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 .
Summary
This action is responsive to the Request for Continued Examination filed on 02/23/2026. Applicant has submitted Claims 1, 4-13, and 15-22 for examination.
Examiner finds the following: 1) Claims 1, 4-13, and 15-20 are rejected; 2) no claims objected to; and 3) no claims allowable.
Request for Continued Examination
Receipt is acknowledged of a Request for Continued Examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e) and a submission, filed on 02/23/2026.
Response to Arguments and Remarks
Examiner respectfully acknowledges Applicant's arguments, remarks, and amendments filed January 20th, 2026.
Applicant did not submit new arguments with the RCE, as such, Examiner responds to the arguments and most recent claim set, both of which were filed 01/20/2026. Examiner responded to these arguments in the Advisory Action filed 01/28/2026, which is reproduced below.
Regarding Applicant's Section II Argument, Examiner agrees that Fang does not explicitly disclose 100 or more particles. This is why Examiner relied on the Duplication of Parts argument. Examiner is not persuaded this is novel over the prior art.
Regarding Applicant's Section III Argument, Examiner grants that the number of sensors and processing to scale Fang up to the claimed invention would take a lot of time and precision, but maintains that PHOSITA would have the skills to do so. As such, Examiner is not persuaded.
Additionally, as part of Applicant's Section III Argument, Applicant indicated particular aspects and systems, such as systems to account for signal noise, plasmonic coupling, etc., that Fang would lack. Examiner recommends amending such into the claims to better differentiate against Fang, but any such amendments would require further searching and consideration.
Regarding Applicant's Section IV Argument, Examiner maintains the Duplication of Parts. As Examiner previously noted, citing to Fang [0083], for Fang to determine inter-particle distance information, Fang would inherently be tracking information related to two or more particles. Examiner grants that "two or more" is not "100 or more," but relied on a Duplication of Parts argument to indicate that the technology for multiple particle tracking is known in the art. PHOSITA would have been able to scale up Fang for greater particle counts using the same principles and technology disclosed by Fang. As noted above, Examiner grants that the number of sensors and processing to scale Fang up to the claimed invention would take a lot of time and precision, but maintains that PHOSITA would have the skills to do so. As such, Examiner is not persuaded.
Regarding Applicant's Section V Argument, again, Examiner notes that Fang would inherently be tracking information related to two or more particles. As such, Examiner is not persuaded.
Regarding Applicant's Section VI Argument, again, Examiner notes that Fang would inherently be tracking information related to two or more particles. If Applicant is able to definitively show that Fang is determining inter-particle distances without tracking two or more particles, Examiner would agree that Fang would not read on the claims as currently applied. However, as is, Examiner is not persuaded.
Examiner suggests that Applicant focuses on the structure of how the claimed invention is different from the cited references, most specifically Fang, and what structures Fang lacks in comparison. Claiming such structures, especially ones that would interfere with Fang's operation or assist in tracking 100 or more particles in a manner that is not disclosed by Fang would be a stronger response, in Examiner's opinion. Based on Examiner's review of the prior art references and claimed invention, Examiner does not have a specific recommendation at this time but will reach out to Applicant if Examiner does come up with recommendation.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or non-obviousness.
Claims 1, 4-13, and 15-22 are rejected under 35 U.S.C. 103 as being unpatentable over Fang (US 20210318245 A1).
