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 Amendment
The Amendment filed 05/13/2026 has been entered. Claims 15, 17-20, 23-24 and 26-33 remain pending and are being examined herein.
Status of Objections and Rejections
All rejections of claims 21, 22 and 25 and are obviated by Applicant’s cancellation.
The objection to the drawings has been withdrawn in view of Applicant's amendment.
The objection to the specification is maintained because the amendment does not address the issue relating to para. 0065.The objection to the claim has been withdrawn in view of Applicant's amendment.
The rejection of claims 15 and 17-33 under 35 U.S.C 112(a) and 35 U.S.C 112(b) are being withdrawn in view of Applicant’s amendment.
The rejection under 35 U.S.C. 103 is being withdrawn in view of Applicant’s amendment.
New grounds for rejection under 35 U.S.C. 103 are necessitated by Applicant’s amendments.
Specification
The disclosure is objected to because of the following informalities:
para. 0065 states, “…microdroplet b is a micron-sized droplet (a diameter of the droplet is 10 mm to 50 mm”, and Para. 00107 states, “Referring to FIG. 14, which is an image of microdroplets (microdroplets b)…” which is not consistent with the image shown in Fig. 14. Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
“second sealing member” in claim 29; and
“first sealing member” in claim 32.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
In this instant case,
“second sealing member” in claim 29 has a corresponding structure of elastomer (para. 0083) and equivalents thereof; and
“first sealing member” in claim 32 a corresponding structure of elastomer and equivalents thereof (para. 0083).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 15, 24, 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Leblanc et al. (US 20120244043) in view of Link (US 20120309002).
Regarding claim 15, Leblanc teaches a sample analysis system (the device shown in Figs. 9-16, paras. 124-129; para. 0129, the device correspond to Configuration 1) comprising:
a liquid inlet and outlet device applying flow cell comprising:
a flow cell (Figs. Fig. 9) comprising:
a first cover (bottom plate)(para. 0016);
a second cover (top plate, para. 0016) facing the first cover (Fig. 9B);
a spacer (first gasket)(paras. 0124 and 0126, Fig. 8).
Leblanc. teaches a microfluidic device that gaskets to provide a reliable seal between a substrate of the device and the fluid transport mechanism (e.g. pipette, tubing and other conduit). Leblanc teaches the device in Figs. 9-16 corresponds to Configuration 1 (para. 0129), which comprises a top carrier, a first gasket, a top plate and a bottom plate. Leblanc. teaches the first gasket (spacer) has three bosses for the three inlet ports (Fig. 8A , 8C and 9B, para. 0126), and the first gasket is positioned between the top carrier and the top plate (Fig. 9B, para. 0116), and thus fails to teach at least two spacers provided side by side between the first cover and the second cover, wherein both sides of each of the at least two spacers are in contact with the first cover and the second cover.
However, Leblanc teaches the microfluidic device can be assemble in a variety of configurations, including Configuration 3 (paras. 0115, 0118). Leblanc teaches in Configuration 3 does not include a carrier, and that the gasket is contained between the top plate and bottom plate (Figs. 7A-7D). Leblanc further teaches for each port there is an individual gasket of a single boss (Figs. 7B). Leblanc teaches Configuration 3 has an overall decreased thickness as compared to Configuration 1, and allow for other features to be designed into the device to protect sensitive areas such as an imaging FOV (0118).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted Configuration 1 as the assembling configuration for the microfluidic device taught by Fig. 9-16 of Leblanc with Configuration 3 that does not include the top carrier and have the gasket layer be contained between the top plate and the bottom plate as taught by para. 0118 and Fig. 7A-D of Leblanc in order to an overall decreased thickness of the device and allow for other features to be designed into the device to protect sensitive areas such as an imaging FOV (para. 0018) with a reasonable expectation of success (MPEP 2143)(I)(G). In addition it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the first gasket with three bosses taught by Leblanc in the embodiment of Fig. 8-16 with three gaskets each with one boss for the each inlet port as taught by Fig. 7 of Leblanc because one of ordinary skill in the art would accordingly have recognized the whether one gasket with three bosses or three gaskets each with one boss would result in the predictable result of providing a gasket boss for each port for reliable sealing required for the inlet ports (para. 0109, Figs. 7B and 8A-C).
