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 .
Election/Restrictions
Applicant’s election without traverse of claims Group II, claims 18-45 in the reply filed on 06/15/26 is acknowledged. However, in the amendment, claims 18-19 are withdrawn as well. It is unclear if this is intentional. Affirmation is required in response to this Office Action. For purpose of examination, claims 18-19 are examined herein.
Claim Objections
Claim(s) 32 is/are objected to because of the following informalities:
“a function of derived” should be “a function of derived image”. It appears the term “image” may have been accidentally deleted when applicant amended the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 18-26 and 37-45 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Du (EP 3230717 A2) as cited in previous Office Action.
Regarding claims 18-19, Du discloses a method for using a microfluidic system (240, Fig. 2D), comprising collecting in a selective manner cells chosen tumour cells, spermatozoa, liposomes, micro-beads, and extracellular vesicles (para. [0062]) in a forensic medicine, the device comprises:
at least one inlet (242, Fig. 2C, para. [0123]), through which, in use, the sample is inserted in the microfluidic system (the ports 242 are connected to the channel 122 and allow a fluidic medium 180 to be introduced, para. [0123]); and
a moving assembly, which comprises at least one microfluidic chamber (channel 122, Fig. 1) and is configured to move at least one specific particle inside the microfluidic chamber;
the moving assembly comprises: at least one actuator (motive module 162 and tilting module 166, Fig. 1 para. [0080], [0089]), which is configured to move said at least one specific particle inside the microfluidic chamber;
a detection device (imaging module 164, Fig. 1 para. [0086]), which is configured to acquire images of the microfluidic chamber; and
a control device (master control 154, see Figure 1), which is configured to control said at least one actuator (See the control diagram in Fig. 1) so as to move said at least one specific particle along a given path inside said microfluidic chamber (flow path of the microfluidic device, para. [00169]);
the control device develops at least one derived image as a function of said first image and on said second image (para. [00170]-[00171]) wherein the moving assembly is configured to move said at least one specific particle in a deterministic manner (The term "deterministic" does not automatically imply that one particle is moved independently of the others.) (a motive module 162 for controlling movement and/or selection of micro-objects (not shown) and/or medium (e.g., droplets of medium) in the microfluidic circuit 120, para. [0086]); and wherein the control device is configured to determine the type and/or group of said at least one specific particle as a function of said image (Various methods may be used to analyze the set of pixel clusters including traditional machine learning techniques where the above- discussed features are computed for a set of images of micro-objects and used to train a classifier to identify micro-objects of interest in new images based on the same features. Para. [00178]).
Regarding claim 20, Du discloses a method for isolation and/or analysis of a sample by means of a microfluidic system (240, Fig. 2D) for the manipulation (in particular, for the isolation) and/or the analysis of particles of a sample (para. [0122]);
the microfluidic system comprising at least one inlet (242, Fig. 2C, para. [0123]), through which, in use, the sample is inserted in the microfluidic system (the ports 242 are connected to the channel 122 and allow a fluidic medium 180 to be introduced, para. [0123]); and
a moving assembly, which comprises at least one microfluidic chamber (channel 122, Fig. 1) and is configured to move at least one specific particle inside the microfluidic chamber;
the moving assembly comprises: at least one actuator (motive module 162 and tilting module 166, Fig. 1 para. [0080], [0089]), which is configured to move said at least one specific particle inside the microfluidic chamber;
a detection device (imaging module 164, Fig. 1 para. [0086]), which is configured to acquire images of the microfluidic chamber; and
a control device (master control 154, see Figure 1), which is configured to control said at least one actuator (See the control diagram in Fig. 1) so as to move said at least one specific particle along a given path inside said microfluidic chamber (flow path of the microfluidic device, para. [00169]);
the method comprises:
a first detection step, during which said detection device acquires a first image of at least one part of the microfluidic chamber in a first instant, when said at least one specific particle is arranged in a first position of the given path inside said at least one part of the microfluidic chamber (first image, para. [0168]-[0169]);
a second detection step, during which said detection device acquires a second image of at least one area of the microfluidic chamber in a second instant subsequent to the first instant, when said at least one specific particle is arranged in a second position of the given path inside said at least one area of the microfluidic chamber (In certain instances, actions may be taken to induce movement of the fluid in the microfluidic device after creating the first image and prior to creating the second image. In these instances, inducing movement of the fluid present in the region can involve inducing a small, controlled flow of fluid into or out of the microfluidic device. para. [00169]);
a processing step, during which the control device develops at least one derived image as a function of said first image and on said second image (para. [00170]-[00171]) wherein the moving assembly is configured to move said at least one specific particle in a deterministic manner (The term "deterministic" does not automatically imply that one particle is moved independently of the others.) (a motive module 162 for controlling movement and/or selection of micro-objects (not shown) and/or medium (e.g., droplets of medium) in the microfluidic circuit 120, para. [0086]).
