Prosecution Insights
Last updated: October 04, 2026
Application No. 18/294,701

INTERFEROMETRIC SCATTERING MICROSCOPY

Final Rejection §103
Filed
Feb 02, 2024
Priority
Aug 02, 2021 — GB 2111102.6 +1 more
Examiner
PHILLIPS, RUFUS L
Art Unit
2877
Tech Center
2800 — Semiconductors & Electrical Systems
Assignee
Refeyn Ltd.
OA Round
2 (Final)
63%
Grant Probability
Moderate
3-4
OA Rounds
5m
Est. Remaining
95%
With Interview

Examiner Intelligence

Grants 63% of resolved cases
63%
Career Allowance Rate
224 granted / 358 resolved
-5.4% vs TC avg
Strong +32% interview lift
Without
With
+32.1%
Interview Lift
resolved cases with interview
Typical timeline
3y 1m
Avg Prosecution
27 currently pending
Career history
386
Total Applications
across all art units

Statute-Specific Performance

§101
1.5%
-38.5% vs TC avg
§103
59.0%
+19.0% vs TC avg
§102
14.8%
-25.2% vs TC avg
§112
18.2%
-21.8% vs TC avg
Black line = Tech Center average estimate • Based on career data from 358 resolved cases

Office Action

§103
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 . Response to Arguments Applicant’s amendments overcome the previous rejections. Therefore, the previous rejections have been withdrawn. However, upon further search and consideration, a new rejection has been made based on newly found prior art (see prior art rejection below). 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. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) f or any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claims 20-22, 24, 27-28, 40, 43, 45, and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over Kukura (US 20190004299 A1) in view of Ramachandra (Fluorescence correlation spectroscopy: Simulations and Bio-Chemical Applications based on Solid Immersion Lens Concept), Yang (US 20230168484 A1), and Daugharthy (US 20220016624 A1). Regarding claim 20, Kukura teaches a method for measuring a property of an object, the method comprising providing a sample holder (2; paragraph 40) in a first sample solution including a first object (paragraph 97), such that the first object interacts with a surface of the sample holder (paragraphs 104, 90, 40); illuminating the surface of the sample holder (figure 1); detecting the scattered light from the first object interacting with the surface using an interferometric scattering microscope (figure 1; paragraphs 103-104); and measuring a property of the object using the detected scattered light (paragraphs 101-106 and 16). PNG media_image1.png 662 510 media_image1.png Greyscale Figure 1 of Kukura doesn’t explicitly illustrate the above “sample holder” is a “solid immersion lens.” However, in the specification, Kukura teaches that the sample holder can comprise a solid immersion lens and that this provides the benefits of higher magnification and higher numerical aperture (paragraph 63; claims 10-11). It’s noted that this implies illuminating the surface of the solid immersion lens (figure 1 and paragraph 63). Additionally, like Kukura (and like Applicant), Ramanshandra is directed to a method for optically measuring a property of an object using solid immersion lenses and teaches providing a solid immersion lens (solid immersion lens and SIL in section 3.3 and figure 3.4) in a sample solution (liquid dye in section 3.3 and sample dye sample in figure 3.4) comprising the object (fluorescence labelled molecules on page vi and dye labelled molecules and fluorescing molecules in sections 3.2-3.3) , such that the object interacts with a surface of the solid immersion lens (The objects in the liquid sample are on the planar surface of the solid immersion lens (SIL) and therefore there are many interactions including the interactions involved in the solid immersion lens providing support to hold the objects in the measurement region (section 3.3 and figure 3.4; section 3.3. explains that the objects [the molecules] are in a dye that is disposed directly on the solid immersion lens); illuminating the surface of the solid immersion lens (figure 3.4). Additionally, Ramanshandra teaches that the solid immersion lens provides the benefit of good collection light efficiency. PNG media_image2.png 774 786 media_image2.png Greyscale It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify figure 1 of Kukura such that the sample holder is a solid immersion lens (in other words, such that the method comprises providing a solid immersion lens in a sample solution comprising the object, such that the object interacts with a surface of the solid immersion lens; illuminating the surface of the solid immersion lens) – in order to achieve higher magnification, higher numerical aperture, and good collection efficiency. The above combination doesn’t explicitly teach dipping the solid immersion lens; withdrawing the dipped solid immersion lens from the sample solution; cleaning the withdrawn solid immersion lens such that the object is removed from the surface of the solid immersion lens; and dipping the solid immersion lens in a second sample solution including a second object, such that the second object interacts with a surface of the solid immersion lens. Like Kukura (and like the present application), Yang is directed to an interferometric scattering microscope (paragraph 