Regarding Claim 1, Fang discloses:
A method of tracking molecular dynamics, the method comprising:
introducing an incident light (Fang, FIG. 2B, [0092], incident light 156) toward a second surface (Fang, FIG. 2B, [0092], showing incident light 156 entering substrate 122 on the side of 122a) of a substrate (Fang, FIG. 2B, [0092], substrate 122) to induce a plasmonic wave (Fang, FIG. 2B, [0092], “The plasmon then creates an evanescent wave field that extends into the medium on either side of the gold film 122b”) at least proximal to a first surface of the substrate (Fang, FIG. 2B, [0092], gold film 122b), which first surface comprises a population of particles connected to the first surface via one or more first biomolecules (Fang, [0076], “single particle orientation and rotational tracking (SPORT) of plasmonic nanoparticles in various chemical and biological systems,” and [0097], “The stability of a microscopy imaging system is very critical for precisely recovering biological, chemical events especially when it requires to record the data for long period”); and,
detecting a change in position … of the particles in the population along at least three dimensions … to generate statistics in a single measurement, which three dimensions comprise two substantially lateral dimensions and an axial dimension (Fang, [0098], “FIG. 5B shows a design of a multi-modality, multi-color, 4-channel imaging module that can enable the 3D single particle tracking capability through bifocal imaging or point spread function (PSF) engineering such as parallax imaging, double-helix PSF, astigmatism, etc.”), from a change in intensity of the incident light reflected at an interface of the first surface of the substrate using a surface plasmon resonance microscopy (SPRM) device (Fang, [0076], “DIC microscopy to transform it into a primary research tool for single particle orientation and rotational tracking (SPORT) of plasmonic nanoparticles in various chemical and biological systems,” and FIG. 2A, [0090], “The incident light 156 is converted to surface plasmon resonance (SPR) at the electronically conducting gold film 122b. The plasmon then creates an evanescent wave field that extends into the medium on either side of the gold film 122b”), thereby tracking the molecular dynamics (Fang, [0090], “The ratio of fluorescence intensities from sequential acquisitions with fixed-angle TIRFM and wide-field microscopy [65-66] or from two-angle TIRFM [67-70] can give good estimates of axial distances, while more depth-resolved information is obtainable with prism or objective-based variable-angle TIRFM [62, 7-74] where a stack of multi-angle images contains the integrated fluorescence intensity over various thicknesses of the sample”).
Fang discloses the above but does not explicitly disclose:
… detecting a change in position of 100 or more of the particles…
However, Fang discloses particle detection in [0098] and Examiner previously cited [0083]:
The coupling of the Raman and DIC spectroscopy allows us to correlate the surface enhancement and inter-particle distance information.” (Examiner notes for Fang to determine inter-particle distance information, Fang would inherently be tracking information related to two or more particles.)
Pursuant to MPEP 2144.04(VI)(B) – Duplication of Parts:
[T]he court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced.
Fang discloses disclosure of multiple particles, but does not explicitly disclose “100 or more” particles. PHOSITA would be aware of how to add additional means for detection of additional particles. Based on Examiner’s review of the specification and prior art, the additional means for detection of additional particles would not introduce any new or unexpected results. Therefore, it would have been obvious to PHOSITA before Applicant’s filing date to include additional means of detection of additional particles and would require routine skill in the art.
Regarding Claim 4, Fang discloses Claim 1, and Fang further discloses:
… further comprising detecting the change in position of the particles in the population along a rotational dimension (Fang, [0076], “single particle orientation and rotational tracking (SPORT)”).
Regarding Claim 5, Fang discloses Claim 1, and Fang further discloses:
… comprising detecting changes in position of the particles in the population with a precision of 10 nanometers or less (Fang, [0090], “auto-calibrated scanning-angle prism-type total internal reflection fluorescence microscopy for nanometer-precision axial position determination and optional variable-illumination-depth pseudo total internal reflection microscopy”).
Regarding Claim 6, Fang discloses Claim 1, and Fang further discloses:
… comprising detecting changes in position of the particles in the population with a precision of less than one nanometer in the axial dimension (Fang, FIG. 1C, [0100], “Raman spectra can be taken from sub-micrometer areas of samples. Therefore, a very high-resolution correlation between RDIC images and Raman spectra can be obtained”).
Regarding Claim 7, Fang discloses Claim 1, but does not explicitly disclose:
… comprising detecting changes in position of the particles in the population at least in the axial dimension at a frame rate of about one kilohertz (kHz) or less.
However, the frame rate of the microscope is a result-effective variable. In that, if the frame rate was too slow, it would not be able to properly track the particles, and if the frame rate were too high, it could overload the system.
Therefore, it would have been obvious to one having ordinary skill in the art before applicant’s filing date to include the use of various frame rates as the frame rate is based on a result effective variable and would require routine skill in the art. Furthermore, it has been held that that determining the optimum value of a result effective variable involves only routine skill in the art (see MPEP 2144.05 (II (A) and (B)).
Regarding Claim 8, Fang discloses Claim 1, and Fang further discloses:
… wherein the duration comprises a time resolution of 100 milliseconds or less (Fang, [0084], “Raman spectra can be taken on the picosecond time scale, providing information on short-lived species such as excited states and reaction intermediates”).
