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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 17 December 2025 has been entered.
Status of Claims
Applicant's amendments to the claims filed 17 December 2025 have been entered. Applicant's remarks filed 17 December 2025 are acknowledged.
Claims 7 and 11 are in status “Currently Amended.” Claims 8 – 10 are in status “Previously Presented.” Claims 1 – 6 and 12 are cancelled.
Response to Arguments
Applicant's arguments filed 17 December 2025 have been fully considered but they are not persuasive.
The examiner understands the instant invention claimed in amended claim 7 as follows; A sample tray is filled with a diluent/buffer. A biological sample is placed in an inlet of a microfluidic device, and flows through a microfluidic channel. The optical pathway of a flow cytometry device intersects this channel and detects particles of interest flowing through the channel. When a particle of interest is detected, a tray is moved underneath the outlet of the microfluidic channel to catch the sample, resulting a sample tray with a higher concentration of target particles.
From here, the sample tray is moved to a second position. In this second position, a capture device (such as a pipettor) uses an optics system to select a particular particle from the concentrated, pre-sorted particles, and move it to a third location.
Ultimately, the method of the instant application merely performs two sequential cell sorting steps using two different cell sorting devices known in the art; a flow cytometer which collects an output into a specific location (such as taught by Nassef et al or by Klas et al), and a pipetting-type capture device (such as taught by Handique et al). As discussed in more detail below, this combination would be obvious to anyone of ordinary skill in the art seeking to perform two sorting steps.
Regarding applicant’s remark that Nassef fails to disclose “that the sample reservoir 204 can be moved to the end of the interface plate, also nor teach the end of the interface plate is located above the sample reservoir and the waste,” this is not in scope with the claim language positively recited in independent claims 7 or 11. The sample reservoir reads on the sample inlet. Neither claims 7 nor 11 recite that the sample inlet moves. Nassef does teach that interface plate is located above the output container, and that droplets fall into the output container (see [0187]). The output container is read on the sample tray which collects the sample.
However, in the interest of furthering prosecution, a new grounds of rejection is put forward in view of Klas et al in view of Handique et al. Klas et al more explicitly teaches a microfluidic channel which drips into a sample collection container and in which the sample collection container is moveable.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7 – 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 7 recites the limitation "the waste liquid tank" in line 17. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the examiner interprets claim 7 to mean “the liquid tank” as recited in line 10.
Claims 8 – 10 are rejected as being indefinite due to their dependence on claim 7.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7 – 10 are rejected under 35 U.S.C. 103 as being unpatentable over Klas et al (US 20220163438 A1) in view of Handique et al (US 20190064168 A1, first cited in the office action dated 11 February 2025).
With regards to claim 7, Klas et al teaches;
The claimed “A method for detecting and collecting target biological particles” has been read on the taught ([0003], “…the present invention relates to systems and methods in a flow cytometer-based system for analyzing, handling, and processing fluids and components or particles in the sample.”);
The claimed “a liquid tank is provided for receiving the sample that is discharged from the second end of the microfluidic channel” has been read on the taught ([0197], “After processing, the fluid sample is collected in the automatic fluid collection system 14, or may automatically be diverted into a waste collection tube, reservoir, or container.”);
The claimed wherein the dilution apparatus further comprises “a sample tray assembly” has been read on the taught ([0025], “…the modular flow cytometry system may comprise […] a sample mixing and collection module…”; the sample mixing and collection module reads on a sample tray assembly.);
Klas et al does not explicitly teach a sample tray, but does teach a collection vessel in a sample tray assembly, as read on the taught ([0031], “…the sample mixing and collection module may comprise […] a set of collection tubes... One of the collection tubes can be positioned below the microfluidic chip such that the processed sample is collected in said collection tube.”);
Klas et al additionally teaches that the collection vessel may be filled prior to the addition of the sample, as read on the taught ([0354], “For example, the media may be buffered media that is in the tube prior to adding sample or added along with the sample.”);