The teachings of modified Leblanc (Fig. 9B assembled with Configuration 3 and have gaskets of 1 boss instead of 1 gasket of 3 bosses) yields to teach at least two spacers (the gasket with one boss that corresponds to the middle inlet and the gasket with one boss that corresponds to the left inlet port provided side by side between the first cover and the second cover, wherein both sides of each of the at least two spacers are in contact with the first cover and the second cover (para. 00118, Figs. 7B).
Modified Leblanc teaches adjacent two of the at least two spacers cooperatively form a flow path (the flow path that connects the left and middle inlets through the main channel, para. 0096).
Modified Leblanc a surface of the first cover facing the second cover forms a detection surface (the channel surface of the bottom plate, which is the first cover, para. 0116).
Leblanc teaches the microfluidic device can be utilized for conducting numerous chemical and biological assays such as gene amplification and DNA sequencing (para. 0161), and the assays based on droplet (para. 0055). Leblanc teaches the device includes a combination of coalescence modules, detection modules, mixing modules to conduct assay. Leblanc further teach a main channel connect the inlets to the modules (paras. 0096- 0097 0150, 0152) such that samples can be entered through inlets and travel through the main channel to various modules for various process steps of the assay to be performed (para. 0056).
Modified Leblanc does not teach the specifics of the surfaces of the channels/modules that are required for the DNA sequencing assay and thus fails to teach the detection surface comprises plurality of active regions arranged in an array and a separation region excluding the plurality of active regions, the plurality of active regions is provided with chemical active groups configured to combine with a target or molecules to be tested in a first sample, none of the chemical active groups is provided on the separation region.
However, Link teaches a device for performing droplet based DNA sequencing assays (para. 0017 and 0034). Link further teaches performing DNA sequencing requires a flow cell/channel surface coated (para. 0076) with plurality of active regions arranged in an array and a separation region excluding the plurality of active regions, the plurality of active regions is provided with chemical active groups (clustered arrays of nucleic acid colonies, para. 0076-0077 and 0088) configured to combine with a target or molecules to be tested in a first sample, none of the chemical active groups is provided on the separation region (para. 0076).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the detection surface taught by Leblanc to include with plurality of active regions arranged in an array and a separation region excluding the plurality of active regions, the plurality of active regions is provided with chemical active groups (clustered arrays of nucleic acid colonies, para. 0076-0077 and 0088) configured to combine with a target or molecules to be tested in a first sample, none of the chemical active groups is provided on the separation as taught by link (para. 0076-007) because such modification provides a necessary component for the flow cell to perform DNA sequencing (Link, paras. 0076, 0088 and Leblanc, para. 0161) with a reasonable expectation of success (MPEP 2143)(I)(G).
Modified Leblanc further teaches the flow cell comprising:
a first opening (the middle inlet port, which is in the top plate in modified Leblanc, see Figs 9 and also Fig. 7B), communicating with each flow path (para. 0096), wherein the first opening is configured to inject the first sample of nanometer-sized into the flow cell (interpreted as a functional limitation. first sample is not positively recited. Moreover, Fig. 9B, the first opening is configured for a sample to be injected into the flow cell; and
a second opening (the left inlet port, which is in the top plate in modified Leblanc, see Figs 9 and also Fig. 7B), communicating with each flow path (para. 0069), wherein the first opening and the second opening of a same flow path are adjacent to two opposite ends of the flow path, respectively (the left and middle inlet ports are fluidically connected, and thus there is a flow path between the two inlet ports, wherein each inlet port is at the opposite end of that flow path. Furthermore the flow path can include the main channel, for instance, the flow path can have one end at the left inlet that leads to the main channel, go down to the main channel for a distance, then change/reverse direction toward the middle inlet), the second opening is configured to inject microdroplets of micron-size into the flow cell (para. 0096, “The inlet module generally comprises a junction between the sample inlet channel and the main channel such that a solution of a sample … is introduced to the main channel and forms a plurality of droplets”), the microdroplets comprise a second sample (the microdroplets are not positively recited, and thus this limitation does not further limit the structure of the claim).
Modified Leblanc does not explicitly teach wherein a hydraulic radius of the first opening is smaller than a hydraulic radius of the second opening.
However, Leblanc teaches wherein the port sizes are result-effective variable. Specifically, Leblanc teaches that a port size is customized based on the type of transport mechanism, e.g. various pipette tips or various size or tubing (para. 0111 and Fig. 5). Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). In addition, Leblanc teaches the device is for analyzing different types of samples (molecules, cells, small molecules or particles), and thus different transport mechanisms may be use for the different inlet port in order to accord different sample type.
Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the hydraulic radius of the first opening and the hydraulic radius of the second opening of Leblanc such that the hydraulic radius of the first opening is smaller than the hydraulic radius of the second opening because it would have been within the ambit of one of ordinary skill in the art to arrive at through routine experimentation.
Modified Leblanc fails to teach wherein the hydraulic radius of the second opening is 0.02 mm-0.2 mm.
Leblanc teaches wherein the port sizes (the hydraulic radius of the first and hydraulic radius second opening) are result-effective variables. Specifically, Leblanc teaches that the port size is customized based on the type of transport mechanism, e.g. various pipette tips or various size or tubing (para. 0111 and Fig. 5). Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). In addition, Leblanc teaches the device is for analyzing different types of samples (molecules, cells, small molecules or particles), and thus different transport mechanisms may be use for the different inlet port in order to accord different sample type.
Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the hydraulic radius the second opening of Leblanc such that the hydraulic radius of the second opening is 0.02 mm – 0.2 mm because it would have been within the ambit of one of ordinary skill in the art to arrive at through routine experimentation.
Modified Leblanc further teaches the liquid inlet and outlet device applying flow cell comprising:
a first joint device (pipette tip corresponding the middle inlet in Fig. 9B); and
a second joint device (tubing corresponding to the left inlet in Fig. 9B), wherein the first joint device is connected to the first opening, and the second joint device is connected to the second opening (Fig. 9B);
an upstream pump (pipette) connected to the first joint device (pipette tip), and configured to pump the first sample into the flow cell through the first joint device and the first opening (para. 0096), thereby causing the first sample to be adsorbed on the plurality of active regions of the detection surface arranged in an array (interpreted as an intended use. the first sample is not positively recited. A first sample can enter the device by pumping of the pipette, and subsequently, the sample can travel through main channel to the detection surface with an array of the active regions); and
Modified Leblanc teaches a tubing connected to the left inlet port (second opening)(Fig. 9B) which provides means for a sample to enter the microfluidic device, and the sample can be formed into droplets in the inlet module (para. 0096), and thus modified Leblanc fails to teach a microdroplet generating device configured to form microdroplets from the second sample and another upstream pump connected to the microdroplet generating device and the second joint device, and configured to pump the microdroplets into the flow cell through the second joint device and the second opening, thereby causing the microdroplets to be distributed in the flow path in an array.
However, Leblanc teaches droplets of a sample fluid can be formed within the inlet module on the microfluidic device or droplets can be formed before the sample fluid is introduced to the microfluidic device ("off chip" droplet formation)(para. 0082). Leblanc further teaches pumps are use to driving fluid flow.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the analysis system taught by Leblanc include a droplet generating device connected to the tubing of left inlet port and include an upstream pump as taught by Leblanc in para. 0082 and 0087 in order for droplets to be formed before the sample fluid is introduced to the microfluidic device and flow into the microfluidic device with a reasonable expectation of success (paras. 0082, 0087)(MPEP 2143)(I)(G).
Leblanc further teaches the analysis system comprises an optical imaging unit (microscope)(para. 0042) configured to capture an image of the flow cell (paras. 0042 and 0150).
Regarding claim 24, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 15.
Modified Leblanc fails to teach wherein the hydraulic radius of the first opening is 0.075 mm to 0.75 mm.
Leblanc teaches wherein the port sizes (the hydraulic radius of the first and hydraulic radius second opening) are result-effective variables. Specifically, Leblanc teaches that the port size is customized based on the type of transport mechanism, e.g. various pipette tips or various size or tubing (para. 0111 and Fig. 5). Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). In addition, Leblanc teaches the device is for analyzing different types of samples (molecules, cells, small molecules or particles), and thus different transport mechanisms may be use for the different inlet port in order to accord different sample type.
Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the hydraulic radius of the first opening of Leblanc to be 0.075 mm to 0.75 mm because it would have been within the ambit of one of ordinary skill in the art to arrive at through routine experimentation.
Regarding claim 26, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 15. Modified Leblanc further teaches wherein each of the at least two spacers is an adhesive layer (paras. 0015, 0049 and 0126, gasket is made from a silicone thermoplastic Genomier which has a contact adhesive).
Regarding claim 27, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 15. Leblanc further teaches wherein the first opening and the second opening are both on the .
