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 04/15/2026 has been entered. Claims 1-2, 4, 6-10 remain pending in the application. Applicant’s amendments to the claims have overcome each and every 112(b) rejections previously set forth in the Non-Final Office Action mailed 01/16/2026. New grounds of rejections necessitated by amendments are discussed below.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Kei et al. (US 20210382062 A1; cited in the IDS filed 11/06/2023) in view of Tovar et al. (US 20160129443 A1) and Kuramochi et al. (US 20160176191 A1).
Regarding claim 1, Kei teaches a biological particle analysis method (Fig. 2; paragraphs [0062]-[0074] teaches a method for analysis of cells), comprising:
a staining step implemented by fluorescence staining a liquid specimen having a plurality of biological particles through a fluorescence staining process (Fig. 2 and paragraph [0066], step S102 teaches fluorescently staining cells with a staining dispensing unit), so that at least one of the biological particles becomes a fluorescence color and is defined as at least one target biological particle (Fig. 2 and paragraph [0066], step S102 teaches fluorescently staining cells, which performs antibody staining, secondary antibody staining, nuclear staining, and the like on cells; paragraph [0068] teaches imaging of fluorescently stained cells, therefore at least one cell becomes a fluorescence color and interpreted as a target biological particle);
an analyzing step implemented by accommodating the liquid specimen being fluorescence stained into a well, and using a camera device to take a real-time image of the liquid specimen (Fig. 2 and paragraph [0069] teaches step S105 of using an image acquisition unit to acquire images, i.e. real-time image, of a well containing the cells fluorescently stained, i.e. accommodating the liquid specimen; paragraphs [0037]-[0038] teaches the image acquisition unit includes a camera for fluorescence observation);
a capturing step implemented wherein at least one target biological particle is captured by a biochip (paragraphs [0063] and [0066] teaches the cells are arranged in wells of a microplate, i.e. biochip);
a washing step implemented by removing the fluorescent color of the at least one target biological particle captured by the biochip through a washing process (Fig. 2 and paragraph [0071] teaches step S107 of using a washer unit to destain the cells fluorescently stained using washer solution); and
a characterization expressing step implemented by fluorescence staining the at least one target biological particle captured by the biochip for N number of times through the fluorescence staining process and the washing process (Fig. 2 and paragraphs [0073]-[0074] teaches step S109 of repeating fluorescent staining step S102 and destaining step S107), and using a recording device to obtain a plurality of fluorescence images respectively corresponding to N kinds of biological characterization expressions (Fig. 2 and paragraphs [0073]-[0074] teaches repeating iterations of fluorescent imaging step S105; paragraphs [0037]-[0038] teaches the image acquisition unit includes a camera for fluorescence observation; therefore, a recording device is used to obtain fluorescent images corresponding to N kinds of biological characterization expressions since multiple cycles or iterations of staining, imaging, and destaining is performed).
Kei fails to teach:
an analyzing step implemented by accommodating the liquid specimen being fluorescence stained into a pico-droplet generator, and using a camera device to take a real-time image of the liquid specimen in the pico-droplet generator;
wherein the pico-droplet generator includes a container, a hollow needle, and a top piezoelectric member disposed on the container, the container receives the liquid specimen, and the hollow needle is in fluid communication with the container by being connected to a bottom side of the container,
wherein an inner diameter of the container is within a range from 5 times to 30 times of an inner diameter of the hollow needle, and the top piezoelectric member is configured to vibrate the container for enabling the biological particles in the container to be arranged along a predetermined path of the hollow needle, and wherein the camera device corresponds in position to the hollow needle, and the camera device is configured to take real-time image of the liquid specimen in a free end of the hollow needle;
the capturing step implemented by using the pico-droplet generator to output a target pico-droplet having the at least one target biological particle onto a biochip according to the real-time image, wherein the at least one target biological particle in the target pico-droplet is captured by the biochip;
the washing step implemented by removing the fluorescent color of the at least one target biological particle in the target pico-droplet captured by the biochip through a washing process;
wherein N is a positive integer within a range from 2 to 50.