“Wherein the second end of the microfluidic channel is distant to a liquid level of the diluter in the collection vessel” has been read on the taught ([0355], “The processed sample then drips, drops, or drains down, by operation of fluid pressure and/or gravity, through one or more channels or openings and into a sample collection tube.”; The sample dripping reads on the second end of the microfluidic channel being distant to a liquid level of the diluter.);
The claimed “providing a dilution apparatus” and “wherein the dilution apparatus comprises a microfluidic channel” have been read on the taught ([0026], “…the modular flow cytometry system for processing a sample may comprise […] a sample pathway module comprising a microfluidic module having at least one microfluidic channel…”);
The claimed wherein the dilution apparatus further comprises “a first optical detection module” has been read on the taught ([0025], “…the modular flow cytometry system may comprise […] an interrogation module…”; [0385], “… the interrogation module including a detector…”);
The claimed wherein “the microfluidic channel has a first end and a second end, wherein the first end of the microfluidic channel is connected to a sample reservoir” and “the sample in the sample reservoir flows into the microfluidic channel through the first end of the microfluidic channel and flows out through the second end of the microfluidic channel” have been read on the taught ([0239], “A channel 854 in the microfluidic module body 851 directs a sample fluid […] into a sample input 884, through a sample channel 885, into a common channel 886, through a detection region 887, and out through one or more outlets…”);
The claimed “providing a sample that contains the target biological particles by the sample reservoir” has been read on the taught ([0236], “In a flow cytometry system, when processing a biological fluid sample, the fluid 824 may be a semen sample, and the fluid reservoir 822 may be a sample tube.”);
The claimed “wherein the sample tray assembly comprises at least one sample tray for receiving a sample discharged through the second end of the microfluidic channel” has been read on the taught ([0236], “In a flow cytometry system, when processing a biological fluid sample, the fluid 824 may be a semen sample, and the fluid reservoir 822 may be a sample tube.”);
The claimed wherein “the first optical detection module provides a first optical pathway that penetrates through the microfluidic channel and is adapted to detect at least one of the target biological particles that passes through the microfluidic channel” has been read on the taught ([0334], “…one or more electromagnetic radiation emitters are directed at or to the chip using an optical pathway… The detection module collects or detects emissions from particles or components in the sample to identify one or more characteristics of the particles or components, such as an amount or type of DNA, and to provide feedback to the system and/or an operator.”);
The claimed “when the first optical detection module does not detect that the sample contains the target biological particles passing through the microfluidic channel, the sample is discharged from the second end of the microfluidic channel into the waste liquid tank” has been read on the taught ([0079], “Based on meeting a set of criteria or parameters, the processed sample is permitted to flow into a sample catch tube disposed on the sample mixing system or is diverted into a waste collection container.”; [0176], “Further examples of the automated features of the system include the auto-dump module which allows for the processed sample stream to be redirected to a waste collection…”);
“When the first optical detection module detects any of the target biological particles passing through the microfluidic channel, controlling the sample tray assembly to provide and move the collection reservoir to an opening of the second end of the microfluidic channel” has been read on the taught ([0335], “The actuator operates to move the diverter in or out of the path of a processed sample exiting the chip to either permit the sample to pass into a collection tube 5130 or to cause the sample to be diverted into a waste collection container or area.”; [0336], “The rotary base 5110 rotates in an arcuate path […] to rotate sample collection tubes on the base into a sample collection path.”);
“After a sample with the target biological particles passes through the microfluidic channel and the second end of the microfluidic channel, the target biological particles are loaded to the collection reservoir” has been read on the taught ([0335], “The actuator operates to move the diverter in or out of the path of a processed sample exiting the chip to either permit the sample to pass into a collection tube 5130…”).
While Klas et al does not explicitly teach “a diluter supplying device”, MPEP 2144.04(III) states that “… broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.” As providing a diluter supplying device to load the sample tray with media prior to loading the target biological particles accomplishes the same result as loading the sample tray with diluter by hand, the claim language is not sufficient to distinguish the instant invention over the prior art of Klas et al.