Claims 17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Leblanc et al. (US 20120244043) in view of Link (US 20120309002) as applied to claim 15, and further in view of Jaffe et al. (US 20160123886 A1).
Regarding claim 17, modified Leblanc teaches the sample analysis system according to claim 15.
Leblanc teaches a microfluidic device comprising a detection module (optical imaging unit), where molecules, cells, small molecules or particles are to be detected, identified, measured or interrogated on the basis of at least one predetermined characteristic such as fluorescent labels (para. 0150 and 0175). Leblanc further teaches that the detection module includes a microscope (para. 0150).
Leblanc does not disclose the structure of the microscope and thus fails to explicitly teach wherein the optical imaging unit comprises a first lens assembly and a second lens assembly; the first lens assembly is configured to image the first sample; the second lens assembly is configured to image the microdroplets; a focal length of the first lens assembly is smaller than a focal length of the second lens assembly, and a field of view of the first lens assembly is smaller than a field of view of the second lens assembly.
However, Jaffe teaches an integrated fluorescence scanning system for imaging cells and fluorophore, etc. (paras. 0003 and 006). Jaffe teaches that system includes a microscope (170) that comprises two different objective lenses (410, 412) in order to provide different magnifications.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microscope of the detection module taught by Leblanc with a microscope that includes two objective lenses of different magnifications as taught by Jaffe in order to provide different magnifications with a reasonable expectation of success (Jaffe, para. 0068) (MPEP 2143)(I)(G). In addition, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have one of the objective lenses to have a higher magnification to image samples with molecules and selected the other objective lens to have a lower magnification to image samples with droplets in order to image different types of samples that are accommodated by the device of Leblanc (Leblanc, para. 0153) with a reasonable expectation of success (MPEP 2143)(I)(G).
The teachings of modified Leblanc would yield the optical imaging unit (microscope) comprises a first lens assembly (the objective lens with a higher magnification) and a second lens assembly (the objective lens of lower magnification); the first lens assembly is configured to image the first sample (interpreted as an functional limitation. The first sample is not positive recited. With the above modification, the first lens assembly has a higher magnification and is tailored for molecules); the second lens assembly is configured to image the microdroplets (interpreted as an functional limitation. With the above modification, the second lens assembly has a lower magnification and is tailor for molecules); a focal length of the first lens assembly is smaller than a focal length of the second lens assembly, and a field of view of the first lens assembly is smaller than a field of view of the second lens assembly (first lens assembly has a higher magnification and thus a smaller focal length and a smaller field view than that of the second lens assembly).
Regarding claim 19, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 17. Modified Leblanc further teaches wherein a magnification of the first lens assembly is greater than a magnification of the second lens assembly (see claim 17 above).
Regarding claim 20, modified Leblanc teaches the sample analysis system according to claim 15.
Leblanc teaches a microfluidic device comprising a detection module (optical imaging unit), where molecules, cells, small molecules or particles are to be detected, identified, measured or interrogated on the basis of at least one predetermined characteristic such as fluorescent labels (para. 0150 and 0175). Leblanc further teaches that the detection module includes a microscope (para. 0150).
Leblanc does not disclose the structure of the microscope and thus fails to explicitly teach wherein the optical imaging unit comprises a third lens assembly and a compensation lens assembly.
However, Jaffe et al. (US 20160123886 A1) teaches an integrated fluorescence scanning system for imaging cells and fluorophore, etc. (paras. 0003 and 006). Jaffe teaches that system includes a microscope (170) that comprises two different objective lenses (410, 412) in order to provide different magnifications.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microscope of the detection module taught by Leblanc with a microscope that includes two objective lenses of different magnifications as taught by Jaffe in order to provide different magnifications with a reasonable expectation of success (Jaffe, para. 0068) (MPEP 2143)(I)(G).
The teachings of modified Leblanc would yield wherein the optical imaging unit comprises a third lens assembly (one of the two objective lenses) and a compensation lens assembly (the other objective lens)(“compensation” is interpreted as an intended use. The objective lens meets the structural limitation of the intended use).
Claims 23 is rejected under 35 U.S.C. 103 as being unpatentable over Leblanc et al. (US 20120244043) in view of Link (US 20120309002) as applied to claim 15 and further in view of Fisher et al. (US 20220195519).