Regarding Claim 9, Fang discloses Claim 1, and Fang further discloses:
… further comprising one or more second biomolecules connected to at least some of the particles in the population, wherein the method comprises tracking interactions of the second biomolecules with one or more other biomolecules (Fang, [0005], “Optical microscopy imaging has been playing an increasingly important role in the investigations of nanomaterials and biomaterials and fundamental chemical processes (e.g., diffusion, adsorption and reaction) at the molecular and nanoscale level”).
Regarding Claim 10, Fang discloses Claim 1, and Fang further discloses:
… comprising tracking the molecular dynamics in substantially real-time (Fang, [0077], “The advantages of the RDIC microscopy over other conventional methods such as electron microscopy and scanning probe microscopy include noninvasive and nondestructive rapid characterization, relatively simple sample preparation, dynamic measurements in real time, and is relatively less expensive”).
Regarding Claim 11, Fang discloses Claim 1, and Fang further discloses:
… wherein the first biomolecules are label-free (Fang, [0088], “to provide an accurate, high throughput, non-destructive, label-free and in-situ available analytical method”).
Regarding Claim 12, Fang discloses Claim 1, and Fang further discloses:
… comprising determining an axial position of a given z particle using the formula
I
=
I
0
e
-
z
d
, where I is the mean image intensity, I0 is the intensity when the given particle is in contact with the first surface and d is the decay constant of an evanescent field that comprises the given particle (Examiner notes that this claim is directed towards a known formula related to the Goos–Hänchen Effect / Shift, and is known in the art).
Regarding Claim 13, Fang discloses:
A system for tracking molecular dynamics, comprising:
a surface plasmon resonance microscopy (SPRM) device (Fang, [0076], “DIC microscopy to transform it into a primary research tool for single particle orientation and rotational tracking (SPORT) of plasmonic nanoparticles in various chemical and biological systems,” and FIG. 2A, [0090], “The incident light 156 is converted to surface plasmon resonance (SPR) at the electronically conducting gold film 122b. The plasmon then creates an evanescent wave field that extends into the medium on either side of the gold film 122b”) that comprises:
a substrate (Fang, FIG. 2B, [0092], substrate 122) having a first surface and a second surface opposite the first surface (Fang, FIG. 2B, [0092], substrate 122 having sides 122a and 122b), wherein the first surface comprises a population of particles connected to the first surface (Fang, FIG. 2B, [0092], gold film 122b) via one or more first biomolecules (Fang, [0076], “single particle orientation and rotational tracking (SPORT) of plasmonic nanoparticles in various chemical and biological systems,” and [0097], “The stability of a microscopy imaging system is very critical for precisely recovering biological, chemical events especially when it requires to record the data for long period”);
an objective lens or a prism disposed proximal to the second surface of the substrate (Fang, FIG. 2B, [0092], prism 157);
a light source configured to introduce light through the objective lens or the prism (Fang, FIG. 2B, [0092], incident light 156) to induce a plasmonic wave at least proximal to the first surface of the substrate (Fang, FIG. 2B, [0092], “The plasmon then creates an evanescent wave field that extends into the medium on either side of the gold film 122b”);
a detector configured to collect light reflected from the substrate (Fang, FIG. 1, [0087], detector 149); and …
…introducing an incident light (Fang, FIG. 2B, [0092], incident light 156) toward a second surface (Fang, FIG. 2B, [0092], showing incident light 156 entering substrate 122 on the side of 122a) of a substrate (Fang, FIG. 2B, [0092], substrate 122) from a light source (Fang, FIG. 1, laser 151) to induce a plasmonic wave (Fang, FIG. 2B, [0092], “The plasmon then creates an evanescent wave field that extends into the medium on either side of the gold film 122b”) at least proximal to a first surface of the substrate (Fang, FIG. 2B, [0092], gold film 122b), which first surface comprises a population of particles connected to the first surface (Fang, [0076], “single particle orientation and rotational tracking (SPORT) of plasmonic nanoparticles in various chemical and biological systems,” and [0097], “The stability of a microscopy imaging system is very critical for precisely recovering biological, chemical events especially when it requires to record the data for long period”);
detecting a change in position … of the particles in the population along at least three dimensions substantially simultaneously to generate statistics in a single measurement (Fang, [0098], “FIG. 5B shows a design of a multi-modality, multi-color, 4-channel imaging module that can enable the 3D single particle tracking capability through bifocal imaging or point spread function (PSF) engineering such as parallax imaging, double-helix PSF, astigmatism, etc.”), which three dimensions comprise two substantially lateral dimensions and an axial dimension, from a change in intensity of the incident light reflected at an interface of the first surface of the substrate using the SPRM device (Fang, [0090], “The ratio of fluorescence intensities from sequential acquisitions with fixed-angle TIRFM and wide-field microscopy [65-66] or from two-angle TIRFM [67-70] can give good estimates of axial distances, while more depth-resolved information is obtainable with prism or objective-based variable-angle TIRFM [62, 7-74] where a stack of multi-angle images contains the integrated fluorescence intensity over various thicknesses of the sample”).