Kei teaches the number of iterations of the cycle of fluorescent staining, fluorescent imaging, and destaining based on a user input operation (paragraph [0064]). Kei teaches an embodiment where when the number of fluorescent colors used in fluorescent staining is four, for example, the predetermined number for repeating cycles of staining, imaging, and destaining, is four (paragraph [0079]). Kei teaches the processes of fluorescent staining, fluorescent imaging, and destaining of several types of proteins are repeated for all of the many types of proteins found in cells (paragraph [0024]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the characterization expressing step of Kei to incorporate the teachings of repeating multiple iterations or cycles of staining, fluorescent imaging, and destaining, such as four, of Kei (paragraphs [0064],[0079]) to provide: wherein N is a positive integer within a range from 2 to 50. Doing so would have a reasonable expectation of successfully improving imaging of many types of targets as taught by Kei (paragraph [0024]).
Modified Kei fails to teach:
an analyzing step implemented by accommodating the liquid specimen being fluorescence stained into a pico-droplet generator, and using a camera device to take a real-time image of the liquid specimen in the pico-droplet generator;
wherein the pico-droplet generator includes a container, a hollow needle, and a top piezoelectric member disposed on the container, the container receives the liquid specimen, and the hollow needle is in fluid communication with the container by being connected to a bottom side of the container, wherein an inner diameter of the container is within a range from 5 times to 30 times of an inner diameter of the hollow needle, and the top piezoelectric member is configured to vibrate the container for enabling the biological particles in the container to be arranged along a predetermined path of the hollow needle, and wherein the camera device corresponds in position to the hollow needle, and the camera device is configured to take real-time image of the liquid specimen in a free end of the hollow needle;
the capturing step implemented by using the pico-droplet generator to output a target pico-droplet having the at least one target biological particle onto a biochip according to the real-time image, wherein the at least one target biological particle in the target pico-droplet is captured by the biochip;
the washing step implemented by removing the fluorescent color of the at least one target biological particle in the target pico-droplet captured by the biochip through a washing process.
Tovar teaches a method and system for isolation of picoliter droplets, i.e. pico-droplet generator, from a continuous stream of carrier fluid in a microfluidic system (abstract; Figs. 1-2), wherein the pico-droplet generator (Figs. 1-2) comprises a hollow needle (capillary 18). Tovar teaches a method of that is surprisingly efficient to isolate individual microfluidic droplets on the picoliter scale for subsequent analysis and/or a scale up of the content of the droplet, wherein it is desirable to isolate cells in picoliter droplets using the method that possess a certain enzyme that is labelled with a fluorescent marker (paragraph [0101]). Tovar teaches an analyzing step implemented by accommodating the liquid specimen being fluorescence stained into a pico-droplet generator, and using a camera device to take a real-time image of the liquid specimen in the pico-droplet generator (paragraphs [0104]-[0105] teach methods that include fluorescent and/or nonfluorescent imaging of the picoliter droplet is captured and processed for sorting picoliter droplets; paragraph [0037] teaches optical imaging of the picoliter droplet by a camera). Tovar teaches a photodetector at a free end of a hollow needle (Fig. 1 shows photodetector 16 at a relative free end of capillary 18; Fig. 2 shows photodiode 34 at a relative free end of capillary 18). Tovar teaches using subsequent processing to analyze the image, picoliter droplets containing bacteria that depict a predefined deviation in their growth yield may be sorted to the detector and subsequently deposited into wells; thereby allowing for fast optical preselection of bacteria based upon a criteria and allows for high flexibility (paragraph [0104]). Tovar teaches by detecting a fluorescent image of the cells contained in the droplet, picoliter droplets containing cells presenting these membrane proteins may be easily distinguished and isolated for further processing (paragraph [0105]). Tovar teaches due to the capability of the method to sort and deposit selected picoliter droplets fast and efficient, the preferred method is particularly suited for a high-throughput clonal analysis of a population of cells (paragraph [0107]). Tovar teaches a target pico-droplet is captured by a collection vessel (Fig. 1; paragraph [0111]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of modified Kei to incorporate Tovar’s teachings of a method of isolating and sorting