Regarding claim 23, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 15. Modified Leblanc teaches wherein a surface of the second cover facing the first cover forms another detection surface (the portion of the top plate surface that faces the channel surface of the bottom plate, Fig. 7B ).
Modified Leblanc teaches a surface of the first cover facing the second cover forms a detection surface (channel surface on bottom plate) includes arrays for chemical active regions for capturing oligonucleotide for DNA sequencing assay (claim 15, Link, para. 0076, 0088, clustered arrays of nucleic acid colonies), but does not teach the another detection surface also comprise arrays for chemical active regions, and thus fails to teach the another detection surface comprises plurality of active regions arranged in an array and a separation region excluding the plurality of active regions, the plurality of active regions of the another detection surface is provided with chemical active groups configured to combine with a target or molecules to be tested in the first sample, none of the chemical active groups is provided on the separation region of the another detection surface.
However, Fisher teaches a flow cell for conducting DNA sequencing assays (abstract). Fisher further teaches both the top and bottom flow cell surfaces include chemical active capture sites for the DNA sequencing assays (Fig. 2B, para. 0109-0111).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the another detection surface taught by modified Leblanc with a surface of chemical active capture sites as taught by (Fisher, Fig. 2B) where the plurality of active regions arranged in an array and a separation region excluding the plurality of active regions, the plurality of active regions of the another detection surface is provided with chemical active groups configured to combine with a target or molecules to be tested in the first sample, none of the chemical active groups is provided on the separation region of the another detection surface (Fisher, Fig. 2b and Link, para. 0076, 0088, clustered arrays of nucleic acid colonies) because one of ordinary skill in the art would accordingly have recognized a surface on the top surface of the flow cell surfaces comprises arrays of chemical active capture sites would result in the predictable result of providing suitable surface for DNA sequencing assay (Fisher, Fig. 2B, paras. 0109-0111; Link paras. 0076, 0088). See MPEP 2143)(I)(B). One of ordinary skill in the art would be motivated to make such of modification because of the modification would increase the number of capture sites to enough signal.
Claims 28-33 are rejected under 35 U.S.C. 103 as being unpatentable over Leblanc et al. (US 20120244043) in view of Link (US 20120309002) as applied to claim 15, and further in view of Stumbo et al. (US 20190002956 A1).
Regarding claim 28, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 15.
Modified Leblanc teaches the top plate comprises pockets that forms inlet ports, for the gasket to be molded into (para. 0118, Configuration 3).
Leblanc teaches in Fig. 9B, configuration 1, an addition plastic chip port that sits in each of the of the top plate pockets.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the inlet pockets of the top plate to have with an additional plastic chip port because one of ordinary skill in the art would accordingly have recognized the additional plastic chip port in the inlet port would result in the predictable result of providing an inlet port (Fig. 9).
Modified Leblanc teaches the second joint device (tubing and the corresponding plastic chip port) comprises a second joint portion (tubing), the second joint portion comprises a second joint (the opening of the tubing that is in the plastic chip port), the second joint is connected to the second opening (Fig. 9B)(a portion of the tubing is directly connected to the second opening, and thus the entire tubing is connected to second opening through that portion).
Leblanc teaches droplets are formed before the sample fluid is introduced to the microfluidic device (para. 0082). Modified Leblanc further teaches a device that generates droplets is connected to a tubing such that the droplets can be introduced into the microfluidic device (see claim 15). Modified does not teach the structure that transports the droplets from droplet generating device to the tubing and thus fails to teach wherein the second joint device comprises a second joint portion, the second joint portion comprises a first joint and a second joint, the second joint is connected to the second opening, the first joint is away from the second opening, a size of the first joint along a direction perpendicular to an extension direction of the flow path is smaller than a size of the second joint along the direction perpendicular to the extension direction of the flow path.
However, Stumbo teaches a fluid transporter for transporting droplets from a reservoir to a another location in a single file configuration. Stumbo teaches the fluid transporter includes a first joint (junction 106 to 74) and a second joint (outflow port 178), a size of the first joint along a direction perpendicular to an extension direction of the flow path of the droplet is smaller than a size of the second joint along the direction perpendicular to the extension direction of the flow path droplet (the diameter 74 is smaller than the diameter of 178).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the tubing of the Leblanc with the fluid transporter taught by Stumbo in order to transport droplets from the droplet generator to the microfluidic device in a single file with a reasonable expectation of success (Stumbo, abstract)(MPEP 2143)(I)(G).