Regarding claim 21, Du discloses the claimed invention as discussed above in claim 20. Du discloses the method comprising an identification step, during which the control device estimates said second position of said at least one specific particle based on the derived image; said second position being different from the first position (Thus, in embodiments that use a differential image to identify micro-objects of interest, pixels identified as positive-value pixels can represent the current location of a micro-object (i.e., the position after movement of the fluid), and pixels identified as negative-value pixels can represent the former location of a micro-object (i.e., the position before movement of the fluid). Para. [00176]).
Regarding claim 22, Du discloses the claimed invention as discussed above in claim 20, wherein the moving assembly moves said at least one specific particle in a substantially selective manner relative to other particles of the sample inside the microfluidic chamber (a motive module 162 for controlling movement and/or selection of micro-objects (not shown) and/or medium (e.g., droplets of medium) in the microfluidic circuit 120, para. [0086]).
Regarding claim 23, Du discloses the claimed invention as discussed above in claim 20. Du discloses during the processing step, the control device develops the derived image as a function of the difference and/or subtraction between said first image and said second image (para. [00172]);
the method further comprises a moving step, during which said control device controls said at least one actuator in a third instant, which is subsequent to the first instant and prior to the second instant, so as to move said at least one specific particle from said first position along the give path (motive module 162, Fig. 1 para. [0080], [0089], [00164]).
Regarding claim 24, Du discloses the claimed invention as discussed above in claim 20. Du discloses providing to transfer at least part of the particles including at least one specific particle of a given type of the sample from said microfluidic chamber to a recovery chamber (sequestration pens 124, 126, 128, 130, Fig. 1) of the microfluidic system in a substantially selective manner to further particles of the sample (motive module 162 can control the activation of electrodes and/or transistors (e.g., phototransistors) to select and move micro-objects (not shown) and/or droplets of medium (not shown) in the flow path 106 and/or sequestration pens 124, 126, 128, 130. Para. [0089]).
Regarding claim 25, Du discloses the claimed invention as discussed above in claim 20. Du discloses during the first detection step and during the second detection step, said at least one part of the microfluidic chamber and said at least one area of the microfluidic chamber (structured light on at least a first region and unstructured light on at least a second region of the microfluidic device, para. [00157], respectively, are lighted with radiation having given wavelengths (First light source, para. [0158] and second light source, para. [0159]); said first and said second image are acquired at said given wavelength (In certain embodiments, imaging device 194 is configured to use at least two light sources...In these embodiments, the motive module 162 can be used to control the first light source 404 and the imaging module 164 can be used to control the second light source 432. para. [00157]).
Regarding claim 26, Du discloses the claimed invention as discussed above in claim 20. Du discloses an adjustment step, during which the control device defines at least one further given path (para. [00186]) for at least one further specific particle of the sample as a function of the derived image (In such embodiments, a single positive-value (or negative value) pixel can represent the location of a micro-object. Thus, in embodiments that use a differential image to identify micro-objects of interest, pixels identified as positive-value pixels can represent the current location of a micro-object (i.e., the position after movement of the fluid), para. [00176]); the moving assembly moves said further specific particle along said further given path (the tilting module 166 can control the tilting rate and timing to optimize transfer of micro-objects to the one or more sequestration pens via gravitational forces. The tilting module 166 is communicatively coupled with the imaging module 164…para. [0091]) so as not to hit said at least one specific particle; and, when the second position coincides with the first position or does not coincide with an expected position, the control device determines the second position as a function of the derived image and defines said further given path so that further given path does not go through the second position (In this embodiment, when the optimal trajectory for a first micro-objects intersects with the optimal trajectory for a second micro-objects, the optimal trajectory for the first micro-object is assigned to the second micro- object and the optimal trajectory for the second micro-object is assigned to the first micro- object. In another specific embodiment, the algorithm delays the repositioning of the first micro-object until such a time that the first and second micro-objects can move along their respective trajectories without colliding. Para. [00189]).
