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 .
This action is responsive to the amendment of 3/6/2026.
Response to Arguments
Specification
The objection to the specification is overcome by amendment.
35 U.S.C. § 112
The claim elements interpreted under 35 U.S.C. § 112(f) have been removed by amendment with the exceptions of the detection units in claims 18 and 19. Removed claim elements are no longer interpreted.
The rejections under 35 U.S.C. § 112 are overcome by amendment.
35 U.S.C. § 103
Applicant’s first argument is that the previous action relies on a belief that inertial separation based on a spiral flow channel is an undesired function in Howell and that it would not have been obvious to remove the spiral and the inertial separation that results therefrom, however, this argument is not persuasive. First, the previous action does not rely on Howell finding inertial separation undesirable, but that a person of ordinary skill in the art might find inertial particle separation undesirable later. That other person of ordinary skill would then find it obvious to remove the feature that causes the undesired inertial separation, as described in MPEP 2144.04 II A. In light of MPEP 2144.04 II B, a secondary reference is relied on in this action to teach particle sorting that is based on bioparticle information (as now claimed) rather than based on inertia in a spiraled flow channel.
Applicant’s second argument is that using a straight flow channel instead of a spiral-shaped flow channel would render Howell unsatisfactory for its intended purpose, however, this argument is not persuasive. The intended purpose of Howell appears to be to explore “for the first time the potential of an event-based camera for particle and fluid behaviour characterisation in a microfluidic system” (abstract of Howell) and to demonstrate certain advantages to that approach, such as its compatibility with “a standard fluorescence microscope” (abstract of Howell). Howell does not appear to express an additional motivation to control which of the four outlets in FIG. 2 C the polystyrene spheres exit the system through. (In contrast, the background section of Ortyn describes several motivations to sort cells, but based on imaging the cells rather than using inertial separation.) While the portion Applicant quotes from the conclusions section of Howell suggests that using a straight channel might provide less of a challenge against which to demonstrate the advantages of event-based detection, that does not show that a straight channel would fail to demonstrate all the advantages of such an imaging system.
Since the arguments regarding claim 1 are not persuasive, the other independent claims are not made allowable for similar reasons, and the dependent claims are not automatically allowable.
Claim Objections
Claim 20 is objected to because of the following informalities: in the last line, “sorting” would fit better grammatically into the list of method steps that “sort”. 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:
the detection unit in claims 18 and 19, interpreted as corresponding to the detection unit described in paragraph 16 (an event-based vision sensor).
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.
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.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Howell (Non-Patent Literature “High-speed particle detection and tracking in microfluidic devices using event-based sensing”) in view of Ortyn (US Patent 6608682), further in view of Kaduchak (US patent publication 20180284009).
Regarding claim 1, Howell teaches a biological sample analysis system including:
at least one processor (section Imaging setup, third paragraph, running the MATLAB imaging pipeline) configured to:
irradiate a particle in a sample with light (FIG. 2 A, illumination, depicted as a green light bulb.);
detect, using a plurality of pixels of the sample analysis system (FIG. 2 A, Event-based camera), as an event, a luminance change of light emitted from the particle by irradiation with the light (FIG. 1 demonstrates the function of an event-based camera); and
generate particle information regarding the particle on a basis of the event detected by each of the pixels (section Imaging setup, third paragraph, running the MATLAB imaging pipeline); and
the plurality of pixels (FIG. 2 B, in the chip visible in the event-based camera); and
a predetermined flow channel (FIG. 2 C) wherein the predetermined flow channel is with a width of 1 mm or less (section Results, first paragraph, specifies a channel with widths of 360 µm and 60 µm along its two cross-sectional axes. Also see FIG. 3, which has a 200 µm scale bar. Comparing the length of the scale bar to the width of the channel even at the right-hand edge of the region of interest, the channel is only about half a mm wide).
While Howell does not explicitly describe the samples used as biological samples, nor the micrometer-scale polystyrene beads therein as bioparticles, Howell does explicitly state that their results “confirm that event-based cameras can be used to track individual particle behaviours in the size range of commonly used biological cells” (section Particle tracking and velocity mapping, fourth paragraph). Further, a claim for an apparatus generally does not distinguish patentably over the prior art due to recitations of the material or article worked upon by the apparatus. See MPEP 2115.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the event-based imaging flow cytometer of Howell with bioparticles, such as cells, in the manner that Howell contemplated.