microfluidic droplets using a pico-droplet generator and fluorescent markers, by a photodetector at an end of a hollow needle, teachings of a camera to take images of the picoliter droplet, and allowing for depositing analyzed droplets into specific wells (paragraphs [0037],[0101],[0104]-[0105],[0107],[0111]; Figs. 1-2) to provide: an analyzing step implemented by accommodating the liquid specimen being fluorescence stained into a pico-droplet generator, and using a camera device to take a real-time image of the liquid specimen in the pico-droplet generator; wherein the pico-droplet generator includes a hollow needle, and wherein the camera device corresponds in position to the hollow needle, and the camera device is configured to take real-time image of the liquid specimen in a free end of the hollow needle; the capturing step implemented by using the pico-droplet generator to output a target pico-droplet having the at least one target biological particle onto a biochip according to the real-time image, wherein the at least one target biological particle in the target pico-droplet is captured by the biochip; the washing step implemented by removing the fluorescent color of the at least one target biological particle in the target pico-droplet captured by the biochip through a washing process. Doing so would have a reasonable expectation of successfully improving optical preselection and fluidic sorting of desired target particles into the biochip for high-throughput analysis of the target particles as taught by Tovar (paragraphs [0101],[0104],[0105],[0107]).
Modified Kei fails to teach: wherein the pico-droplet generator includes a container and a top piezoelectric member disposed on the container, the container receives the liquid specimen, and the hollow needle is in fluid communication with the container by being connected to a bottom side of the container, wherein an inner diameter of the container is within a range from 5 times to 30 times of an inner diameter of the hollow needle, and the top piezoelectric member is configured to vibrate the container for enabling the biological particles in the container to be arranged along a predetermined path of the hollow needle.
Kuramochi teaches a liquid droplet forming apparatus (abstract; Fig. 5A). Kuramochi teaches a conventional liquid droplet forming apparatus (Fig. 5A; paragraph [0071]) comprising a container (liquid chamber 610), a hollow nozzle (621), and a top piezoelectric member (piezoelectric element 630) disposed on the container (Fig. 5A), the container receives a liquid specimen (Fig. 5A shows liquid chamber 610 receiving liquid specimen 650 via flow passage 620), and the hollow nozzle is in fluid communication with the container by being connected to a bottom side of the container (Fig. 5A), wherein an inner diameter of the container is larger than an inner diameter of the hollow nozzle (Fig. 5A), and the top piezoelectric member is configured to vibrate the container for enabling biological particles in the container to be arranged along a predetermined path of the hollow nozzle (Fig. 5A and paragraph [0071] teaches the piezoelectric element provides vibration to the particles 650, thereby dispersing the particles in a path of the nozzle 621). Kuramochi teaches the piezoelectric element is vibrated as shown as solid arrows to give motion energy to the precipitating particles through dispersing liquid held in the liquid chamber, thereby dispersing the precipitating particles 650 that are precipitated and congregated around the nozzle or flow passage as shown as dotted arrows (Fig. 5A; paragraph [0071]). Kuramochi teaches vibration to disperse liquid of particles to suppress variance of particles in a formed droplet and to prevent clogging of the nozzle, therefore allowing for continuous and stable ejection of particles in droplets (paragraph [0080]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the pico-droplet generator of modified Kei to incorporate Kuramochi’s teachings of a conventional droplet generator including a container on top of a nozzle, and a piezoelectric member on the container (Fig. 5A; [0071],[0080]) to provide: wherein the pico-droplet generator includes a container and a top piezoelectric member disposed on the container, the container receives the liquid specimen, and the hollow needle is in fluid communication with the container by being connected to a bottom side of the container, and the top piezoelectric member is configured to vibrate the container for enabling the biological particles in the container to be arranged along a predetermined path of the hollow needle. Doing so would have a reasonable expectation of successfully improve delivery of the liquid specimen to the hollow nozzle while improving dispersion of the particles within the pico-droplet generator, therefore allowing for suppression of variance of the particles in the pico-droplet and preventing clogging of the hollow needle, thus improving continuous and stable generation of the pico-droplets (Kuramochi, paragraphs [0071],[0080]).