Regarding claim 37, Du discloses the claimed invention as discussed above in claim 20. Du discloses:
a plurality of further first detection step, during which said detection device acquires further first images of the microfluidic chamber in further first instants (first image, para. [0168]-[0169]), when a second particle is arranged in respective first positions of second given paths inside the microfluidic chamber (In this embodiment, when the optimal trajectory for a first micro-objects intersects with the optimal trajectory for a second micro-objects, the optimal trajectory for the first micro-object is assigned to the second micro- object and the optimal trajectory for the second micro-object is assigned to the first micro-object; para. [00189]. To determines the optimal trajectory to avoid collision and having the objects move in parallel, the algorithm would first need to acquired differential images of both first and second particle. Similar reasoning applies to the plurality of second detection steps below);
a plurality of second detection steps, during which said detection device acquires further second images of the microfluidic chamber in further second instants subsequent to the first instant, when said second particle is arranged in respective further second positions of the second given path inside the microfluidic chamber (In certain instances, actions may be taken to induce movement of the fluid in the microfluidic device after creating the first image and prior to creating the second image. In these instances, inducing movement of the fluid present in the region can involve inducing a small, controlled flow of fluid into or out of the microfluidic device. para. [00169]);
a plurality of further processing steps, during which the control device develops of plurality of further derived images, each as a function of a said further first image and of a said further second image (para. [00170]-[00171]) wherein the moving assembly is configured to move said at least one specific particle in a deterministic manner (The term "deterministic" does not automatically imply that one particle is moved independently of the others.) (a motive module 162 for controlling movement and/or selection of micro-objects (not shown) and/or medium (e.g., droplets of medium) in the microfluidic circuit 120, para. [0086]); and
a characterization step, during which said specific particle and said second specific particles are divided, in a classified manner, into at least two typological groups (density value) (In various embodiments, the method further comprises computing a density value associated with the set of micro-objects and computing the one or more trajectories based, at least in part, on the density value associated with the set of micro-objects…one or more trajectories connecting the sequestration pen with one or more micro-objects of the set of micro-objects. Para. [0024]).
Regarding claim 38, Du discloses the claimed invention as discussed above in claim 20. Du discloses a moving step, during which said control device controls said at least one actuator in a third instant, which is subsequent to the first instant and prior to the second instant, so as to move said at least one specific particle and a plurality of other particles during the moving step (motive module 162, Fig. 1 para. [0080], [0089], [00164]), the largest part of the at least one actuator of the moving assembly is controlled so that a plurality of other particles move (pump, para. [00169]); said first image also contains said other particles in respective initial positions (para. [00170]; said second image (para. [00170]) also contains said other particles in respective following positions (In some embodiments, modified light cages are used to reposition micro-objects iteratively or sequentially. In addition, modified light cages may be used to pen micro-objects in their assigned sequestration pens. In some embodiments, micro-objects that are closest to the perimeter of the spatial area or closest together in space may be re-positioned or penned prior to repositioning or penning other micro-objects. Para. [00195]).