Fang discloses the above but does not explicitly disclose:
… detecting a change in position of 100 or more of the particles…
However, Fang discloses particle detection in [0098] and Examiner previously cited [0083]:
The coupling of the Raman and DIC spectroscopy allows us to correlate the surface enhancement and inter-particle distance information.” (Examiner notes for Fang to determine inter-particle distance information, Fang would inherently be tracking information related to two or more particles.)
Pursuant to MPEP 2144.04(VI)(B) – Duplication of Parts:
[T]he court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced.
Fang discloses disclosure of multiple particles, but does not explicitly disclose “100 or more” particles. PHOSITA would be aware of how to add additional means for detection of additional particles. Based on Examiner’s review of the specification and prior art, the additional means for detection of additional particles would not introduce any new or unexpected results. Therefore, it would have been obvious to PHOSITA before Applicant’s filing date to include additional means of detection of additional particles and would require routine skill in the art.
Fang discloses the above but does not explicitly disclose:
… a controller that comprises, or is capable of accessing, computer readable media comprising non-transitory computer-executable instructions which, when executed by at least one electronic processor, perform at least:
However, Examiner understands Fang to be using a computer / processor / controller to manage Fang’s apparatus. For example, from Fang, with emphasis added:
Fang, [0076], “single particle orientation and rotational tracking (SPORT) of plasmonic nanoparticles in various chemical and biological systems,”
Fang, [0084], “Raman spectra can be taken on the picosecond time scale, providing information on short-lived species such as excited states and reaction intermediates.”
Fang, [0090], “auto-calibrated scanning-angle prism-type total internal reflection fluorescence microscopy for nanometer-precision axial position determination and optional variable-illumination-depth pseudo total internal reflection microscopy.”
Fang, [0098], “FIG. 5B shows a design of a multi-modality, multi-color, 4-channel imaging module that can enable the 3D single particle tracking capability through bifocal imaging or point spread function (PSF) engineering such as parallax imaging, double-helix PSF, astigmatism, etc.”
Examiner understands Fang to be using a computer / processor / controller to manage all of the above cited aspects of Fang’s apparatus. Examiner is unsure how Fang would operate as disclosed without a computer / processor / controller.
It would have been obvious to PHOSITA before the effective filing date of the claimed invention that Fang was using a computer / processor / controller to manage Fang’s apparatus. PHOSITA would have known about the uses of computers / processors / controllers in the art and how to use them to modify Fang. PHOSITA would have been motivated to do this as a combination of prior art elements according to known methods to yield predictable results (See MPEP § 2143 (I)(A)), specifically the use of computers / processors / controllers to manage a spectroscopy apparatus.
Regarding Claim 15, Fang discloses Claim 13, and Fang further discloses:
… wherein the non-transitory computer-executable instructions which, when executed by the electronic processor, further perform at least: detecting the change in position of the particles in the population along a rotational dimension (Fang, [0076], “single particle orientation and rotational tracking (SPORT)”).
Regarding Claim 16, Fang discloses Claim 13, and Fang further discloses:
… wherein the duration comprises a time resolution of 100 milliseconds or less (Fang, [0084], “Raman spectra can be taken on the picosecond time scale, providing information on short-lived species such as excited states and reaction intermediates”).
Regarding Claim 17, Fang discloses Claim 13, and Fang further discloses:
… further comprising one or more second biomolecules connected to at least some of the particles in the population (Fang, [0005], “Optical microscopy imaging has been playing an increasingly important role in the investigations of nanomaterials and biomaterials and fundamental chemical processes (e.g., diffusion, adsorption and reaction) at the molecular and nanoscale level”).
Regarding Claim 18, Fang discloses Claim 13, and Fang further discloses:
… wherein the first biomolecules are label-free (Fang, [0088], “to provide an accurate, high throughput, non-destructive, label-free and in-situ available analytical method”).