However, Klas et al does not explicitly disclose a sample tray; providing a selectively capturing apparatus, wherein the selectively capturing apparatus comprises a second optical detection module and a capturing device; the at least one sample tray is controlled to move the selectively capturing apparatus and locate at a position where the second optical detection module corresponds to the at least one sample tray; the second optical detection module is adapted to scan, identify, and locate an accurate position of each of the target biological particles on the at least one sample tray; the capturing device is connected to the second optical detection module by a signal; after the second optical detection module locates the accurate position of each of the target biological particles on at the at least one sample tray, controlling the capturing device to move to the accurate position of each of the target biological particle and capture the target biological particle; the capturing device is controlled to load the target biological particle that is captured to a collection plate.
In the analogous art of methods for detecting and collecting target biological particles, Handique et al teaches the following:
The claimed “a sample tray” has been read on the taught (Fig 3, substrate 110 including array of wells 120);
The claimed “providing a selectively capturing apparatus” has been read on the taught (Figure 1, system 100; Figure 21, method 200; After capturing the population of target cells, Block S210 can optionally include gathering information from […] and locating the captured cells in Block S216. Block S216 is preferably achieved using the imaging subsystem 194 described in Section 1, but can be achieved using any other method and/or component of the system 100.” System 100 reads on the selectively capturing apparatus.);
The claimed “wherein the selectively capturing apparatus comprises a second optical detection module” has been read on the taught (Figure 1, imaging subsystem 194; [0095], “The system 100 can additionally include an imaging subsystem 194 that functions to image the contents of the set of wells, and can further function to distinguish target objects […] captured in the set of wells from other cells or objects in the sample…”);
The claimed apparatus further comprising “a capturing device” has been read on the taught ([0101], "The system 100 can further include an extraction module (e.g., cell retrieval subsystem) that functions to extract at least one of a single cell and a cell cluster from a well 128 of the array.");
The claimed “the sample tray is controlled to move to the selectively capturing apparatus and locate at a position where the second optical detection module corresponds to the sample tray” has been read on the taught ([0114], “Block S210 recites receiving a population of target cells into an array of wells.” [0053] clarifies that receiving a population of target cells into an array of wells includes positioning the array of wells relative to system 100, “…the substrate 110 can be attached to a substrate platform 105 that functions to reversibly attach and align the substrate to a […] stage upon which assays are performed, wherein the stage can be used to physically adjust the position of the substrate within the system 100 to improve access of the array of wells to other elements of the system, such as the imaging subsystem 194.”);
The claimed “the second optical detection module is adapted to scan, identify, and locate an accurate position of each of the target biological particles on the sample tray” has been read on the taught ([0129], “After capturing the population of target cells, Block S210 can optionally include gathering information from the captured cells, including identifying, quantifying, and locating the captured cells in Block S216. Block S216 is preferably achieved using the imaging subsystem 194...”);
The claimed “the capturing device is connected to the second optical detection module by a signal” has been read on the taught ([0147], “…the extraction module can be used in operation with the imaging subsystem […] based on imaging feedback.” The imaging feedback reads on connection via a signal);
The claimed “after the second optical detection module locates the accurate position of each of the target biological particles on the sample tray, controlling the capturing device to move to the accurate position of each of the target biological particle and capture the target biological particle” has been read on the taught (Figure 18, block 230 recites “Re-distributing a subset of partially retained particles across the array of wells.”; [0129], “… Block S210 can optionally include […] locating the captured cells in Block S216… The information obtained in Block S216 can further be used to inform, modify, and/or adjust settings for subsequent or concurrent steps in method 200.” Block 230 is a subsequent step that can be modified with the location information; [0104] clarifies that the extraction module can move to the target particle, “The extraction module can be configured to facilitate advancement of a particle extractor to a well 128 containing a cell/particle cluster of interest, for instance, with an actuation subsystem.”; [0147] supports the step including the capturing device capturing the particle, “the extraction module can be used in operation with the imaging subsystem to retrieve one or more particles from a well...”);
The claimed “then, the capturing device is controlled to load the target biological particle that is captured to a collection plate” has been read on the taught (Figure 18, block 230, reads on loading a captured target biological particle to a new well among an array of wells. [0147] recites that the capturing device can be used for this purpose, “…the extraction module can be used in operation with the imaging subsystem to retrieve one or more particles from a well containing more than one particle and dispense them into another well containing no beads, based on imaging feedback.”; [0048] clarifies that the system can operate with multiple arrays of wells, “…the components of the system can be configured with any numerosity to accommodate any suitable number of arrays.”; Distribution one or more particles and dispensing them into another on a suitable number of arrays via the extraction module reads on the capturing device loading the target biological particle to a collection plate).