Regarding claim 39, Du discloses the claimed invention as discussed above in claim 20. Du discloses the moving assembly is configured to move a plurality of particles inside the microfluidic chamber; the control device is configured to control said at least one actuator so as to move said plurality of particles inside said microfluidic chamber (motive module 162 and tilting module 166, Fig. 1 para. [0080], [0089]);
the method comprises:
a plurality of the first detection steps, during each of which said detection device acquires a respective first image of a respective part of the microfluidic chamber so that the first images contain a representation of said plurality of particles (first image, para. [0168]-[0169]);
a characterization step, during which the control device identifies which particles of said plurality of particles are of a given type and/or group (“assignment” interpreted as type/group; Various combinatorial algorithms may be used to compute the optimal assignment between micro-objects and sequestration pens. Suitable algorithms include: greedy algorithms, nonlinear optimization, heuristic-based algorithms and constrained search. Other similar algorithms are known in the art. Para. [00187]) as a function of said further first images (para. [00171]-[00172] and [00174];
a transfer step, during which at least one particle of a given type and/or group, which was identified as such during the characterization step, is transferred by means of the moving assembly from said microfluidic chamber to a recovery chamber of the microfluidic system in a substantially selective manner relative to further particles of the sample (In this embodiment, when the optimal trajectory for a first micro-objects intersects with the optimal trajectory for a second micro-objects, the optimal trajectory for the first micro-object is assigned to the second micro- object and the optimal trajectory for the second micro-object is assigned to the first micro-object; para. [00189]; at least part of the characterization step and at least part of the transfer step take place simultaneously or before the at least part of plurality of detection steps (Depending on the embodiment, the modified light cages for two proximate micro-objects are used to reposition the micro-objects prior to, or after, computing and selecting the trajectory and assignment to a sequestration pen for each micro-object. Para. [00195]; Process is being done sequentially so one object may be in detection step, while another object is in transfer step).
Regarding claim 40, Du discloses the claimed invention as discussed above in claim 39. Du discloses the at least one particle of the given type and/or group is transferred towards the recovery chamber by means of the moving assembly during or before one of said first detection steps (Depending on the embodiment, the modified light cages for two proximate micro-objects are used to reposition the micro-objects prior to, or after, computing and selecting the trajectory and assignment to a sequestration pen for each micro-object. para. [00195]; Process is being done sequentially so one object may be in detection step, while another object is in transfer step).
Regarding claim 41, Du discloses the claimed invention as discussed above in claim 39. Du discloses
a plurality of the second detection steps, each of which is subsequent to a respective first detection step and during each of which said detection device acquires a respective second image of the part of the microfluidic chamber acquired during the respective first detection step so that the second images contain a representation of said plurality of particles (second image, para. [0169]-[0170]);
a plurality of moving steps, each of which is subsequent to a respective first detection step and prior to a respective second detection step and during which said control device controls said at least one actuator so as to move at least part of said plurality of particles arranged in the area of the part of the microfluidic chamber acquired during the respective first detection step (Depending on the embodiment, the modified light cages for two proximate micro-objects are used to reposition the micro-objects prior to, or after, computing and selecting the trajectory and assignment to a sequestration pen for each micro-object. para. [00195]; Process is being done sequentially so one object may be in detection step, while another object is in transfer step).; and
a processing step, during which the control device develops a plurality of derived images, each as a function of one of the first images and on a corresponding one of the second images (para. [00170]-[00171]);
during said characterization step, the control device identifies which particles of said plurality of particles are of a given type and/or group as a function of said first images (a derived image based on first and second image would still be considered a function of first image; (Para. [00178]);
a second image corresponds to a first image when said second image and said first image are of the same part of the microfluidic chamber (para. [0003]-[0007] disclose first and second image are taken in same region of the device).
Regarding claim 42, Du discloses the claimed invention as discussed above in claim 20. Du discloses the moving assembly moves said at least one specific particle in a substantially selective manner relative to other particles of the sample inside the microfluidic chamber (In some embodiments, modified light cages are used to reposition micro-objects iteratively or sequentially. In addition, modified light cages may be used to pen micro-objects in their assigned sequestration pens. In some embodiments, micro-objects that are closest to the perimeter of the spatial area or closest together in space may be re-positioned or penned prior to repositioning or penning other micro-objects. Para. [0195]).
Regarding claim 43, Du discloses the claimed invention as discussed above in claim 20. Du discloses during the moving step, the moving assembly exerts a force directly on said at least one specific particle (Sequestration pens in accordance with the present invention can comprise various shapes, surfaces and features that are optimized for use with DEP, OET, OEW, and/or gravitational forces, para. [0092]).