11) and teaches dipping the objective lens (paragraph 39; figure 8A). Additionally, Yang teaches this is an equivalent to immersion and that the immersion objective is a dipping objective (paragraphs 139-143). Similarly, like Kukura (and like the present application), Daugharthy is directed to measuring samples through objective lenses and teaches that dipping objective lenses provides the benefit of higher image quality “by eliminating the refractive index mismatch occurring at the interface between two media with distinct refractive indexes, such as an air-water interface or water-glass interface (paragraph 145).” PNG media_image3.png 716 716 media_image3.png Greyscale It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the method comprises dipping the solid immersion lens because dipping is an art recognized equivalent and in order to achieve the benefits of higher image quality (also see Thiele in additional prior art which teaches dipping immersion lenses into the sample solution). The above combination doesn’t explicitly teach withdrawing the dipped solid immersion lens from the sample solution; cleaning the withdrawn solid immersion lens such that the object is removed from the surface of the solid immersion lens; and dipping the solid immersion lens in a second sample solution including a second object, such that the second object interacts with a surface of the solid immersion lens. As mentioned above, like Kukura (and like the present application), Daugharthy is directed to measuring samples through objective lenses. Daugharthy teaches withdrawing the dipped objective lens from the sample solution (implied by the fact that Daugharthy teaches dipping into the sample solution and then cleaning, this implies to one of ordinary skill in the art withdrawing the lens from the sample solution in order to perform the cleaning); cleaning the withdrawn solid immersion lens such that the object is removed from the surface of the solid immersion lens (paragraph 149); and dipping the objective lens in a second sample solution including a second object, such that the second object interacts with a surface of the objective lens (suggested by the fact that Daugharthy teaches cleaning the objective lens in order to improve imaging, which suggests that it will be used again to image another sample; paragraph 149). Additionally, Daugharthy teaches this provides the benefit of improving imaging (paragraph 149). It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the method comprises withdrawing the dipped solid immersion lens from the sample solution; cleaning the withdrawn solid immersion lens such that the object is removed from the surface of the solid immersion lens; and dipping the solid immersion lens in a second sample solution including a second object, such that the second object interacts with a surface of the solid immersion lens – in order to improve imaging while making multiple measurements. Regarding claim 21, Kukura teaches measuring a property of the object includes quantifying the mass of the object (paragraphs 101-106 and 16). Regarding claim 22, Kukura teaches the measuring a property of the object includes measuring or quantifying a change in the mass of an object (paragraphs 16 and 98-99). Regarding claim 24, the above combination doesn’t explicitly teach the step of flowing air over the solid immersion lens. However, in the combination above, the method comprises cleaning the solid immersion lens. Additionally, Kukura teaches the step of flowing air over the elements of the device that have been clean in order to dry the elements (paragraph 154). It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above method so that it comprises the step of flowing air over the solid immersion lens in order to dry the solid immersion lens after it has been cleaned. Regarding claim 27, Kukura teaches the illuminating light is spatially and temporally coherent (paragraph 12). Regarding claim 28, Kukura teaches the object is a protein, a lipid, a carbohydrate, an organic polymer, a nucleic acid, molecule, a virus, a vesicle, an assembly complex, or a virus-like particle (paragraph 71). Regarding claim 40, in the above combination, the cleaning of the solid immersion lens includes dipping the solid immersion lens into at least one cleaning solution (Daugharthy, paragraph 149). Regarding claim 43, Kukura doesn’t explicitly teach the first sample solution and the second sample solution are disposed in respective wells of a multi-well plate. Like Kukura (and like the present application), Yang is directed to an interferometric scattering microscope (paragraph 11) and teaches that multi-well plates are standard specimen mounting techniques (paragraph 11) and “if specimens are disposed in wells of a multi-well plate, the specimens can be imaged sequentially” (paragraph 82). It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the first sample solution and the second sample solution are disposed in respective wells of a multi-well plate in order to measure a plurality of samples sequentially, while having a compact system. Regarding claim 45, Kukura teaches at least a portion of the solid immersion lens is hemispherical or superhemispherical (paragraph 63). Regarding claim 47, Kukura teaches the interferometric scattering microscope further comprises a spatial filter (20; paragraphs 3 and 54). Regarding claim 48, the above combination comprises illuminating the surface of the solid mmersion lens; detecting the scattered light from the second object interacting with the surface using the interferometric scattering microscope; measuring a property of the second object using the detected scattered light (since it comprises conducting a second measurement in the same ways as the first measurement). Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Kukura, Ramachandra, Yang, and Daugharthy as applied to claim 20 above, and further in view of Castellarnau (US 20150253237 A1). Regarding claim 25, Kukura doesn’t explicitly teach the step of applying a plasma to the surface of the solid immersion lens. However, in the above combination, the solid immersion lens acts as the sample support/holder (see the section regarding claim 20, above). Like Kukura (and like Applicant), Castellarnau is directed to a method for optically measuring a property of an object and teaches the step of applying a plasma to the surface of a sample support/holder (paragraph 113). Additionally, Castellarnau teaches it provides the benefit of sterilizing the sample support/holder(paragraph 113). It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the method comprises the step of applying a plasma to the surface of the solid immersion lens in order to sterilize the solid immersion lens. Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Kukura, Ramachandra, Yang, and Daugharthy as applied to claim 20 above, and further in view of Connolly (US 20190264264 A1). Regarding claim 26, Kukura doesn’t explicitly the step of functionalising the surface of the solid immersion lens. However, Kukura teaches that the method can be modified to include a step of functionalizing and that this provides the benefit of targeted detection in the presence of other analytes (paragraph 114). Additionally, Connolly is directed to a method of optically measuring a property of an object , including proteins, and provides a general teaching the step of functionalizing the surface (paragraph 47), where the surface is the support of the sample (figure 7). It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the method comprises the step of functionalising the surface of the solid immersion lens (which is the support of the above combination) in order to achieve targeted detection in the presence of other analytes. Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Kukura, Ramachandra, Yang, and Daugharthy, as applied to claim 20 above, and further in view of Yarden (US 20200333242 A1). Regarding claim 41, the above combination doesn’t explicitly teach the cleaning solution includes at least one of an alcohol or an acid. Like the above combination (and like the instant application), Yarden is directed to the problem of cleaning lenses in optical measurement systems and teaches the cleaning solution includes at least one of an alcohol or an acid (paragraph 40). It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the cleaning solution includes at least one of an alcohol or an acid in order to use cleaning supplies that are known to work for lenses and in order to provide disinfectant properties. Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Kukura, Ramachandra, Yang, and Daugharthy, as applied to claim 20 above, and further in view of Mao (US 20190308190 A1). Regarding claim 42, the above combination doesn’t explicitly teach cleaning solution includes at least one of an ethanol, an isopropanol, a hydrochloric acid, or a sulphuric acid. However, Daugharthy teaches that having a cleaning solution includes at least one of an ethanol, an isopropanol, a hydrochloric acid, or a sulphuric acid provides the benefit of cleaning and removing objects that are not of interest (paragraphs 78 and 169). Additionally, like the above combination (and like the instant application), Mao is also directed to microscopes and concerned with the problem of cleaning objective lenses and teaches cleaning solution includes at least one of an ethanol, an isopropanol, a hydrochloric acid, or a sulphuric acid (paragraph 141). It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the cleaning solution includes at least one of an ethanol, an isopropanol, a hydrochloric acid, or a sulphuric acid in order to effectively remove objects that are not of interest and therefore provide a thorough cleaning. Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Kukura, Ramachandra, Yang, and Daugharthy, as applied to claim 20 above, and further in view of Kawata (US 2014/0002905) Regarding claim 44, the above combination doesn’t explicitly teach the solid immersion lens is mounted in a lens assembly. Like the above combination (and like the instant application), Kawata is directed to an optical microscope and teaches the objective lens is mounted in a lens assembly (paragraph 34). Additionally, Kawata teaches this provides the benefit of allowing one to choose the desired objective (paragraph 34) It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the solid immersion lens is mounted in a lens assembly in order to increase the flexibility of the system by having a variety of objectives to choose from. Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Kukura, Ramachandra, Yang, and Daugharthy, as applied to claim 20 above, and further in view of Ghislain (US 5,939,709) Regarding claim 46, the above combination doesn’t explicitly teach the solid immersion lens material includes at least one of diamond, zirconia, sapphire, lithium niobate, or glass.. Like the above combination (and like the instant application), Ghislain is directed to an optical measurement device comprising a solid immersion lens and teaches the solid immersion lens material includes at least one of diamond, zirconia, sapphire, lithium niobate, or glass (zirconia and glass in column 9, lines 5-15). Additionally, Ghislain teaches choosing the material based on the refractive index, hardness, and ability to take a polish (column 9, lines 5-15). It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the solid immersion lens material includes at least one of diamond, zirconia, sapphire, lithium niobate, or glass in order to select the right material for the needed refractive index, hardness, and ability to take a polish. Additional Prior Art US 6 280 960 B1, which discloses a solid immersion lens (7; column 7, lines 50-55), illuminations, and detection (figure 1), and an interferometric scattering microscope (another embodiment mentioned in column 1, lines 29-32). PNG media_image4.png 576 646 media_image4.png Greyscale US 20050063046 A1 reads, “Therefore, it is possible to bring the solid immersion lens into optically-close contact with the sample … In the present invention, "optical close contact" means a state where the solid immersion lens is optically coupled to the sample through evanescent coupling.” (paragraphs 18-19) US 20100202041 A1 Reads, “ In the case in which an observation object is observed by use of the observation apparatus of the present invention, the solid immersion lens held by the solid immersion lens holder is caused to contact closely with the observation object” (paragraph 8) US 20240011885 A1 reads, “[0151] It should be noted that SIL optical elements can be fabricated with facets on the flat, so that only a small central area truncating the facets exists at the center and projects outward from the SIL. This is helpful for positioning a SIL to an object and assuring there is close contact with the surface, even if the object is not completely flat.” Arata (US 20080158667 A1) is directed to optical measurements and concerned with solid immersion lenses and teaches providing a solid immersion lens in a sample solution comprising the object, such that the object interacts with a surface of the solid immersion lens; and illuminating the surface of the solid immersion lens; Thiele (EP 2284541 A1) discloses “The objective was a Zeiss Plan-APOCHROMAT 63x/NA1.0 VIS/IR water immersion lens directly dipping into the cell culture dish, heated to 37°C.” Luscher (US 20100328664 A1) reads, “an immersion fluid 172 in which the objective lens 144 is immersed (Fig. 10), or a dipping fluid 160 in which the objective lens 144 is dipped (Fig. 11 )” (paragraph 74) PNG media_image5.png 296 338 media_image5.png Greyscale PNG media_image6.png 308 382 media_image6.png Greyscale Luscher2 (US 20090325217 A1) reads, “Alternatively, the objective lens 142 may be a water-dipping lens in situations in which there is no need to correct for refraction caused by the wall 268A, such as when the wall 268A is formed of a material with a refractive index similar to or the same as the fluid 278.” (paragraph 110). US 20150253355 A1 reads, “an SIL (solid immersion lens) in the optical path of the NV centre. The SIL might be processed in the diamond, or be a separate diamond SIL attached” (paragraph 161) Yamaguchi (US 20220244163 A1) is directed to a method for optically measuring a property of an object using light scattering and teaches the step of cleaning surfaces of the measurement device in direct contact with the object such that the object is removed from the surface (paragraphs 10, 54, and 58). Additionally, Yamaguchi teaches this provides the benefit of removing the sample still adhering to the surfaces (paragraphs 10, 54, and 58). Conclusion THIS ACTION IS MADE FINAL. 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUFUS L PHILLIPS whose telephone number is (571)270-7021. The examiner can normally be reached M-Th, 2 -10 pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michelle Iacoletti can be reached at (571) 270-5789. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /RUFUS L PHILLIPS/Examiner, Art Unit 2877
Read full office action

Prosecution Timeline

Feb 02, 2024
Application Filed
Jan 15, 2026
Non-Final Rejection mailed — §103
Jul 01, 2026
Examiner Interview Summary
Jul 13, 2026
Response Filed
Sep 16, 2026
Final Rejection mailed — §103 (current)

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Prosecution Projections

3-4
Expected OA Rounds
63%
Grant Probability
95%
With Interview (+32.1%)
3y 1m (~5m remaining)
Median Time to Grant
Moderate
PTA Risk
Based on 358 resolved cases by this examiner. Grant probability derived from career allowance rate.

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