Regarding Claim 19, Fang discloses Claim 13, and Fang further discloses:
… wherein the substrate comprises an Au coating (Fang, FIG. 2B, [0092], gold film 122b).
Regarding Claim 20, Fang discloses:
A computer readable media comprising non-transitory computer executable instruction which, when executed by at least electronic processor, perform at least:
introducing an incident light (Fang, FIG. 2B, [0092], incident light 156) toward a second surface (Fang, FIG. 2B, [0092], showing incident light 156 entering substrate 122 on the side of 122a) of a substrate (Fang, FIG. 2B, [0092], substrate 122) from a light source (Fang, FIG. 1, laser 151) to induce a plasmonic wave (Fang, FIG. 2B, [0092], “The plasmon then creates an evanescent wave field that extends into the medium on either side of the gold film 122b”) at least proximal to a first surface of the substrate (Fang, FIG. 2B, [0092], gold film 122b), which first surface comprises a population of particles connected to the first surface via one or more first biomolecules (Fang, [0076], “single particle orientation and rotational tracking (SPORT) of plasmonic nanoparticles in various chemical and biological systems,” and [0097], “The stability of a microscopy imaging system is very critical for precisely recovering biological, chemical events especially when it requires to record the data for long period”); and,
detecting a change in position … of the particles in the population along at least three dimensions substantially simultaneously to generate statistics in a single measurement (Fang, [0098], “FIG. 5B shows a design of a multi-modality, multi-color, 4-channel imaging module that can enable the 3D single particle tracking capability through bifocal imaging or point spread function (PSF) engineering such as parallax imaging, double-helix PSF, astigmatism, etc.”), which three dimensions comprise two substantially lateral dimensions and an axial dimension, from a change in intensity of the incident light reflected at an interface of the first surface of the substrate using the SPRM device (Fang, [0090], “The ratio of fluorescence intensities from sequential acquisitions with fixed-angle TIRFM and wide-field microscopy [65-66] or from two-angle TIRFM [67-70] can give good estimates of axial distances, while more depth-resolved information is obtainable with prism or objective-based variable-angle TIRFM [62, 7-74] where a stack of multi-angle images contains the integrated fluorescence intensity over various thicknesses of the sample”).
Fang discloses the above but does not explicitly disclose:
… detecting a change in position of 100 or more of the particles…
However, Fang discloses particle detection in [0098] and Examiner previously cited [0083]:
The coupling of the Raman and DIC spectroscopy allows us to correlate the surface enhancement and inter-particle distance information.” (Examiner notes for Fang to determine inter-particle distance information, Fang would inherently be tracking information related to two or more particles.)
Pursuant to MPEP 2144.04(VI)(B) – Duplication of Parts:
[T]he court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced.
Fang discloses disclosure of multiple particles, but does not explicitly disclose “100 or more” particles. PHOSITA would be aware of how to add additional means for detection of additional particles. Based on Examiner’s review of the specification and prior art, the additional means for detection of additional particles would not introduce any new or unexpected results. Therefore, it would have been obvious to PHOSITA before Applicant’s filing date to include additional means of detection of additional particles and would require routine skill in the art.
Regarding Claim 21, Fang discloses Claim 1, and Fang further discloses:
… wherein one or more members of the population of particles are connected to the first surface via more than one biomolecule (Fang, [0076], “single particle orientation and rotational tracking (SPORT) of plasmonic nanoparticles in various chemical and biological systems,” and [0097], “The stability of a microscopy imaging system is very critical for precisely recovering biological, chemical events especially when it requires to record the data for long period”).
Regarding Claim 22, Fang discloses Claim 1, and Fang further discloses:
… comprising detecting specific and/or non-specific interactions of the first biomolecules with one or more other biomolecules (Fang, [0005], “Optical microscopy imaging has been playing an increasingly important role in the investigations of nanomaterials and biomaterials and fundamental chemical processes (e.g., diffusion, adsorption and reaction) at the molecular and nanoscale level”).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHAD A REVERMAN whose telephone number is (571)270-0079. The examiner can normally be reached Mon-Fri 9-5 EST.
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/CHAD ANDREW REVERMAN/Examiner, Art Unit 2877
/Kara E. Geisel/Supervisory Patent Examiner, Art Unit 2877
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