Handique et al additionally teaches that different reagents can be added at different times in a workflow in an automated fashion, as read on the taught ([0106], “According to one or more workflows, […] the correct types and volumes of materials (e.g., reagents/samples) are added to or removed from the sample processing cartridge at the correct times in an automated fashion.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of particle separation of Klas et al with the method of particle separation as taught by Handique et al, in order to use a microfluidic method with an increased probability that a given droplet contains a single cell of interest from a sample (Nassef et al, [0172], “The microfluidic nature of the technology allows for the volume of a single collection droplet to be decreased. Minimizing the volume of the collection droplets increases the probability that a given droplet contains exactly one isolated particle.”) for efficient subsequent cell capture (Handique et al, [0004], “The system and method described herein address these limitations by integrating functions such as single-cell capture […] in order to enable more advanced biochemical processes to be performed on individual […] thereby vastly improving capture efficiency for desired cells…”).
With regards to claim 8, the method of claim 7 is obvious over Klas et al in view of Handique et al.
Klas et al additionally teaches;
The claimed “wherein the first optical detection module comprises a first light source and a first optical detector” has been read on the taught ([0262], “The flow cytometry apparatus or microfluidic device may further comprise a laser configured to emit electromagnetic radiation along a beam path to the particle interrogation location and a detector configured to detect an emission from the particle.”);
The claimed “the first light source and the first optical detector are disposed at two planes that are not parallel to the microfluidic channel, respectively, so that the first optical pathway passes through the microfluidic channel” has been read on the taught ([0275], “With reference now to FIG. 25A, a block diagram of an opto-mechanical system 3400 for positioning a set of laser assemblies 3410 comprising a detection laser assembly 3430 […]on the opposite side of a detection assembly 3450... The opto-mechanical system 3400 is used to detect certain characteristics of particles […] passing through an action or interrogation area 3404 in a flow path 3402 of a flow cytometer system, such as in a channel of a microfluidic chip.”; Figure 25A shows that the light source 3430 and detection assembly 3450 are an opposite sides of microfluidic channel 3402.).
With regards to claim 9, the method of claim 7 is obvious over Klas et al in view of Handique et al.
The prior art of Klas et al in view of Handique et al does not explicitly teach the claimed distances between the second end of the microfluidic channel, bottom surface of a slot on the at least one sample tray, height of the diluter, or distance between the second end of the microfluidic channel and the liquid level of the diluter. However, according to MPEP 2144.04(IV)(A), changes in size or proportion do not render a claimed invention distinct from the prior art device provided that “…a device having the claimed relative dimensions would not perform differently than the prior art device.” See In Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984).
The specification of the instant application notes in [0024] that the only purpose of the recited dimensions is to avoid retaining the sample droplet on the end of the microfluidic channel, and to reduce the impact on biological particles when the droplet falls. Klas et al explicitly teaches that the channel drips into the collection vessel, as read on ([0355], “The processed sample then drips, drops, or drains down, by operation of fluid pressure and/or gravity, through one or more channels or openings and into a sample collection tube.”). Accordingly, the device as taught by Klas et al in view of Handique et al does not function differently than the claimed invention.
As such, the method of claim 9 is not distinct over Klas et al in view of Handique et al.
With regards to claim 10, the method of claim 7 is obvious over Klas et al in view of Handique et al.