Modified Kei fails to teach: wherein an inner diameter of the container is within a range from 5 times to 30 times of an inner diameter of the hollow needle.
Kuramochi teaches an inner diameter of the container (Fig. 5A, liquid chamber 610) is larger than an inner diameter of the hollow nozzle (Fig. 5A, nozzle 621).
MPEP 2144.05 (II)(B) holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of droplet generators, the selection of optimal experimental conditions including structural geometry and dimensions, e.g. diameters, affects fluidic parameters volume of the container and size of a droplet generated by the hollow needle. Thus, the inner diameters of the container and the hollow needle are a result effective variables.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified an inner diameter of the container and an inner diameter of the hollow needle of modified Kei to incorporate the teachings of a diameter of a container that is larger than a hollow nozzle (Fig. 5A) to provide: wherein an inner diameter of the container is within a range from 5 times to 30 times of an inner diameter of the hollow needle through routine experimentation (MPEP 2144.05 (II)). I.e., it would have been obvious to design and fabricate the container and hollow needle to modify the result-effective variables, i.e. inner diameters, and arrive at the claimed dimensions through routine optimization of workable dimensions for the container and hollow needle to optimize volume of the container and the size of the resulting pico-droplets.
Claims 2, 4 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Kei in view of Tovar and Kuramochi as applied to claim 1 above, and further in view of Zweifel et al. (US 20020106308 A1).
Regarding claim 2, modified Kei fails to teach the biological particle analysis method according to claim 1, wherein the pico-droplet generator includes a bottom piezoelectric member disposed on an outer surface of the hollow needle, and wherein, in the capturing step, the bottom piezoelectric member of the pico-droplet generator is operated to squeeze the hollow needle, so that the liquid specimen flows outwardly and passes through a free end of the hollow needle to form the target pico-droplet.
Tovar teaches a method and system for isolation of picoliter droplets, i.e. pico-droplet generator, from a continuous stream of carrier fluid in a microfluidic system (abstract). Tovar teaches a method of that is surprisingly efficient to isolate individual microfluidic droplets on the picoliter scale for subsequent analysis and/or a scale up of the content of the droplet, wherein it is desirable to isolate cells in picoliter droplets using the method that possess a certain enzyme that is labelled with a fluorescent marker (paragraph [0101]). Tovar teaches a pico-droplet generator (Figs. 1-2) includes a hollow needle (capillary 18) and a bottom dispenser disposed on an outer surface of the hollow needle (Fig. 1 shows dispenser 20 on an outer surface of the capillary 18), and the hollow needle receives the liquid specimen therein (Fig. 1), and wherein, in the capturing step, the bottom dispenser of the pico-droplet generator is operated, so that the liquid specimen flows outwardly and passes through a free end of the hollow needle to form the target pico-droplet (Fig. 1 and paragraphs [0057],[0112]).
Zweifel teaches a method and apparatus for preventing damage to capillaries used to dispense microdrops (abstract). Zweifel teaches it is known for liquid dispensing systems that employ a capillary tube to dispense picoliter drops of liquid can include a piezoelectric transducer surrounding the capillary tube, which allows for compressing of the capillary to expel a drop of liquid (paragraph [0016]). Zweifel teaches a piezoelectric transducer surrounding a capillary to compress a capillary tube to expel a drop for each pulse (paragraphs [0023]-[0024]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the pico-droplet generator of modified Kei to incorporate Tovar’s teachings of dispensing microfluidic droplets on the picoliter scale (paragraphs [0057],[0101],[0112]) and Zweifel’s teachings of a capillary tube to dispense picoliter drops of liquid can include a piezoelectric transducer surrounding the capillary tube, which allows for compressing of the capillary to expel a drop of liquid (paragraphs [0016],[0023]-[0024]) to provide: the biological particle analysis method according to claim 1, wherein the pico-droplet generator includes a bottom piezoelectric member disposed on an outer surface of the hollow needle, and wherein, in the capturing step, the bottom piezoelectric member of the pico-droplet generator is operated to squeeze the hollow needle, so that the liquid specimen flows outwardly and passes through a free end of the hollow needle to form the target pico-droplet. Doing so would have a reasonable expectation of successfully allowing for and improving control of dispensing picoliter drops of liquid from the hollow needle.
