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 § 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:
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.
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) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 65-77, 79-81 and 83 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (US 2021/0041683) (“Huang”), and further in view of Falk et al. (US 2021/0018740)(“Falk”) and Hedde et al. (US 2019/0353884)(“Hedde”).
With regards to claim 65, Huang discloses a microscopy system (Abstract; FIG. 1) comprising:
a plurality of containers comprising a plurality of samples ([0033]; “The cells were placed in a 96-well plate and different wells were treated with different concentrations of Cytochalasin D (CD),…”)([0031]; 8-well chamber), wherein each sample of the plurality of samples comprises a distribution of fluorescent particles ([0030][0043]; 45 nm fluorescent beads);
an collimated illumination source (light source 14)([0037];”The illumination light came from three lasers…”) configured to emit a collimated beam along a beam path [0037]; “The beams …, collimated by a telescope composed of two achromatic lens,…”, ;
a set of optical elements positioned along the beam path and configured to elongate the collimated beam along an axis ([0037]; “The beams were … expanded by two cylindrical lenses…to form an elongated shape,… The full-width at half-maximum (FWHM) of the Gaussian and Bessel beams were respectively 730 nm and 554 nm along the z′ axis, 12.8 µm and 18.6 µm along the x′ axis.”); and
a translating stage ([0023]; translation stage 1 and 2), wherein the system is configured to scan a set of cross- sections of each sample of the subset of the plurality of containers [0023][0040].
Huang discloses a reservoir 28 comprising a transparent side (window 34) through which light from the beam path is configured to enter ([0028]; “The second opening 32, however, incorporates a window 34 that prevents the liquid from exiting the reservoir 28 and that enables light to travel to the third objective O3, which is immersed in the liquid. In some embodiments, the second window 34 can comprise a coverslip or other transparent sheet through which the light can pass.”). Also, the reference teaches of 8-well coverglass-bottomed chambers [0031] that contains fluorescent samples/beads [0031][0031]. Finally, the reference teaches that small tubes or cylinders of agarose gel can be used to hold the sample in a tight focal space of objective lenses [0003].
Huang do not disclose;
a distribution of fluorescent particles that is contained within a respective container of the plurality of containers;
a reservoir comprising a set of transparent sides through which light from the beam path is configured to enter;
a tube holder configured to retain a subset of the plurality of containers in position within the reservoir;
a translating stage configured to translate the tube holder along a translation axis through light from the beam path.
In the same field of endeavor, Falk discloses a microscope comprising the sample holder and a method for imaging a plurality of samples with said microscope [0001], comprising;
a tube holder ([0052]; tube support 10) configured to retain a subset of the plurality of containers ([0052]; “One or more of the elongated sample tubes 15, which accommodate the plurality of samples 16 to be imaged, are arranged on a tube support 10. In one aspect, the one or more elongated sample tubes 15 are arranged on the tube support 10 substantially in parallel to each other, e.g. along a substantially vertical direction. The arrangement of the plurality of sample tubes 15 on the tube support 10 enables parallel imaging of the plurality of samples 16.”)([0076]; tube rack or magazine 14) in position within a reservoir ([0087]; “The sample holder 5, the tube rack 14, … may be arranged in a chamber…”); and
a translating stage ([0050]; stage 11) configured to translate the tube holder along a translation axis through light from the beam path ([0050][0074];)3
In view of Falk, it would have been obvious to one of ordinary skill within the art before the effective filing date of the claimed invention to modify the system of Huang with a tube support, a sample holder and a tube rack and a stage that can position the components within a reservoir/chamber and also can translate the plurality of tubes into a beam path for imaging. The motivation it to position the sample tubes for parallel imaging.
The references do not specifically disclose a distribution of fluorescent particles contained within a container of the plurality of containers and a reservoir comprising a set of transparent sides through which light from the beam path is configured to enter
In the same field of endeavor, Hedde discloses a selective plane illumination microscopy [0001] that has fluorescence lifetime measurement capability [0007] and utilizes a two-window sample chamber (Abstract). Hedde teaches of evaluating fluorescent beads contained within a two window sample chamber [0037][0124] wherein the chamber can be a multiwell chamber [0027][0032][0043]. Further, [0151] teaches “…since the size of the individual wells can be very small as opposed to designs that require optics dipping into the sample chamber, a large number of wells can be accommodated within the same chamber to allow for automated, high throughput three-dimensional time course imaging with sideSPIM.” Finally, the two window sample chamber comprises of two optically transparent windows that allows illumination light to be introduced to the chamber (having fluorescent beads within) from the sides [0055].
In view of Hedde, it would have been obvious to one of ordinary skill within the art before the effective filing date of the claimed invention to have the fluorescent beads/particles distributed in the wells of a two window sample chamber wherein the two window chamber allows illumination light from the side. The motivation is to gain and allow automated three-dimensional imaging of fluorescent beads/particles that are distributed within a multi-well two window sample chamber.