While the flow channel disclosed by Howell is spiraled rather than straight, Howell does contemplate the use of sensor systems like the one Howell used with other channel designs (COL. 3, sentences 1-2), and the main purpose of Howell appears to be developing event-based imaging as a means to study microfluidics, describing the experiments presented as a “proof-of-principle” (abstract, sentence 6), rather than in inertially separating polystyrene beads with a spiral-shaped flow channel.
In the same field of endeavor of imaging and analyzing small moving objects, such as cells, Ortyn does teach a straight flow cell (FIG. 25, flow cell 306). By not including the spiral like that of Howell, Ortyn avoids the inertial separation of the particles across the fluid stream, allowing the whole width of the flow channel to be used for all sizes of particles. Note that it is generally considered obvious, when a particular function is not desired, to remove both an element (such as the curvature of a flow channel) and its undesired function (such as inertial particle separation). See MPEP 2144.04 II A.
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 event-based imaging flow cytometer of Howell without straight the spiral of the flow cell, following the example of Ortyn, to avoid inertial particle separation if one does not consider inertial particle separation to be a desired function, for example, to more efficiently use the entire width of the flow cell for imaging of particles of all sizes. Note that Ortyn also describes the use of cells, a type of bioparticle, in the sample (abstract).
While Howell does discuss sorting of particles, it is in the context of using a spiral-shaped or otherwise curved flow channel to perform inertial separation of the particles, which is different from using bioparticle information generated by a processor to perform sorting in a straight channel as claimed, so Howell does not teach a claimed way to sort the bioparticle on the basis of the generated bioparticle information. Likewise, Ortyn provides a motivation to sort cells (a type of bioparticle) as background to their invention, but does not teach a particular way of doing the sorting itself (even if the imaging techniques of Ortyn would be useful as part of a cell sorting device).
In the same field of endeavor of imaging flow cytometry, Kaduchak teaches a device to sort the bioparticle on the basis of the generated bioparticle information (FIG. 7, sorting module 790, positioned downstream of the image detector 774 and described in paragraph 82). By including a sorting module, Kaduchak is able to separate the particles based on information gathered about them, such as cellular functions (paragraph 82).
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 event-based imaging flow cytometer of Howell, as modified by Ortyn, to sort the particles after they are imaged in the manner of Kaduchak, to gain the predictable benefit of being able to perform high-speed sorting of cells or other bioparticles as motivated by Ortyn.
Regarding claim 2, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 1 (as described above).
Howell further teaches that the bioparticle moves in a first direction (FIG. 3, generally parallel to the x axis),
the plurality of pixels include two or more first pixels arranged adjacent to or separated from each other in the first direction (FIG. 3, multiple pixels exist along the x direction),
the at least one processor is further configured to output event data including information of time at which an event has been detected in each of the pixels (section titled Event-data collection and pre-processing, first paragraph), and
the at least one processor is further configured to align the pieces of information of time of a series of event data for each of the first pixels by detecting the luminance change of light emitted from the bioparticle by each of the first pixels (FIG. 7 shows data for several specific particles aligned across time as they move through the pixels), and generate the bioparticle information by processing the series of event data from each of the first pixels with the pieces of information of time aligned (FIG. 7 shows some of that information).
Regarding claim 3, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 2 (as described above).
Howell further teaches that the event data further includes at least one of position information of a pixel that has detected the event (FIG. 3. Note that the events are plotted based on their position) and polarity information of the event detected in the pixel (FIG. 1).
Regarding claim 4, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 2 (as described above).
Howell further teaches that the at least one processor is further configured to align the pieces of information of time of the series of event data for each of the first pixels on a basis of a relative speed of the bioparticle (FIG. 8 B aligns information based on speed to produce the probability density function) and an interval between the first pixels in the first direction (section titled Imaging setup, first paragraph. Also see scale bars in FIG. 3.).
Regarding claim 5, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 4 (as described above).