Klas et al additionally teaches;
The claimed “wherein a mixing device makes the target biological particle be evenly distributed in the at least one sample tray” has been read on the taught ([0354], “The dispensing instrument can dispense a sample into one of the collection tubes 5130 as the rotary base moves in the arcuate path. In a preferred embodiment, the collection tube 5130 receiving the sample remains under a dispensing path of the dispensing instrument as said collection tube 5130 moves in the arcuate path, thereby mixing the sample in the collection tube 5130. […] The media is mixed or agitated to maintain buffering and control a degree of buffering.”).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Klas et al (US 20220163438 A1) in view of Handique et al (US 20190064168 A1, first cited in the office action dated 11 February 2025) and further in view of Vercruysse (US 20200018684 A1, first cited in the office action dated 11 February 2025).
With regards to claim 11, Klas et al teaches;
The claimed “A method for detecting and collecting target biological particles” has been read on the taught ([0003], “…the present invention relates to systems and methods in a flow cytometer-based system for analyzing, handling, and processing fluids and components or particles in the sample.”);
The claimed “providing a dilution apparatus” and “wherein the dilution apparatus comprises a microfluidic channel” have been read on the taught ([0026], “…the modular flow cytometry system for processing a sample may comprise […] a sample pathway module comprising a microfluidic module having at least one microfluidic channel…”);
The claimed wherein the dilution apparatus further comprises “a sample tray assembly” has been read on the taught ([0025], “…the modular flow cytometry system may comprise […] a sample mixing and collection module…”; the sample mixing and collection module reads on a sample tray assembly.);
Klas et al does not explicitly teach a sample tray, but does teach a collection vessel in a sample tray assembly, as read on the taught ([0031], “…the sample mixing and collection module may comprise […] a set of collection tubes... One of the collection tubes can be positioned below the microfluidic chip such that the processed sample is collected in said collection tube.”);
The claimed wherein the dilution apparatus further comprises “a first optical detection module” has been read on the taught ([0025], “…the modular flow cytometry system may comprise […] an interrogation module…”; [0385], “… the interrogation module including a detector…”);
The claimed wherein “the microfluidic channel has a first end and a second end, wherein the first end of the microfluidic channel is connected to a sample reservoir” and “the sample in the sample reservoir flows into the microfluidic channel through the first end of the microfluidic channel and flows out through the second end of the microfluidic channel” have been read on the taught ([0239], “A channel 854 in the microfluidic module body 851 directs a sample fluid […] into a sample input 884, through a sample channel 885, into a common channel 886, through a detection region 887, and out through one or more outlets…”);
The claimed “providing a sample that contains the target biological particles by the sample reservoir” has been read on the taught ([0236], “In a flow cytometry system, when processing a biological fluid sample, the fluid 824 may be a semen sample, and the fluid reservoir 822 may be a sample tube.”);
The claimed “a waste liquid tank is provided for receiving the sample that is discharged from the second end of the microfluidic channel” has been read on the taught ([0197], “After processing, the fluid sample is collected in the automatic fluid collection system 14, or may automatically be diverted into a waste collection tube, reservoir, or container.”);
The claimed wherein “the first optical detection module provides a first optical pathway that penetrates through the microfluidic channel and is adapted to detect at least one of the target biological particles that passes through the microfluidic channel” has been read on the taught ([0334], “…one or more electromagnetic radiation emitters are directed at or to the chip using an optical pathway… The detection module collects or detects emissions from particles or components in the sample to identify one or more characteristics of the particles or components, such as an amount or type of DNA, and to provide feedback to the system and/or an operator.”);
The claimed “when the first optical detection module does not detect that the sample contains the target biological particles passing through the microfluidic channel, the sample is discharged from the second end of the microfluidic channel into the waste liquid tank” has been read on the taught ([0079], “Based on meeting a set of criteria or parameters, the processed sample is permitted to flow into a sample catch tube disposed on the sample mixing system or is diverted into a waste collection container.”; [0176], “Further examples of the automated features of the system include the auto-dump module which allows for the processed sample stream to be redirected to a waste collection…”;
Regarding the limitation, “wherein the dilution apparatus comprises a diluter supplying device, the diluter supplying device adds a diluter into the at least one sample tray”;
Klas et al teaches that the collection vessel may be filled prior to the addition of the sample, as read on the taught ([0354], “For example, the media may be buffered media that is in the tube prior to adding sample or added along with the sample.”);
While Klas et al does not explicitly teach “a diluter supplying device”, MPEP 2144.04(III) states that “… broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.” As providing a diluter supplying device to load the sample tray with media prior to loading the target biological particles accomplishes the same result as loading the sample tray with diluter by hand, the claim language is not sufficient to distinguish the instant invention over the prior art of Klas et al.