The teachings of modified Leblanc would yield the second joint device (fluid transporter and the corresponding chip port) comprises a second joint portion (Stumbo, fluid transporter between junction 106 to 178), the second joint portion comprises a first joint (Fig. 6 of Stumbo, junction 106 to 74) and a second joint (Fig. 6 of Stumbo, outflow port 178), the second joint is connected to the second opening (after the modification, 212 of Stumbo is the tubing of Leblanc’s Fig. 9B, and outflow port 178 of Stumbo is the tubing opening is in the plastic chip port), the first joint is away from the second opening (Fig. 9B of Leblanc and Fig. 6 of Stumbo), a size of the first joint along a direction perpendicular to an extension direction of the flow path is smaller than a size of the second joint along the direction perpendicular to the extension direction of the flow path (Fig. 6 of Stumbo, the diameter of 74 is smaller than the diameter of 178).
Regarding claim 29, modified Leblanc teach The sample analysis system according to claim 28, wherein the second joint device (fluid transporter and the corresponding chip port) further comprises a second interface block (Stumbo Fig. 6, the portion of the fluidic transporter from 176 to 106 and a valve in the transporter as taught in para. 0038), the second interface block is connected to the first joint (junction 106 to 74) (Stumbo Fig. 6).
Leblanc teaches teach a plastic chip port is sleeved at the second joint (Fig. 9B), and thus fails to teach the second joint device comprises a second sealing member and the second sealing member is sleeved at the second joint (Fig. 9B).
However, Leblanc teaches the chip port forms a more reliable seal with a elastomer (para. 0010).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the plastic chip port in Fig. 9B taught by Leblanc to be made of elastomer in order to provide a more reliable seal with a reasonable expectation of success (Leblanc, para. 0010) (MPEP 2143)(I)(G).
The teachings of modified Leblanc would yield the second joint device comprises a second sealing member (chip port made of elastomer) and the second sealing member is sleeved at the second joint (Fig. 9B).
Regarding claim 30, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 29. Modified Leblanc further wherein the second interface block comprises a second liquid inlet channel (Stumbo, sample port 174, the port has a thickness thus it is interpreted as a channel), a second liquid outlet channel (Stumbo, the portion of 172 from 174 to 106), a second control valve group (Stumbo, para. 0038, transporter has a valve), and a second common channel (Stumbo, the portion of 172 from 180 to 174), and the second common channel is connected to the first joint (Fig. 6).
Regarding claim 31, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 30. wherein a hydraulic radius of each of the second liquid inlet channel (Stumbo, sample port 174) and the second common channel (Stumbo, the portion of 172 between 180 to 174) is greater than a hydraulic radius of the second liquid outlet channel (Stumbo, the portion of 172 between 180 to 174)(Figs. 6-7, the hydraulic radius of 172 where the droplets are in single file is smaller than radii of the other two channels).
Regarding claim 32, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 15.
Modified Leblanc teaches the top plate comprises pockets that forms inlet ports, for the gasket to be molded into (para. 0118, Configuration 3).
Leblanc teaches in Fig. 9B, configuration 1, an addition plastic chip port that sits in each of the of the top plate pockets.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the inlet pockets of the top plate to have with an additional plastic chip port because one of ordinary skill in the art would accordingly have recognized the additional plastic chip port in the inlet port would result in the predictable result of providing an inlet port (Fig. 9).
Modified fails to teach wherein the first joint device (pipette tip and the corresponding plastic chip port, Fig. 9B) comprises a first joint portion, a first interface block, and a first sealing member, an end of the first joint portion is connected to the first opening, and another end of the first joint portion is connected to the first interface block, the first sealing member is sleeved on the first joint portion.
However, Leblanc teaches the device is configured to detect a variety types of samples (para. 0096) and allow multiple samples to interact/coalescent (para. 0096). In addition, Leblanc further teaches the device is configured to accommodate different transport mechanism to introduce samples (para. 0124).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the middle inlet and pipette tip with an inlet (like the left inlet) that fit a tubing and a tubing to have another inlet for introducing droplets in order that two different droplet samples can interact or coalescent with a reasonable expectation of success (para. 0096) (MPEP 2143)(I)(G).
In addition, Leblanc teaches the chip port forms a reliable seal with a elastomer (para. 0010).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the plastic chip port in Fig. 9B taught by Leblanc to be made with elastomer in order to provide a more reliable seal with a reasonable expectation of success (Leblanc, para. 0010) (MPEP 2143)(I)(G).