Regarding claim 44, Du discloses the claimed invention as discussed above in claim 20. Du discloses the moving assembly exerts a force directly on said at least one specific particle during the first and the second detection step ( In other embodiments, optoelectrowetting (OEW) forces are applied to one or more positions in the support structure 104 (and/or the cover 110) of the microfluidic device 100 (e.g., positions helping to define the flow path and/or the sequestration pens) via one or more electrodes (not shown) to manipulate, transport, separate and sort droplets located in the microfluidic circuit 120. Para. [0099]. Note: a force is exerted on a particle when the particle moves between two positions during the two detection steps).
Regarding claim 45, Du discloses the claimed invention as discussed above in claim 44. Du discloses the moving assembly exerts a force directly on said at least one specific particle during the first and the second detection step as to keep at least one specific particle suspended (In some embodiments, OEW forces are used to prevent a droplet within a sequestration pen (e.g., sequestration pen 124, 126, 128, or 130) from being displaced therefrom. Para. [0099]) while said first image and said second image are acquired (a specific particle may be kept in place in sequestration pen, while first and second image are being taken for other particles in the system).
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(s) 27-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Du (EP 3230717 A2) in view of Wang (WO2002087792A1) as cited in IDS filed on 11/172023.
Regarding claim 27, Du discloses the claimed invention as discussed above in claim 20. Du does not disclose the claimed speed estimation step. Du discloses the speed of the objects can be controlled and gradually “ramped up or down” (para. [0196]).
In an analogous art, Wang discloses a method for isolation and/or analysis of a sample by means of a microfluidic system (Fig. 14-15) for the manipulation and/or the analysis of particles of a sample (para. [0122]-[0124]);
the microfluidic system comprising at least one inlet (para. [0126]-[0127] and [0151]), through which, in use, the sample is inserted in the microfluidic system (para. [0151]); and
a moving assembly (Fig. 9A), which comprises at least one microfluidic chamber and is configured to move at least one specific particle inside the microfluidic chamber (the chamber housing the “optical gradient fields”, para. [0212] and [0214] and Fig. 12);
the moving assembly comprises: at least one actuator (actuator 286, Fig. 9), which is configured to move said at least one specific particle inside the microfluidic chamber (para. [0079]);
a detection device (camera, para. [0231]), which is configured to acquire images of the microfluidic chamber; and
a control device (control system 64, Fig. 3), which is configured to control said at least one actuator so as to move said at least one specific particle along a given path inside said microfluidic chamber (The control system 64 is connected to the phase modulator 62 so as to cause the pattern 72 to move relative to the objects within the system 50, such as the sample plate 70., para. [0094]); and a method of estimating the speed of particle as a function the distance between first position and second position and time needed to travel the distance (The absence of motion, or the presence of motion (amount of motion, direction of motion, speed of motion, etc.) may be utilized to characterize, or analyze the particle or particles. In certain applications, it may be sufficient to determine the response of a single particle to a particular optical pattern. Thus, information may be derived about the particle merely from the fact that the particle moved, or moved in a particular way or by a particular amount. Para. [0116] and Fig. 35).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have reconfigured the master control of Du to include an algorithm for estimating the speed/velocity of the particle from Wang to derive the claimed invention. Doing so allows particle speed or escape velocity to be used as a characteristic for sorting/separating the particles (In yet other applications, it is desirable to separate two or more particles. In that case, by comparing the position of the particles relative to each other such as in FIG. 12A versus 12B, information regarding the particle may be obtained. Wang, Para. [0116] and Fig. 35).
Regarding claim 28, Modified Du discloses the claimed invention as discussed above in claim 27. While neither Du nor Wang explicitly discloses the claimed supplementary detection steps for acquires supplementary images for speed estimation, both Du and Wang, however, discloses a differential images technique in which the camera is configured to take picture at a first instant and second instant, with the resultant image (obtained by subtracting the image of a first instant from the second instant) illustrates a shift in position of the particle (Wang, para. [0231] and Du, para. [0086] and [0169]). As such, it would have been obvious to one of ordinary skill in the art before the effective filing date to have realized that the speed estimation, which involves determining the shift in position in a time frame, of Wang from claim 27 involves incorporating differential images technique of either Wang or Du to derive the claimed supplementary detection steps.