“Wherein the second end of the microfluidic channel is distant to a liquid level of the diluter in the collection vessel” has been read on the taught ([0355], “The processed sample then drips, drops, or drains down, by operation of fluid pressure and/or gravity, through one or more channels or openings and into a sample collection tube.”; The sample dripping reads on the second end of the microfluidic channel being distant to a liquid level of the diluter.);
“When the first optical detection module detects any of the target biological particles passing through the microfluidic channel, controlling the sample tray assembly to provide and move the collection reservoir to an opening of the second end of the microfluidic channel” has been read on the taught ([0335], “The actuator operates to move the diverter in or out of the path of a processed sample exiting the chip to either permit the sample to pass into a collection tube 5130 or to cause the sample to be diverted into a waste collection container or area.”; [0336], “The rotary base 5110 rotates in an arcuate path […] to rotate sample collection tubes on the base into a sample collection path.”);
The claimed “after a sample with the target biological particles passes through the microfluidic channel and the second end of the microfluidic channel, the target biological particles are loaded to the sample tray and the sample droplet discharged through the second end of the microfluidic channel could smoothly drip into the diluter” has been read on the taught ([0355], “The sample is inserted into the flow cytometer, is processed by one or more systems or elements of the flow cytometer, and is expelled through one or more outlets at a terminal end of the flow cytometer… The processed sample then drips, drops, or drains down, by operation of fluid pressure and/or gravity, through one or more channels or openings and into a sample collection tube.”; See also [0562], which clarifies that the microfluidic chip is part of the flow cytometry system and forms a sample pathway with an inlet and an outlet.);
However, Klas et al does not explicitly disclose a sample tray; providing a selectively capturing apparatus, wherein the selectively capturing apparatus comprises a second optical detection module and a capturing device; the at least one sample tray is controlled to move the selectively capturing apparatus and locate at a position where the second optical detection module corresponds to the at least one sample tray; the second optical detection module is adapted to scan, identify, and locate an accurate position of each of the target biological particles on the at least one sample tray; the capturing device is connected to the second optical detection module by a signal; after the second optical detection module locates the accurate position of each of the target biological particles on at the at least one sample tray, controlling the capturing device to move to the accurate position of each of the target biological particle and capture the target biological particle; the capturing device is controlled to load the target biological particle that is captured to a collection plate.