Regarding claim 4, modified Kei fails to teach: the biological particle analysis method according to claim 2, wherein, in the capturing step, according to the real-time image, a controlling device electrically coupled to the bottom piezoelectric member and the camera device is configured to drive the bottom piezoelectric member when the at least one target biological particle is located in the free end.
Tovar teaches a method and system for isolation of picoliter droplets, i.e. pico-droplet generator, from a continuous stream of carrier fluid in a microfluidic system (abstract). Tovar teaches a method of that is surprisingly efficient to isolate individual microfluidic droplets on the picoliter scale for subsequent analysis and/or a scale up of the content of the droplet, wherein it is desirable to isolate cells in picoliter droplets using the method that possess a certain enzyme that is labelled with a fluorescent marker (paragraph [0101]). Tovar teaches using subsequent processing to analyze the image, picoliter droplets containing bacteria that depict a predefined deviation in their growth yield may be sorted to the detector and subsequently deposited into wells; thereby allowing for fast optical preselection of bacteria based upon a criteria and allows for high flexibility (paragraph [0104]). Tovar teaches by detecting a fluorescent image of the cells contained in the droplet, picoliter droplets containing cells presenting these membrane proteins may be easily distinguished and isolated for further processing (paragraph [0105]). Tovar teaches due to the capability of the method to sort and deposit selected picoliter droplets fast and efficient, the preferred method is particularly suited for a high-throughput clonal analysis of a population of cells (paragraph [0107]). Tovar teaches a target pico-droplet is captured by a collection vessel (Fig. 1; paragraph [0111]).
Zweifel teaches a method and apparatus for preventing damage to capillaries used to dispense microdrops (abstract). Zweifel teaches it is known for liquid dispensing systems that employ a capillary tube to dispense picoliter drops of liquid can include a piezoelectric transducer surrounding the capillary tube, which allows for compressing of the capillary to expel a drop of liquid (paragraph [0016]). Zweifel teaches a piezoelectric transducer surrounding a capillary to compress a capillary tube to expel a drop for each pulse (paragraphs [0023]-[0024]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the pico-droplet generator of modified Kei to incorporate Tovar’s teachings of dispensing microfluidic droplets on the picoliter scale based on fluorescent images (paragraphs [0057],[0101],[0104]-[0105],[0107],[0112]) and Zweifel’s teachings of a capillary tube to dispense picoliter drops of liquid can include a piezoelectric transducer surrounding the capillary tube, which allows for compressing of the capillary to expel a drop of liquid (paragraphs [0016],[0023]-[0024]) to provide: the biological particle analysis method according to claim 2, wherein, in the capturing step, according to the real-time image, a controlling device electrically coupled to the bottom piezoelectric member and the camera device is configured to drive the bottom piezoelectric member when the at least one target biological particle is located in the free end. Doing so would have a reasonable expectation of successfully allowing for and improving control of dispensing picoliter drops of liquid from the hollow needle.
Regarding claim 6, Kei further teaches the biological particle analysis method according to claim 2, wherein, in the staining step (Fig. 2 and paragraph [0066], step S102 teaches fluorescently staining cells with a staining dispensing unit), the liquid specimen being fluorescence stained is received in a specimen container disposed on a carrying platform (Fig. 1 and paragraph [0066] teaches staining the cells S housed in housing unit 10, i.e. specimen container, disposed on a drive unit 50, i.e. carrying platform).
