen discloses the claimed invention except that while Chen discloses “Methods and systems for ultrasound ionization mass spectrometry” [Abstract], and that “Mass spectrometry generally involves obtaining analyte in an ionized state. Techniques used to achieve this step include… Electrospray (ES)” [0002], there is no explicit disclosure that the detecting means is an electrospray ionization mass spectrometer.
Ellson discloses an ultrasonic nebulization method (“droplets may be produced through a number of methods such as those that employ ultrasonic energy” [0003]) coupled with electrospray ionization mass spectrometry for analyzing the sample (“Capillaries with extremely small bore integral to other devices such as openings for loading microchannels of microfluidic devices can be as small as 1 µm… In the context of delivery to a mass analyzer in electrospray type mass spectrometry, the inner diameter of capillaries may range from about 0.1 to about 3 mm” [0039]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Chen with the electrospray ionization of Ellson in order to select an energy of the ultrasonic nebulization which gently removes solid samples for analysis and which only later ionizes the sample, thereby providing a soft ionization technique which preserved more sample ions for analysis and thereby selecting an ionization energy which delivers ions having optimal qualities for analysis.
Allowable Subject Matter
Claim 5 and 18 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 5; Chen et al. U.S. PGPUB No. 2010/0301199 discloses “subjecting an analyte or analyte precursor to ultrasound, wherein the ultrasound causes formation of an amount of ionized analyte detectable by mass spectrometry” [0018] but does not disclose a means for moving the focal point of the ultrasound waves.
Datwani et al. U.S. PGPUB No. 2019/0157061 discloses an analysis system “to generate acoustic radiation toward the reservoir and into the fluid sample in a manner effective to eject a droplet of the fluid sample from the fluid surface into a sampling tip of a continuous flow sampling probe” [0017], wherein “A vibrational element or ultrasonic transducer is used to generate acoustic radiation. An ultrasonic transducer typically includes an actuator and a focusing element that concentrates acoustic energy produced by the actuator” [0099]. However, Datwani does not disclose that the focal point can be moved, and therefore does not disclose a means for moving the focal point of the ultrasound waves.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for sampling material to a detecting means, the system comprising: a housing for a sample and a fluid for immersing the sample; a transducer configured to emit focused ultrasound waves towards a target on interface between the sample and the fluid for removing material from the sample to the fluid and for producing an acoustic stream in the fluid; and means for moving a focal point of the ultrasound waves.
Regarding claim 18; Chen et al. U.S. PGPUB No. 2010/0301199 discloses the claimed invention except that while Chen discloses mass spectrometric detection of a sample (“Analytes in a sample are ionized by subjecting them to ultrasound, facilitating their analysis by mass spectrometry” [Abstract]), there is no explicit disclosure of an imaging means for producing an image of the sample.
Otsuka U.S. PGPUB No. 2014/0070094 discloses “an imaging mass spectrometry (IMS) has been developed, which displays an image indicating what kind of substance exists on which part of the surface” [0005]. However, Otsuka does not disclose selecting a target on an interface between a sample and a fluid based on imaging.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for sampling material to a detecting means, the system comprising: a housing for a sample and a fluid for immersing the sample; an imaging means configured to select a target on an interface between the sample and the fluid based on an image of the sample; and a transducer configured to emit focused ultrasound waves towards the target for removing material from the sample to the fluid and for producing an acoustic stream in the fluid.
Claim 7 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Regarding claim 7; Chen et al. U.S. PGPUB No. 2010/0301199 discloses the claimed invention except that while Chen discloses mass spectrometric detection of a sample (“Analytes in a sample are ionized by subjecting them to ultrasound, facilitating their analysis by mass spectrometry” [Abstract]), there is no explicit disclosure of an imaging means for producing an image of the sample.
Otsuka U.S. PGPUB No. 2014/0070094 discloses “an imaging mass spectrometry (IMS) has been developed, which displays an image indicating what kind of substance exists on which part of the surface” [0005]. However, Otsuka does not disclose selecting a target on an interface between a sample and a fluid based on imaging.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for sampling material to a detecting means, the system comprising: a housing for a sample and a fluid for immersing the sample; an imaging means configured to select a target on an interface between the sample and the fluid based on an image of the sample; and a transducer configured to emit focused ultrasound waves towards the target for removing material from the sample to the fluid and for producing an acoustic stream in the fluid.
Conclusion
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/JASON L MCCORMACK/Examiner, Art Unit 2881