In the analogous art of methods for detecting and collecting target biological particles, Handique et al teaches the following:
The claimed “a sample tray” has been read on the taught (Fig 3, substrate 110 including array of wells 120);
The claimed “providing a selectively capturing apparatus” has been read on the taught (Figure 1, system 100; Figure 21, method 200; After capturing the population of target cells, Block S210 can optionally include gathering information from […] and locating the captured cells in Block S216. Block S216 is preferably achieved using the imaging subsystem 194 described in Section 1, but can be achieved using any other method and/or component of the system 100.” System 100 reads on the selectively capturing apparatus.);
The claimed “wherein the selectively capturing apparatus comprises a second optical detection module” has been read on the taught (Figure 1, imaging subsystem 194; [0095], “The system 100 can additionally include an imaging subsystem 194 that functions to image the contents of the set of wells, and can further function to distinguish target objects […] captured in the set of wells from other cells or objects in the sample…”);
The claimed apparatus further comprising “a capturing device” has been read on the taught ([0101], "The system 100 can further include an extraction module (e.g., cell retrieval subsystem) that functions to extract at least one of a single cell and a cell cluster from a well 128 of the array.");
The claimed “the sample tray is controlled to move to the selectively capturing apparatus and locate at a position where the second optical detection module corresponds to the sample tray” has been read on the taught ([0114], “Block S210 recites receiving a population of target cells into an array of wells.” [0053] clarifies that receiving a population of target cells into an array of wells includes positioning the array of wells relative to system 100, “…the substrate 110 can be attached to a substrate platform 105 that functions to reversibly attach and align the substrate to a […] stage upon which assays are performed, wherein the stage can be used to physically adjust the position of the substrate within the system 100 to improve access of the array of wells to other elements of the system, such as the imaging subsystem 194.”);
The claimed “the second optical detection module is adapted to scan, identify, and locate an accurate position of each of the target biological particles on the sample tray” has been read on the taught ([0129], “After capturing the population of target cells, Block S210 can optionally include gathering information from the captured cells, including identifying, quantifying, and locating the captured cells in Block S216. Block S216 is preferably achieved using the imaging subsystem 194...”);
The claimed “the capturing device is connected to the second optical detection module by a signal” has been read on the taught ([0147], “…the extraction module can be used in operation with the imaging subsystem […] based on imaging feedback.” The imaging feedback reads on connection via a signal);
The claimed “after the second optical detection module locates the accurate position of each of the target biological particles on the sample tray, controlling the capturing device to move to the accurate position of each of the target biological particle and capture the target biological particle” has been read on the taught (Figure 18, block 230 recites “Re-distributing a subset of partially retained particles across the array of wells.”; [0129], “… Block S210 can optionally include […] locating the captured cells in Block S216… The information obtained in Block S216 can further be used to inform, modify, and/or adjust settings for subsequent or concurrent steps in method 200.” Block 230 is a subsequent step that can be modified with the location information; [0104] clarifies that the extraction module can move to the target particle, “The extraction module can be configured to facilitate advancement of a particle extractor to a well 128 containing a cell/particle cluster of interest, for instance, with an actuation subsystem.”; [0147] supports the step including the capturing device capturing the particle, “the extraction module can be used in operation with the imaging subsystem to retrieve one or more particles from a well...”);
The claimed “then, the capturing device is controlled to load the target biological particle that is captured to a collection plate” has been read on the taught (Figure 18, block 230, reads on loading a captured target biological particle to a new well among an array of wells. [0147] recites that the capturing device can be used for this purpose, “…the extraction module can be used in operation with the imaging subsystem to retrieve one or more particles from a well containing more than one particle and dispense them into another well containing no beads, based on imaging feedback.”; [0048] clarifies that the system can operate with multiple arrays of wells, “…the components of the system can be configured with any numerosity to accommodate any suitable number of arrays.”; Distribution one or more particles and dispensing them into another on a suitable number of arrays via the extraction module reads on the capturing device loading the target biological particle to a collection plate).
However, Klas et al in view of Handique et al does not explicitly disclose wherein the second optical detection module comprises a second light source, a lens assembly, a photomultiplier, and a charge-coupled device; the second light source generates a second optical pathway and a third optical pathway; the second optical pathway is started from the second light source and passes through the at least one sample tray and the lens assembly to the photomultiplier; the third optical pathway is started from the second light source and passes through the at least one sample tray and the lens assembly to the charge-coupled device; wherein when the target biological particles absorb excitation light emitted by the second light source, the target biological particles emit an emission light; the emission light enters the charge-coupled device along the third optical pathway; the charge-coupled device receives the emission light and captures an image of the target biological particles that emit the emission light, wherein the emission light enters the second photomultiplier along the second optical pathway, after the second photomultiplier receives the emission light, the second photomultiplier records the intensity of the emission light of the target biological particles.