With regards to claim 66, modified Huang discloses the system of claim 65, wherein the set of transparent sides comprises a first transparent side and a second transparent side connected to the first transparent side at a right angle. ([0094]; “With two optically transparent windows perpendicular to each other,…”)
With regards to claim 67, modified Huang discloses the system of claim 66, wherein the translation axis is orientated at an angle relative to the first transparent side and the second transparent side and parallel to the of the subset of the plurality of containers retained by the tube holder. (Falk; [0065][0074][0079] in view of the rejection of claim 65)
With regards to claim 68, modified Huang discloses the system of claim 65, wherein the plurality of samples comprises at least 96 samples. (Huang; “The cells were placed in a 96-well plate…”)
With regards to claim 69, modified Huang discloses the system of claim 65, wherein the plurality of samples comprises at least 20 samples. (Huang; “The cells were placed in a 96-well plate…”)
With regards to claim 70, modified Huang discloses the system of claim 65, wherein the set of optical elements comprises:
a first cylindrical lens (Huang; FIG. 1; [0023]; CL3) positioned in the beam path and configured to collimate the beam along a single axis (Huang; [0037]; “The beams were combined by two dichroic mirrors, collimated by a telescope composed of two achromatic lens, …”), thereby producing a collimated beam having a short axis orthogonal to a direction of propagation and long axis orthogonal to the short axis and the direction of propagation (Huang; [0037]; and
a second cylindrical lens (Huang; FIG. 1; [0023]; CL2) positioned in the beam path after the first cylindrical lens and configured to focus the collimated beam along the short axis to a focal plane (Huang; [0037][0039]).
With regards to claim 71, modified Huang discloses the system of claim 65, wherein a sample of the plurality of samples comprises a three-dimensional sample containing a distribution of fluorescent molecules. (see the rejection of claim 65)
With regards to claim 72, modified Huang discloses the system of claim 65, further comprising a detector configured to detect fluorescent light from each sample. (Huang; [0024]; image sensor 22)
With regards to claim 73, modified Huang discloses the system of claim 65, wherein the reservoir contains an index matching fluid. (Hedde; [0063][0095])
With regards to claim 74, modified Huang discloses the system of claim 65, wherein a sample of the plurality of samples comprises a distribution of protein molecules. (Huang; [0016][0055]; mRFP-actin)
With regards to claim 75, modified Huang discloses a method comprising:
transmitting a plurality of containers comprising a plurality of samples through a beam path (see the rejection of claim 65),
wherein each sample of the plurality of samples comprises a distribution of fluorescent particles and is contained within a respective container of the plurality of containers (see the rejection of claim 65),
wherein the beam path is generated from a collimated illumination source configured to emit a collimated beam through a set of optical elements configured to elongate the collimated beam along an axis (see the rejection of claim 1), and
wherein transmitting comprises retaining the plurality of containers within a tube holder positioned within a reservoir, the reservoir comprising a set of transparent sides through which light from the beam path is configured to enter (see the rejection of claim 1);
producing a dataset upon detecting fluorescent light emitted from each of the plurality of samples (Huang; [0014][0045][0045])(Hedde; [0135]); and
from the dataset, quantifying targets of the plurality of samples upon identifying a subset of fluorescent particles conforming to a shape (Hedde; [0120]).
With regards to claim 76, modified Huang discloses the method of claim 75, wherein a sample of the plurality of samples comprises a distribution of protein molecules. (Huang; [0016][0055]; mRFP-actin)
With regards to claim 77, modified Huang discloses the method of claim 75, wherein a sample of the plurality of samples comprises a three-dimensional sample containing a distribution of fluorescent molecules. (see the rejection of claim 65)
With regards to claim 79, modified Huang discloses the method of claim 75, wherein the set of optical elements comprises:
a first cylindrical lens (Huang; FIG. 1; [0023]; CL3) positioned in the beam path and configured to collimate the beam along a single axis (Huang; [0037]; “The beams were combined by two dichroic mirrors, collimated by a telescope composed of two achromatic lens, …”), thereby producing a collimated beam having a short axis orthogonal to a direction of propagation and long axis orthogonal to the short axis and the direction of propagation (Huang; [0037]; and
a second cylindrical lens (Huang; FIG. 1; [0023]; CL2) positioned in the beam path after the first cylindrical lens and configured to focus the collimated beam along the short axis to a focal plane (Huang; [0037][0039]).
With regards to claim 80, modified Huang discloses the method of claim 75, wherein the plurality of samples comprises at least 20 samples. (Huang; “The cells were placed in a 96-well plate…”)
With regards to claim 81, modified Huang discloses the method of claim 75, wherein transmitting comprises translating the tube holder along a translation axis through light from the beam, using a translation stage coupled to the tube holder. (see the rejection of claim 65)
With regards to claim 83, modified Huang disclose the method of claim 75, wherein quantifying targets comprises removing asymmetric particles from a plurality candidate particles represented in the dataset. (Hedde; [0135])
Allowable Subject Matter
Claims 78, 82 and 84 are 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.
The following is a statement of reasons for the indication of allowable subject matter:
With regards to claim 78, modified Huang discloses the method of claim 75, wherein identifying a subset of fluorescent particles comprises applying a machine learning algorithm with a set of semi-supervised labels comprising a signal intensity label and a polydispersity label.
With regards to claim 82, modified Huang do not disclose the method of claim 75, wherein quantifying targets of the plurality of samples comprises identifying signal positive particles from the dataset, wherein the signal positive particles have intensities greater than the intensity threshold condition.
With regards to claim 84, modified Huang disclose the method of claim 75, further comprising moving light from the collimated illumination source relative to a sample of the plurality of samples, with movements ranging from 0.1 kHz to 20 kHz.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
True (US 2009/0149340)
Durack et al. (US 2005/0112541)
Tafas et al. (US 2021/0252518)
Keller et al. (US 2019/0219811)
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HUGH H MAUPIN whose telephone number is (571)270-1495. The examiner can normally be reached M-F 7:30 - 5:00 pm.
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/HUGH MAUPIN/Primary Examiner, Art Unit 2884
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