Modified Kei fails to teach: in the analyzing step, the pico-droplet generator is movable relative to the carrying platform and is capable of sucking the liquid specimen from the specimen container through the free end.
Kei teaches various dispensers movable relative to the carrying platform (Fig. 1, elements 20 and 40). Kei teaches a staining dispenser unit suctions a reagent from a reagent rack to dispense to cells housed in wells of a microplate (paragraph [0036]).
Zweifel teaches in a typical operation, the tip of a capillary is moved into contact with liquid in a container, and the liquid is aspirated, after which the capillary is moved to another location where the liquid is dispensed in one or more droplets as desired (paragraphs [0002],[0017],[0018]). Zweifel teaches a capillary is mounted on a movable support and moved to a location, such as a well of a microplate to aspirate a liquid, and then moved to a second location which microdrops of liquid are dispensed (paragraph [0018]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the analyzing step of modified Kei to incorporate the teachings of a tip of a capillary that is moved to aspirate liquid to dispense at a different location of Zweifel (paragraphs [0002],[0017]-[0018]) to provide: in the analyzing step, the pico-droplet generator is movable relative to the carrying platform and is capable of sucking the liquid specimen from the specimen container through the free end. Doing so would have a reasonable expectation of successfully improving versatility of the method by allowing desired liquid specimens to be aspirated and dispensed at desired locations.
Regarding claim 7, Kei further teaches the biological particle analysis method according to claim 6, wherein the biochip (Fig. 1, microplate 10) disposed on the carrying platform (Fig. 1 shows microplate 10 on drive unit 50). Modified Kei fails to teach: an abandoned liquid container disposed on the carrying platform and the pico-droplet generator is moveable relative to the carrying platform so as to output the target pico-droplet onto the biochip and output an abandoned pico-droplet not having the target biological particle into the abandoned liquid container.
Tovar teaches one of the wells of a collector serves as a waste well, wherein for the time during which no passage of a picoliter droplet is detected the outlet of the detection channel is aligned with said waste well which takes up the outflowing carrier fluid (paragraph [0062]). Tovar teaches picoliter droplets that do not meet the selection criteria are guided towards the waste reservoir (paragraph [0035]).
Zweifel teaches in a typical operation, the tip of a capillary is moved into contact with liquid in a container, and the liquid is aspirated, after which the capillary is moved to another location where the liquid is dispensed in one or more droplets as desired (paragraphs [0002],[0017],[0018]). Zweifel teaches a capillary is mounted on a movable support and moved to a location, such as a well of a microplate to aspirate a liquid, and then moved to a second location which microdrops of liquid are dispensed (paragraph [0018]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of modified Kei to incorporate the teachings of guiding droplets that do not meet criteria to a waste reservoir of Tovar (paragraphs [0035],[0062]) and the teachings of moving desired liquids to desired locations of Zweifel (paragraphs [0002],[0017]-[0018]) to provide: an abandoned liquid container disposed on the carrying platform and the pico-droplet generator is moveable relative to the carrying platform so as to output the target pico-droplet onto the biochip and output an abandoned pico-droplet not having the target biological particle into the abandoned liquid container. Doing so would have a reasonable expectation of successfully allowing for dispensing of droplets that do not meet a criteria to an abandoned liquid container, therefore improving processing and sorting of droplets.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Kei in view of Tovar in view of Kuramochi as applied to claim 1 above, and further in view of Huang et al. (US 20210293778 A1; cited in the IDS filed 11/06/2023).
Regarding claim 8, while Kei teaches comprehensive information enables comprehensive cell profiling of pathological sections for understanding and explaining the origin of individual diseases (paragraph [0025]), modified Kei fails to teach the biological particle analysis method according to claim 1, wherein the biochip includes a bottom layer, a plurality of capturing arms connected to the bottom layer and spaced apart from each other, and a surface modification layer that is formed on ends of the capturing arms, and wherein, in the capturing step, the biochip is configured to capture the at least one target biological particle through the capturing arms and the surface modification layer.