In the analogous art of devices for testing analytes which include optical detection modules, Vercruysse teaches the following:
The claimed “a sample tray” has been read on the taught (Figure 1, substrate 105; [0059], “The present invention includes a substrate integrating the means for providing analytes to the region of interest and the means for focusing and/or collimating radiation emanating from the region of interest.”);
The claimed “an optical detection module” has been read on the taught (abstract, “It is an object of embodiments of the present invention to provide a fast, reliable and compact optical detector…”) comprising;
The claimed “a light source” has been read on the taught ([0093], “The sensing system can be coupled to at least one irradiation source or radiation carrier for generating an excitation radiation beam for exciting the particles to be characterized.”);
The claimed “a lens assembly” has been read on the taught (Figure 1, lens system 120; [0060]; “In some embodiments, a lens system comprising different thin lenses (e.g. Fresnel lenses with different designs, thin film lenses) may be attached to a surface of the substrate.”);
The claimed “a detector including a photomultiplier” has been read on the taught (Figure 1, detector system 130; [0081], “Such suitable detectors may comprise […] photomultipliers (e.g. Si-PMT), etc.”);
The claimed “a detector including a CCD” has been read on the taught (Figure 1, detector system 130; [0081], “Such suitable detectors may comprise CCD pixels...”);
The claimed “a detector array comprising multiple detectors” has been read on the taught (Figure 2, detection system 230; [0068], “The particle sensor may then comprise a plurality of detectors for detecting different wavelengths.”; [0070], “…the optical system can be optimized to transmit […] different wavelengths […] towards a different detector, for example by adapting each lens to each wavelength and aligning each lens to a different detector.”);
The claimed “a second optical pathway started from the second light source and passes through the sample tray and lens assembly to the photomultiplier” has been read on the taught (Figure 2, deflected radiation 111, lens system 120; [0078], “A portion of this radiation travels downwards the transparent substrate 105 and encounters the […] lens system 120 … These lenses deflect radiation 111, 112 to each of the different detectors 131, 132 in a detection system…”; Figure 1 shows individual detectors 131 and 132.);
The claimed “a third optical pathway started from the second light source and passes through the sample tray and the lens assembly to the charge-coupled device” has been read on the taught (Figure 2, deflected radiation 112, lens system 120; [0078], “A portion of this radiation travels downwards the transparent substrate 105 and encounters the […] lens system 120 … These lenses deflect radiation 111, 112 to each of the different detectors 131, 132 in a detection system…”; Figure 1 shows individual detector 131 and 132.);
Please see annotated figure 2 below showing separate optical pathways as taught by Vercruysse.
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The claimed “wherein when the target biological particles absorb the excitation light emitted by the second light source, the target biological particles emit an emission light” has been read on the taught (Figure 1, excitation beam 100, analyte 109, radiation signal 110; [0003], “…detecting the labelled particles by irradiating them with an excitation source and detecting the fluorescent emission.”)
The claimed “the emission light enters the charge-coupled device along the third optical pathway” has been read on the taught (See annotated figure 2 above for schematic of third optical pathway; [0078], “These lenses deflect radiation 111, 112 to each of the different detectors 131, 132 in a detection system…”);
The claimed “the charge-coupled device receives the emission light and captures an image of the target biological particles that emit the emission light” has been read on the taught ([0081], “…the present invention allows obtaining fluorescent images of cells with subcellular resolution, by combination of fluorescent detectors and an excitation radiation adapted to illuminate the particles crossing the ROI with a predetermined resolution (e.g. a thin light sheet with a known thickness) and image the fluorescence received by the detectors… Such suitable detectors may comprise CCD pixels…”)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the second optical detection module as taught by Nassef et al in view of Handique et al in view of Spence et al with the fluorescence detection system as taught by Vercruysse, in order to make use of multiple fluorescent biomarkers for analytes of interest while reducing strain in the sensing system (Vercruysse, [0021], “In some embodiments adapted for fluorescence analysis of analytes attached to fluorescence biomarkers, different biomarkers and combinations thereof may be separately detected by each detector of the system, reducing strain in the sensing system…”).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Nassef et al (US 20200096436 A1, first cited in the office action dated 11 February 2025) teaches a method for detecting and collecting biological particles including a dispensing nozzle which drips particles and a moveable collection assembly.
Wu et al (US 20200376488 A1) teaches a microfluidic device for sorting cells including an optical sensor.
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/ALISON CLAIRE GERHARD/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797