Regarding claim 29, Modified Du discloses the claimed invention as discussed above in claim 27. Wang, after incorporation with Du, discloses a convey step, during which the moving assembly moves said at least one specific particle along said given path as a function of said detected speed (In Fig. 5A, the translation speed of the potential energy waves may be set to be larger than the speed at which particle 1 310 may move forward through the medium in which it is located. Para. [0118]; When using a moving optical gradient field, the motion may be at a constant velocity (speed and direction), or may vary in a linear or non-linear manner. Para. [0120]) for effective separation (By selection of the speed, orientation, periodicity, intensity and other parameters of the optical force gradient, the particles may be effectively separated. Para. [0124]).
Regarding claim 30, Modified Du discloses the claimed invention as discussed above in claim 27. Wang, after incorporation with Du, discloses a characterization step, during which the type and/or group of said at least one specific particle is determined by the control device as a function of the detected speed (The absence of motion, or the presence of motion (amount of motion, direction of motion, speed of motion, etc.) may be utilized to characterize, or analyze the particle or particles. Para. [00116]).
Regarding claim 31, Modified Du discloses the claimed invention as discussed in claim 27. Du discloses
at least one further first detection step, during which said detection device acquires further first images of the microfluidic chamber in further first instants (first image, para. [0168]-[0169]), when a second particle is arranged in respective first positions of second given paths inside the microfluidic chamber (In this embodiment, when the optimal trajectory for a first micro-objects intersects with the optimal trajectory for a second micro-objects, the optimal trajectory for the first micro-object is assigned to the second micro- object and the optimal trajectory for the second micro-object is assigned to the first micro-object; para. [00189]. To determines the optimal trajectory to avoid collision and having the objects move in parallel, the algorithm would first need to acquired differential images of both first and second particle. Similar reasoning applies to the plurality of second detection steps below);
at least one further second detection step, during which said detection device acquires further second images of the microfluidic chamber in further second instants subsequent to the first instant, when said second particle is arranged in respective further second positions of the second given path inside the microfluidic chamber (In certain instances, actions may be taken to induce movement of the fluid in the microfluidic device after creating the first image and prior to creating the second image. In these instances, inducing movement of the fluid present in the region can involve inducing a small, controlled flow of fluid into or out of the microfluidic device. para. [00169]);
a further processing step, during which the control device develops at least one further derived image as a function of a said further first image and of a said further second image (para. [00170]-[00171]); and Wang, after incorporation with Du, discloses the method additionally comprises:
a further speed estimation step, during which the control device estimates a further detected speed of the second specific particle as a function the distance between first further position and second further position, obtained based on said further derived image, and on the time needed by the second specific particle to be moved from the further first position to the further second position (The absence of motion, or the presence of motion (amount of motion, direction of motion, speed of motion, etc.) may be utilized to characterize, or analyze the particle or particles. In certain applications, it may be sufficient to determine the response of a single particle to a particular optical pattern. Thus, information may be derived about the particle merely from the fact that the particle moved, or moved in a particular way or by a particular amount. Para. [0116] and Fig. 35);
a further conveying step, during which the moving assembly moves said second specific particle as a function of said detected speed along said second given path (In Fig. 5A, the translation speed of the potential energy waves may be set to be larger than the speed at which particle 1 310 may move forward through the medium in which it is located. Para. [0118]; When using a moving optical gradient field, the motion may be at a constant velocity (speed and direction), or may vary in a linear or non-linear manner. Para. [0120]) for effective separation (By selection of the speed, orientation, periodicity, intensity and other parameters of the optical force gradient, the particles may be effectively separated. Para. [0124]).
Regarding claim 32, Modified Du discloses the claimed invention as discussed above in claim 30. Du discloses the method further comprises a characterization step, during which the type and/or group of said at least one specific particle is determined (In addition to information specifying whether a micro-object is present, micro-object identification can provide various additional information. As discussed above, the differential and/or filtered image may be analyzed with respect to the size and shape of the potential micro- object. In doing so, various information regarding the micro-object may be produced including the radius of the micro-object, the perimeter of the micro-object and a centroid associated with the micro-object. para. [0180]).
Regarding claim 33, Modified Du discloses the claimed invention as discussed above in claim 32. Du discloses during characterization step, said control device determines the type and/or group of said at least one specific particle using an automated learning (Various methods may be used to analyze the set of pixel clusters including traditional machine learning techniques where the above- discussed features are computed for a set of images of micro-objects and used to train a classifier to identify micro-objects of interest in new images based on the same features. Para. [00178]).