Huang teaches a catcher, a capture device, and a method for capturing at least one target biological particle (abstract; paragraph [0001]). Huang teaches a biochip (Figs. 1, 6, 7, 12, 13) includes a bottom layer (10), a plurality of capturing arms (20) connected to the bottom layer and spaced apart from each other (Fig. 1), and a surface modification layer that is formed on ends of the capturing arms (paragraph [0060] teaches the protruding structures 20 is modified with a molecular cluster that is configured to couple with a target biological particle), and wherein, in a capturing step, the biochip is configured to capture the at least one target biological particle through the capturing arms and the surface modification layer (Fig. 12 and paragraph [0065] teaches a target biological particle is trapped by at least two capture arms; paragraph [0060] teaches the protruding structures 20 is modified with a molecular cluster that is configured to couple with a target biological particle). Huang teaches how to increase the capture rate of rare cells and to effectively obtain a single intact rare cell through improvement of a structural design for overcoming the above issues has become one of the important topics that need to be solved in this field (paragraph [0006]), wherein the captured device and method effectively improve the issues associated with conventional catchers (paragraph [0007]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biochip of modified Kei to incorporate the teachings of capturing arms modified with a molecular cluster to couple to a target biological particle of Huang (paragraphs [0065],[0060]; Figs. 1, 6, 7, 12, 13) to provide: the biological particle analysis method according to claim 1, wherein the biochip includes a bottom layer, a plurality of capturing arms connected to the bottom layer and spaced apart from each other, and a surface modification layer that is formed on ends of the capturing arms, and wherein, in the capturing step, the biochip is configured to capture the at least one target biological particle through the capturing arms and the surface modification layer. Doing so would have a reasonable expectation of successfully improving capturing and analysis of target biological particles as taught by Huang (paragraphs [0006]-[0007]).
Regarding claim 10, modified Kei fails to teach the biological particle analysis method according to claim 8, wherein, in the capturing step, at least two of the capturing arms of the biochip are elastically swingable with respect to the bottom layer and are capable of clamping the at least one target biological particle.
Huang teaches a catcher, a capture device, and a method for capturing at least one target biological particle (abstract; paragraph [0001]). Huang teaches a biochip (Figs. 1, 6, 7, 12, 13) includes a bottom layer (10), a plurality of capturing arms (20) connected to the bottom layer and spaced apart from each other (Fig. 1), and a surface modification layer that is formed on ends of the capturing arms (paragraph [0060] teaches the protruding structures 20 is modified with a molecular cluster that is configured to couple with a target biological particle), and wherein, in a capturing step, the biochip is configured to capture the at least one target biological particle through the capturing arms and the surface modification layer (Fig. 12 and paragraph [0065] teaches a target biological particle is trapped by at least two capture arms; paragraph [0060] teaches the protruding structures 20 is modified with a molecular cluster that is configured to couple with a target biological particle). Huang teaches in the capturing step, at least two of the capturing arms of the biochip are elastically swingable with respect to the bottom layer and are capable of clamping the at least one target biological particle (Figs. 12-13; paragraph [0063], [0065]-[0066]; paragraph [0008] teaches the free end portion of any one of the two of the capture aims is attached with and carries the target biological particle so as to bend the corresponding supporting segment to have an elastic force, and a part of the target biological particle is trapped by the supporting segments of the two of the capture arms and is held by the elastic force). Huang teaches how to increase the capture rate of rare cells and to effectively obtain a single intact rare cell through improvement of a structural design for overcoming the above issues has become one of the important topics that need to be solved in this field (paragraph [0006]), wherein the captured device and method effectively improve the issues associated with conventional catchers (paragraph [0007]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biochip of modified Kei to incorporate the teachings of elastic capturing arms to hold and couple to a target biological particle of Huang (paragraphs [0008],[0065],[0060]; Figs. 1, 6, 7, 12, 13) to provide: the biological particle analysis method according to claim 8, wherein, in the capturing step, at least two of the capturing arms of the biochip are elastically swingable with respect to the bottom layer and are capable of clamping the at least one target biological particle.. Doing so would have a reasonable expectation of successfully improving capturing and analysis of target biological particles as taught by Huang (paragraphs [0006]-[0007]).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Kei in view of Tovar, Kuramochi, and Huang as applied to claim 8 above, and further in view of Hong et al. (US 20170168063 A1).