Howell further teaches that the at least one processor is further configured to measure the relative speed of the bioparticle using at least one of an optical method and an electromagnetic method (used to determine average fluid velocity in FIG. 5 and individual particle velocity in FIG. 7. The caption of FIG. 5 notes that the it is a distribution of particles detected in a video recorded with an event-based camera. Recording a video is an optical technique. Note that optical techniques are inherently electromagnetic, as optical signals (i.e., light) are a form of electromagnetic radiation.).
Regarding claim 6, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 2 (as described above).
Howell further teaches that the at least one processor is further configured to align the pieces of information of time of the series of event data for each of the first pixels on a basis of a difference in time at which each of the first pixels has detected the luminance change of light emitted from the bioparticle (FIG. 4).
Regarding claim 7, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 6 (as described above).
Howell further teaches that the at least one processor is further configured to align the pieces of information of time of the series of event data for each of the first pixels on a basis of a difference in time at which each of the first pixels has detected the luminance change of light emitted from the bioparticle in two or more pixel columns parallel to the first direction (note in FIG. 4 C that each of the three particles is shown as multiple pixels tall).
Regarding claim 8, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 2 (as described above).
Howell further teaches that the biological sample containing the bioparticle is delivered to the predetermined flow channel (FIG. 2 C), and
the at least one processor is further configured to align the pieces of information of time of the series of event data for each of the first pixels on a basis of a control value of a liquid delivery system that delivers the biological sample to the predetermined flow channel (section Microfluidic setup, first paragraph, describes how experiments were performed for varying flow rates with their corresponding velocities and Reynolds numbers. FIG. 6 shows data aligned based on those values.) .
Regarding claim 9, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 2 (as described above).
Howell further teaches that the at least one processor is further configured to generate the bioparticle information on a basis of a result of adding or dividing the series of event data for each of the first pixels in which the pieces of information of time are aligned on a time axis (FIG. 4 shows a process of dividing the relatively continuous time of the asynchronous event data into discrete frames.).
Regarding claim 10, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 9 (as described above).
Howell further teaches that the at least one processor is further configured to reconstruct the luminance change of light emitted from the bioparticle on a basis of the result of adding or dividing the series of event data for each of the first pixels in which the pieces of information of time are aligned on a time axis, and generates the bioparticle information on a basis of the reconstructed luminance change (section Event-data collection and pre-processing, second paragraph, describes doing analysis after the process of dividing the relatively continuous time of the asynchronous event data into discrete frames.).
Regarding claim 11, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 10 (as described above).
Howell further teaches that the at least one processor is further configured to reconstruct the luminance change of light emitted from the bioparticle for each of the first pixels for each of two or more pixel columns parallel to the first direction, and generate the bioparticle information on a basis of the luminance change for each of the first pixels in each of the two or more reconstructed pixel columns (FIG. 3. Note that the data comprises multiple rows and multiple columns of pixels, and that each of the particles is multiple pixels across.).
Regarding claim 12, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 1 (as described above).
Howell further teaches that the at least one processor is further configured to generate the bioparticle information using machine learning (section Particle tracking and velocity mapping, determining the particle tracks includes a training step, which is used to track which particle is which from one frame to the next and thereby determine the particle information) from a series of event data for each of the pixels by detecting the luminance change of light emitted from the bioparticle by each of the pixels (FIG. 1).
Regarding claim 13, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 1 (as described above).
Howell further teaches that the bioparticle information includes at least one of image data of the bioparticle reconstructed on a basis of the detected event (FIG. 3 and elsewhere), a feature amount of the bioparticle extracted from at least one of the detected event and the image data, and attribute information of the bioparticle generated from at least one of the event, the image data, and the feature amount (FIG. 6 B shows distance to inner wall, an attribute of a particle at a given time, based on reconstructed image data).
Regarding claim 14, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 1 (as described above).
Howell further teaches that the bioparticle is a cell or a non-cellular bioparticle (the setup is usable with non-cellular bioparticles as evidenced by its use with non-cellular particles. Note that intended use of a claimed device only limits the claim insofar as it restricts the structure of the device itself. See MPEP 2115. Additionally, the particles used are explicitly characterized as being in the size range of cells commonly studied by such devices.).