Regarding claim 34, Modified Du discloses the claimed invention as discussed above in claim 32. Du discloses the method further comprises a learning step (para. [00178]), which comprises:
a step of acquiring images of micro-objects in the device (Various methods may be used to analyze the set of pixel clusters including traditional machine learning techniques where the above- discussed features are computed for a set of images of micro-objects… para. [00178]; and
at least one processing step during which the control device develops derived test image as function of said acquired images and determines parameters of an automated learning algorithm for the identification of the types of particles based on the derived test image (…and used to train a classifier to identify micro-objects of interest in new images based on the same features. Para. [00178]).
Furthermore, Du discloses a first detection step, during which said detection device acquires a first image of at least one part of the microfluidic chamber in a first instant, when said at least one specific particle is arranged in a first position of the given path inside said at least one part of the microfluidic chamber (first image, para. [0168]-[0169]); and
a second detection step, during which said detection device acquires a second image of at least one area of the microfluidic chamber in a second instant subsequent to the first instant, when said at least one specific particle is arranged in a second position of the given path inside said at least one area of the microfluidic chamber (In certain instances, actions may be taken to induce movement of the fluid in the microfluidic device after creating the first image and prior to creating the second image. In these instances, inducing movement of the fluid present in the region can involve inducing a small, controlled flow of fluid into or out of the microfluidic device. para. [00169]).
Neither Du nor Wang explicitly discloses the claimed detection sub-steps. However, the first and second learning images are essentially the same images similar to the images taken in claim 20 but specifically for the purpose of training a machine learning model. In addition, Du has already disclosed a method of training a machine learning and a processing step of classifying/identifying micro-objects of interest based on the new image acquired and images already presented in the model (para. [00178]). It would have been obvious to one of ordinary skill in the art before the effective filing date to implement the claimed detection and processing sub-steps in order to generate enough test images for the classification machine learning model taught by Du (para. [00178]).
Regarding claim 35, Modified Du discloses the claimed invention as discussed above in claim 32. Wang, after incorporation into Du, discloses one re-orientation and/or deformation step (a system for optical sorting based upon a physical parameter of the object, such as deformability. Para. [00140] and Fig. 24), during which said moving assembly re-orientates and/or deforms said at least one specific particle so that said at least one specific particle assumes a different conformation (…and characterizing the particle based at least in part upon reaction of the particle to the optical force, wherein the positions are the same, wherein the characterization includes a nonpositional parameter, wherein the non-positional parameter is rotation of the particle, claim 10); an additional detection step, during which said detection device acquires an additional image of the specific particle when said at least one specific particle has assumed said different conformation; during the processing step, the control device develops an additional derived image as a function of said additional image and one between first said image, said second image and a further additional image (para. [00231]; Wang discloses all monitoring is done by differential imaging technique which involves taking a “before” and “after” image); during the characterization step, the type and/or group of said at least one specific particle is determined also as a function of said additional derived image (Alternatively, the particles 502,504 may be subject to the optical force 500, and the structure of the particles 502,504 monitored. In that way, by observing the deformability of the particles, relative to the light pattern 500, the particles may be identified, classified or otherwise sorted. Para. [00140]).
Regarding claim 36, Modified Du discloses the claimed invention as discussed above in claim 32. Du discloses, during said characterization step, the respective type of each particle of a plurality of particles is determined as a function of said derived image (para. [00170]-[00171]) and at least one particle of a given type and/or group is identified (Para. [00178]); the method also comprises a transfer step, during which the at least one particle of a given type and/or group is transferred from said microfluidic chamber to a recovery chamber (sequestration pens 124, 126, 128, 130, Fig. 1) of the microfluidic system in a substantially selective manner relative to further particles of the sample (In some embodiments, modified light cages are used to reposition micro-objects iteratively or sequentially. In addition, modified light cages may be used to pen micro-objects in their assigned sequestration pens. In some embodiments, micro-objects that are closest to the perimeter of the spatial area or closest together in space may be re-positioned or penned prior to repositioning or penning other micro-objects. Para. [0195]).
Conclusion
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/M.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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