The teachings of modified Leblanc yields the first joint device (tubing and corresponding chip port) comprises a first joint portion (tubing) and a sealing member (chip port made with elastomer), an end of the first joint portion is connected to the first opening (similar to the second opening and the corresponding tubing show in Fig. 9B, a portion of the tubing is directly connected to the first opening, and thus the entire tubing is connected to first opening through that portion) and the first sealing member is sleeved on the first joint portion (tubing is in the elastomer chip port)(Fig. 9B).
Leblanc further teaches droplets are formed before the sample fluid is introduced to the microfluidic device (para. 0082). Modified Leblanc further teaches a device that generates droplets is connected to a tubing such that the droplets can be introduced into the microfluidic device (see claim 15).
Modified Leblanc fails to teach wherein the first joint device comprises a first interface block, and another end of the first joint portion is connected to the first interface block.
However, Stumbo teaches a fluid transporter for transporting droplets from a reservoir to a another location in a single file configuration. Stumbo teaches the fluid transporter comprises a first joint portion (Stumbo Fig. 6, the portion of the fluid transport from 106 to 178), a first interface block (Stumbo Fig. 6, the part of the transporter from 176 to 106 and a valve in the transporter as taught in para. 0038), and an end of the first joint portion is connected to the first interface block (Stumbo Fig. 6).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the tubing of the Leblanc to with the fluid transporter taught by Stumbo in order to transport droplets from the droplet generator to the microfluidic device in a single file with a reasonable expectation of success (Stumbo, abstract)(MPEP 2143)(I)(G).
The teachings of modified Leblanc would yield wherein the first joint device (fluid transporter taught by Stumbo and the corresponding chip port) comprises a first joint portion (Fig. 6 of Stumbo, junction 106 to 178), a first interface block (Stumbo Fig. 6, the part of the transporter from 176 to 106 and a valve in the transporter as taught in para. 0038), and a first sealing member (chip port made with elastomer), an end of the first joint portion is connected to the first opening (similar to the second opening and the corresponding tubing show in Fig. 9B, a portion of the tubing is directly connected to the first opening, and thus the entire tubing is connected to second opening through that portion), and another end of the first joint portion is connected to the first interface block (Fig. 6 of Stumbo, junction 106 to 74) (Stumbo Fig. 6), the first sealing member is sleeved on the first joint portion (178 is in the elastomer chip port in modified Leblanc)(Fig. 9B).
Regarding claim 33, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 32. Modified Leblanc further wherein the first interface block comprises a first liquid inlet channel (Stumbo, 172), a first liquid outlet channel (Stumbo, 128a), a first control valve group (a valve in the transporter as taught in para. 0038 of Stumbo), and a first common channel (128b), and the first common channel is connected to the first joint portion (junction 106 to 178)(Fig. 6 of Stumbo).
Claims 18 is rejected under 35 U.S.C. 103 as being unpatentable over Leblanc et al. (US 20120244043) in view of Link (US 20120309002), and further in view of Jaffe et al. (US 20160123886 A1) as applied to claim 17, and further in view of Nakajima et al. (US 20190101742 A1).
Regarding claim 18, modified Leblanc teaches all of the elements of the current invention as stated above with respect to claim 17.
Modified Leblanc fails to explicitly teach wherein the focal length of the first lens assembly is 1 mm to 2 mm, the field diameter of the first lens assembly is 1 mm to 2 mm; the focal length of the second lens assembly is 1 mm to 2 mm, the field of view of the second lens assembly is 5 mm to 10 mm.
However, Nakajima teaches the focal points of the imaging section are changed in accordance with, e.g., the size of the material component to be analyzed” (para. 0058), and thus teaches focal length as well as the field of view and field diameter which are affected by focal length are result-effective variable. Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the focal length and field diameter of the first lens assembly to be 1 mm to 2 mm and 1 mm to 2 mm, respectively; and to modify the focal length and field of view of the second lens assembly to be 1 mm to 2 mm and 5 to 10 mm, respectively, because it would have been within the ambit of one of ordinary skill in the art to arrive at through routine experimentation.
Response to Arguments
Applicant’s arguments, see p. 10, filed 05/13/2026, with respect to objection to the Drawings have been fully considered and are persuasive. The objection has been withdrawn.