Also see claim 1 above regarding the biological nature of the bioparticle, where the kind of bioparticle Howell references is a cell.
Regarding claim 15, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 1 (as described above).
Howell further teaches that the at least one processor is further configured to irradiate a predetermined spot on the predetermined flow channel with the light (FIG. 2 C, region of interest labeled ROI), and the bioparticle moves in the predetermined flow channel so as to pass through the predetermined spot (the flow has to pass through the ROI to get from the input port of the flow channel located at the center of the spiral to the output ports. Also note that measurements are made there.).
Regarding claim 16, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 1 (as described above).
Howell further teaches that the bioparticle is labeled with one or more fluorescent dyes (section Bead preparation), the at least one processor is further configured to irradiate the bioparticle with the light including excitation light in one or more wavelength ranges (abstract, a microscope arc lamp of a standard fluorescence microscope is used for fluorescence imaging. Fluorescence imaging requires irradiating the image target with excitation light in one or more wavelength ranges.) and detect a luminance change as an event (FIG. 1).
Howell does not explicitly teach a spectroscopic optical system that disperses light emitted from the bioparticle.
In the same field of endeavor of fluorescent imaging flow cytometry, Ortyn teaches a spectroscopic optical system that disperses light emitted from the bioparticle (FIG. 25, dichroic filters 301-305) and a detection unit detecting each of the beams of light dispersed by the spectroscopic optical system (FIG. 25, detectors 321-325 collectively). By using dispersive optics, Ortyn distinguishes between multiple fluorescence colors, which can come from multiple dyes.
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 event-based imaging flow cytometer of Howell with the dispersive optics of Ortyn to gain the benefit of using multiple fluorescent dyes to mark particles under study to distinguish them.
Regarding claim 17, Howell, as modified by Ortyn and Kaduchak, teaches or renders obvious the biological sample analysis system according to claim 16 (as described above).
Howell does not explicitly teach the use of a plurality of sensors.
In the same field of endeavor of fluorescent imaging flow cytometry, Ortyn teaches a plurality of sensors disposed for the beams of light dispersed by the spectroscopic optical system on a one-to-one basis (FIG. 25, detectors 321-325). Using multiple detectors allows Ortyn to detect images independently for each of the dispersed beams.
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 event-based imaging flow cytometer of Howell with the multiple sensors of Ortyn to gain the benefit of capturing multiple images simultaneously.
Regarding claim 18, Howell teaches an information processing device including at least one processor (section Imaging setup, third paragraph, the computer running MATLAB) configured to:
generate subject information regarding a subject (by running MATLAB) on a basis of an event detected in each of a plurality of pixels that detects a luminance change of light from the subject as the event in a detection unit including the pixels (FIG. 1); and
a flow channel (FIG. 2 C) wherein the flow channel is with a width of 1 mm or less (section Results, first paragraph, specifies a channel with widths of 360 µm and 60 µm along its two cross-sectional axes. Also see FIG. 3, which has a 200 µm scale bar. Comparing the length of the scale bar to the width of the channel even at the right-hand edge of the region of interest, the channel is only about half a mm wide).
While the flow channel disclosed by Howell is spiraled rather than straight, Howell does contemplate the use of sensor systems like the one Howell used with other channel designs (COL. 3, sentences 1-2), and the main purpose of Howell appears to be developing event-based imaging as a means to study microfluidics, describing the experiments presented as a “proof-of-principle” (abstract, sentence 6), rather than in inertially separating polystyrene beads with a spiral-shaped flow channel.
In the same field of endeavor of imaging and analyzing small moving objects, such as cells, Ortyn does teach a straight flow cell (FIG. 25, flow cell 306). By not including the spiral like that of Howell, Ortyn avoids the inertial separation of the particles across the fluid stream, allowing the whole width of the flow channel to be used for all sizes of particles. Note that it is generally considered obvious, when a particular function is not desired, to remove both an element (such as the curvature of a flow channel) and its undesired function (such as inertial particle separation). See MPEP 2144.04 II A.