Regarding claim 9, modified Kei fails to teach the biological particle analysis method according to claim 8, wherein the surface modification layer is an arginylglycylaspartic acid (RGD) peptide layer.
Huang teaches each of the protruding structures 20 can be modified with a molecular cluster (e.g., antibodies, receptors, or specific markers) that is configured to only be coupled with the target biological particle, but the present disclosure is not limited thereto (paragraphs [0049], [0060]).
Hong teaches a method of capturing a CTC and CSC from a sample including a flow based multichannel device having a cell capture surface and a flow modification surface (abstract). Hong teaches a capturing agent is an RGD peptide, a cRGD peptide, RGD mimetics, peptides or proteins containing the RGD sequence, structural or functional equivalents thereof, or combinations thereof (paragraph [0080]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the surface modification layer of modified Kei to incorporate the teachings of a molecular cluster can be receptors or specific markers of Huang (paragraphs [0049],[0060]) and the teachings of a cel capture surface and modification surface, wherein a capturing agent includes a RGD peptide of Hong (abstract; paragraph [0080]) to provide: the biological particle analysis method according to claim 8, wherein the surface modification layer is an arginylglycylaspartic acid (RGD) peptide layer. Doing so would have a reasonable expectation of successfully improving specific capturing of desired cells.
Response to Arguments
Applicant’s arguments, see pages 6-9, filed 04/15/2026, with respect to the rejection(s) of claims 1-10 under 35 U.S.C. 103, specifically regarding amended claim 1, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kei et al. (US 20210382062 A1; cited in the IDS filed 11/06/2023) in view of Tovar et al. (US 20160129443 A1) and Kuramochi et al. (US 20160176191 A1).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kanda (US 20070195310 A1) teaches a system for imaging the flow and a droplet (abstract; Fig. 4), wherein droplets are generated (Fig. 4). Kanda teaches the system includes a droplet generator (Fig. 4) comprising a container (Fig. 4, laminar-flow generating vessel 40 and element 70), a hollow needle (Fig. 4, interpreted as the hollow portion 71 that acts as a needle for fluid), and a top piezoelectric member disposed on the container (Fig. 4 and paragraph [0080] teaches an oscillation generator 89 provided on cylinder 42 of vessel 40; paragraph [0077] teaches oscillation generator 89 incorporates a piezoelectric actuator), the container receives a liquid specimen (Fig. 4 and paragraph [0080] teaches vessel 40 is capable of receiving a fluid, therefore is capable of receiving a liquid specimen), and the hollow needle (Fig. 4, hollow portion 71) is in fluid communication with the container (Fig. 4, laminar-flow generating vessel 40 and element 70) by being connected to a bottom side of the container (Fig. 4), wherein an inner diameter of the container is larger than of an inner diameter of the hollow needle (Fig. 4), and the top piezoelectric member (Fig. 4, oscillation generator 89) is configured to vibrate the container for enabling biological particles in the container to be arranged along a predetermined path of the hollow needle (Fig. 4). Kanda teaches the piezoelectric member (Fig. 4, oscillation generator 89) provides oscillation to properly split laminar flow of a fluid into droplets (paragraph [0082]).
Kagami (US 20040227790 A1) teaches a droplet generator (abstract; Fig. 1) comprising a piezoelectric member (13) on a container (channel 49). Kagami teaches vibration of the piezoelectric element is transmitted to vibrate the ink guide, thereby shaking the ink in the narrow channel and smoothly guiding the ink to the tip of the ink guide; and the vibration prevents adhesion of particles on the inner walls of the channels, removes particles that have adhered, and prevents failure to eject ink (paragraph [0083]).
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 HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
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