Applicant’s arguments, see p. 10, filed 05/13/2026, with respect to objection to the Specification have been fully considered and are not persuasive. The issue related to para. 0065 has not been addressed by the amendment. Therefore, the objection is maintained.
Applicant’s arguments, see p. 11, filed 05/13/2026, with respect to claim objections have been fully considered and are persuasive. The objection has been withdrawn.
Applicant’s arguments, see pp. 11-12, filed 05/13/2026, with respect to rejection under 35 U.S.C. 112(a) and under 35 U.S.C. 112(b) have been fully considered and are persuasive. The rejections have been withdrawn.
Arguments under 35 U.S.C. 103
Applicant’s argument, see top of p. 14 to top of p.15, filed 05/13/2026, has been fully considered and is not persuasive. The Applicant argues that the left and middle inlet ports are part of two inlet channels and thus fails to teach “the first opening and the second opening of a same flow path are adjacent to two opposite ends of the flow path…” as required by the amended claim 1.
The Examiner respectfully disagrees. Leblanc teaches the inlet channels are all connected to the main channel (para. 0096). Therefore, the left and middle inlet ports are fluidically connected, and thus there is a flow path between the two inlet ports, wherein each inlet port is at the opposite end of that flow path. Furthermore the flow path can include the main channel, for instance, the flow path can have one end at the left inlet that leads to the main channel, go down to the main channel for a distance, then change/reverse direction toward the middle inlet. Therefore, this argument is unpersuasive.
Applicant’s argument, see p.15, 2nd and 3rd paras, filed 05/13/2026, relating to the detection surface has been fully considered and is persuasive. Therefore, the rejection of claim 15 has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Leblanc et al. (US 20120244043) in view of Link (US 20120309002).
Applicant’s argument, see p. 15, 4th para to first para of p. 16, filed 05/13/2026, has been fully considered and is not persuasive. The Applicant argues that the port sizes of the inlets are not result-effective variables. The Applicant states that “the port size of Lablanc and the hydraulic radii of the first and the second openings of the present application are designed based on different factors.”
The examiner respectfully disagrees. As states on p.16 of OA of 02/25/2026, Leblanc. teaches “a port size is customized based on the type of transport mechanism, e.g. various pipette tips or various size or tubing (para. 0111 and Fig. 5),” and thus the port sizes of the inlets are result-effective variables. Furthermore, whether a particular variable in the reference is designed based on the same or different factors as the instant applicant, does not preclude the variable from being a result-effective variable. Therefore, this argument is unpersuasive.
Applicant’s argument, see p. 16, 2nd – 3rd para., filed 05/13/2026, has been fully considered and is not persuasive. The Applicant argues that the obviousness rejection based routine experimentation would not bring the size of Leblanc’s inlet port to the required range, which is a hydraulic radius of 0.02 mm to 0.2 mm. As support, the Applicant points out that a commonly used transport mechanism such as a pipette of 10 mL has and an outer diameter of about 2 mm, which is much different from the hydraulic radius of the second opening (0.02 mm to 0.2 mm) in amended claim 1.
The examiner respectfully disagrees. A pipette tip or a tubing is what get inserted into the inlet port and thus the outer diameter of a pipette tip or tubing (instead of an outer diameter pipette) is what should be considered. Motadel et al. (US 20110183433 A1) teach pipette tips of various sizes. Motadel discloses in para. 0067 that the outer diameter of the distal end of a pipette tip is around 0.02 inches which around 0.51 mm. According the para. 67 in the Specification of the instant application, the hydraulics radius of circular opening is radius 2/diameter that is radius/2. An outer diameter of 0.51 mm (or a radius of 0.255 mm), and would yield a hydraulic radius of 0.255/2 mm or ~0.13 mm, which is within the claimed range. Therefore, this argument is unpersuasive.
Applicant’s argument, see end of p. 16, filed 05/13/2026, relating to Jaffe, Nakajima and Stumbo do not cure the deficiencies of Leblanc has been considered and persuasive. Therefore, the rejection of under U.S.C. 103 of 02/25/2026 has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Leblanc et al. (US 20120244043) in view of Link (US 20120309002) in various combination of Jaffe, Nakajima, Stumbo and Fisher.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MAY CHIU whose telephone number is (571)272-1054. The examiner can normally be reached 9 am - 5 pm.
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/M.L.C./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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