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 event-based imaging flow cytometer of Howell without straight the spiral of the flow cell, following the example of Ortyn, to avoid inertial particle separation if one does not consider inertial particle separation to be a desired function, for example, to more efficiently use the entire width of the flow cell for imaging of particles of all sizes. Note that Ortyn also describes the use of cells, a type of bioparticle, in the sample (abstract).
While Howell does discuss sorting of particles, it is in the context of using a spiral-shaped or otherwise curved flow channel to perform inertial separation of the particles, which is different from using bioparticle information generated by a processor to perform sorting in a straight channel as claimed, so Howell does not teach a claimed way to sort the bioparticle on the basis of the generated bioparticle information. Likewise, Ortyn provides a motivation to sort cells (a type of bioparticle) as background to their invention, but does not teach a particular way of doing the sorting itself (even if the imaging techniques of Ortyn would be useful as part of a cell sorting device).
In the same field of endeavor of imaging flow cytometry, Kaduchak teaches a device to sort the bioparticle on the basis of the generated bioparticle information (FIG. 7, sorting module 790, positioned downstream of the image detector 774 and described in paragraph 82). By including a sorting module, Kaduchak is able to separate the particles based on information gathered about them, such as cellular functions (paragraph 82).
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 event-based imaging flow cytometer of Howell, as modified by Ortyn, to sort the particles after they are imaged in the manner of Kaduchak, to gain the predictable benefit of being able to perform high-speed sorting of cells or other bioparticles as motivated by Ortyn.
Regarding claim 19, Howell teaches an information processing method including generating subject information regarding a subject (section Imaging setup, third paragraph, running the MATLAB imaging pipeline) as the subject flows through a predetermined flow channel (FIG. 2 C), on a basis of an event detected in each of a plurality of pixels that detects a luminance change of light from the subject as the event in a detection unit including the pixels (FIG. 1).
While the flow channel disclosed by Howell is spiraled rather than straight, Howell does contemplate the use of sensor systems like the one Howell used with other channel designs (COL. 3, sentences 1-2), and the main purpose of Howell appears to be developing event-based imaging as a means to study microfluidics, describing the experiments presented as a “proof-of-principle” (abstract, sentence 6), rather than in inertially separating polystyrene beads with a spiral-shaped flow channel.
In the same field of endeavor of imaging and analyzing small moving objects, such as cells, Ortyn does teach a straight flow cell (FIG. 25, flow cell 306). By not including the spiral like that of Howell, Ortyn avoids the inertial separation of the particles across the fluid stream, allowing the whole width of the flow channel to be used for all sizes of particles. Note that it is generally considered obvious, when a particular function is not desired, to remove both an element (such as the curvature of a flow channel) and its undesired function (such as inertial particle separation). See MPEP 2144.04 II A.
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 event-based imaging flow cytometry method of Howell without straight the spiral of the flow cell, following the example of Ortyn, to avoid inertial particle separation if one does not consider inertial particle separation to be a desired function, for example, to more efficiently use the entire width of the flow cell for imaging of particles of all sizes. Note that Ortyn also describes the use of cells, a type of bioparticle, in the sample (abstract).
While Howell does discuss sorting of particles, it is in the context of using a spiral-shaped or otherwise curved flow channel to perform inertial separation of the particles, which is different from using bioparticle information generated by a processor to perform sorting in a straight channel as claimed, so Howell does not teach a claimed way to sort the bioparticle on the basis of the generated bioparticle information. Likewise, Ortyn provides a motivation to sort cells (a type of bioparticle) as background to their invention, but does not teach a particular way of doing the sorting itself (even if the imaging techniques of Ortyn would be useful as part of a cell sorting device).
In the same field of endeavor of imaging flow cytometry, Kaduchak teaches a device to sort the bioparticle on the basis of the generated bioparticle information (FIG. 7, sorting module 790, positioned downstream of the image detector 774 and described in paragraph 82). By including a sorting module, Kaduchak is able to separate the particles based on information gathered about them, such as cellular functions (paragraph 82).
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 event-based imaging flow cytometer of Howell, as modified by Ortyn, to sort the particles after they are imaged in the manner of Kaduchak, to gain the predictable benefit of being able to perform high-speed sorting of cells or other bioparticles as motivated by Ortyn.
Regarding claim 20, Howell teaches a biological sample analysis method including:
irradiating a bioparticle in a biological sample with light (FIG. 2 A, Illumination. Note that intending to use an irradiation unit to illuminate a bioparticle in a biological sample does not impose a structural requirement on the irradiation unit that would distinguish that irradiation unit from one used to illuminate a nonbiological particle of similar size in a non-biological fluid) wherein the bioparticle flows through a flow channel wherein the flow channel is with a width of 1 mm or less (section Results, first paragraph, specifies a channel with widths of 360 µm and 60 µm along its two cross-sectional axes. Also see FIG. 3, which has a 200 µm scale bar. Comparing the length of the scale bar to the width of the channel even at the right-hand edge of the region of interest, the channel is only about half a mm wide);
detecting, as an event, a luminance change of light emitted from the bioparticle by irradiation with the light in each of a plurality of pixels (FIG. 1 demonstrates the function of an event-based camera); and
generating bioparticle information regarding the bioparticle on a basis of the event detected by each of the pixels (section Imaging setup, third paragraph, running the MATLAB imaging pipeline).
While Howell does not explicitly describe the samples used as biological samples, nor the micrometer-scale polystyrene beads therein as bioparticles, Howell does explicitly state that their results “confirm that event-based cameras can be used to track individual particle behaviours in the size range of commonly used biological cells” (section Particle tracking and velocity mapping, fourth paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the event-based imaging flow cytometer of Howell with bioparticles, such as cells, in the manner that Howell contemplated.
While the flow channel disclosed by Howell is spiraled rather than straight, Howell does contemplate the use of sensor systems like the one Howell used with other channel designs (COL. 3, sentences 1-2), and the main purpose of Howell appears to be developing event-based imaging as a means to study microfluidics, describing the experiments presented as a “proof-of-principle” (abstract, sentence 6), rather than in inertially separating polystyrene beads with a spiral-shaped flow channel.
In the same field of endeavor of imaging and analyzing small moving objects, such as cells, Ortyn does teach a straight flow cell (FIG. 25, flow cell 306). By not including the spiral like that of Howell, Ortyn avoids the inertial separation of the particles across the fluid stream, allowing the whole width of the flow channel to be used for all sizes of particles. Note that it is generally considered obvious, when a particular function is not desired, to remove both an element (such as the curvature of a flow channel) and its undesired function (such as inertial particle separation). See MPEP 2144.04 II A.
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 event-based imaging flow cytometry method of Howell without straight the spiral of the flow cell, following the example of Ortyn, to avoid inertial particle separation if one does not consider inertial particle separation to be a desired function, for example, to more efficiently use the entire width of the flow cell for imaging of particles of all sizes. Note that Ortyn also describes the use of cells, a type of bioparticle, in the sample (abstract).
While Howell does discuss sorting of particles, it is in the context of using a spiral-shaped or otherwise curved flow channel to perform inertial separation of the particles, which is different from using bioparticle information generated by a processor to perform sorting in a straight channel as claimed, so Howell does not teach a claimed way to sort the bioparticle on the basis of the generated bioparticle information. Likewise, Ortyn provides a motivation to sort cells (a type of bioparticle) as background to their invention, but does not teach a particular way of doing the sorting itself (even if the imaging techniques of Ortyn would be useful as part of a cell sorting device).
In the same field of endeavor of imaging flow cytometry, Kaduchak teaches a device to sort the bioparticle on the basis of the generated bioparticle information (FIG. 7, sorting module 790, positioned downstream of the image detector 774 and described in paragraph 82). By including a sorting module, Kaduchak is able to separate the particles based on information gathered about them, such as cellular functions (paragraph 82).
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 event-based imaging flow cytometry method of Howell, as modified by Ortyn, to sort the particles after they are imaged in the manner of Kaduchak, to gain the predictable benefit of being able to perform high-speed sorting of cells or other bioparticles as motivated by Ortyn.
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.
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/PAUL SCHNASE/Examiner, Art Unit 2877
/Kara E. Geisel/Supervisory Patent Examiner, Art Unit 2877
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