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 11/3/2025.
Response to Arguments
Rejections under 35 U.S.C. § 112
The rejections under 35 U.S.C. § 112 are overcome by amendment.
Prior Art Rejections
Applicant’s first argument is that Bernick does not teach the claimed first sensor unit, however, this argument is not persuasive. First, sensor 1024 does identify “positions of the dispersed objects in the sample fluid, including a position of a target object selected from the dispersed objects”, as any objects already taken up are those selected (by taking them up) and are in the sample fluid found in a particular compartment of sample fluid, identified as in the detection zone of sensor 1024. Nothing in the claim requires that the detection occur prior to take-up. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Second, detector 1830 and objective 1880 (both in FIG. 18) perform detection on targets not yet taken up via atomic force microscopy and optical microscopy, respectively, as described below.
Applicant’s second argument is that Bernick’s system, which can sample intracellular material, does not satisfy limitations regarding taking up microscopic objects dispersed across a support surface, however, this argument is not persuasive. When cells are dispersed across a support surface, taking up microscopic intracellular material falls within the broadest reasonable interpretation of taking up microscopic objects dispersed across that support surface, even if that intracellular material is additionally contained by the cell membranes. Further, as described in MPEP 2115, recitations of a material or article worked upon (such as intracellular vs extracellular microscopic objects) do not generally limit claims to an apparatus (such as a system for handling dispersed microscopic objects contained in a sample fluid), and it is unclear why Applicant would consider the sample probe of Bernick to not function for extracellular microscopic objects dispersed on a support surface or what language of the claim would disqualify intracellular material.
Applicant’s third argument is that sensors that perform operation on the fluid flowing through the microchannels of the device do not meet the limitations of claim 4 due to not recognizing targets outside of the device, however, this argument is not persuasive. The language of the claim as currently drafted does not require that the dispersed objects or targeted objects be identified before being taken up by the sample probe. Further, detector 1830 and objective 1880 (both in FIG. 18) perform identification on targets not yet taken up via atomic force microscopy and optical microscopy, respectively, as described below.
Applicant’s fourth argument is that Bernick does not teach a control unit configured to identify a target by an object recognition algorithm, however, this argument is not persuasive. Paragraph 66 describes a controller 1840, and standard AFM and optical microscopy are sufficient for object recognition algorithms at the claimed level of generality, which encompasses looking at the data (such as an optical or atomic force microscope view of an object) and mentally comparing what is seen to what the user has seen previously. Even if the claim strictly required that the object recognition algorithm be automated, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have automated the manual task of recognizing objects, absent more specifics, such as a non-obvious algorithm. See MPEP 2144.04 III.
Applicant’s fifth argument is that Bernick does not teach the claimed processing unit to adjust a travelling path between a pair of consecutive targets according to a distance between the pair of target objects, however, this argument is not persuasive. Paragraph 42 indicates that the probe can be moved from one target to the next with a multi-axis staging device, and it is unclear how anything could travel along a travelling path from an initial location to a destination in such a way that the travelling path is independent of the distance between the starting point and the destination.
Applicant’s sixth argument is that Bernick does not teach that the system can identify or calculate a distance between targets or move from one target to another simply by a user providing a distance, however, this argument is not persuasive. Such features are entirely absent from the claim, even as amended.
Applicant’s seventh argument is that Bernick does not teach a manipulation inlet to inject labeling agent (or other manipulation fluid) into the compartments of sample liquid, however, this argument is not persuasive. Bernick does teach such microchannels (FIG. 10, second microchannel 920).
Applicant’s eighth argument is that paragraph 65 of Bernick does not teach the limitations of claim 13, however, this argument is moot. The embodiment(s) disclosed in paragraph 65 are not relied on in the present action to teach the cited limitations.
Applicant’s ninth argument is that Bernick does not teach identifying the position of a target object before take-up, however, this argument is not persuasive. Bernick does teach such position identification (FIG. 18, optical microscope 1880 and detector 1830).
Applicant’s tenth argument is that Bernick does not teach elongated grooves, however, this argument is moot. The present action does not rely on Bernick to do so.
Applicant’s eleventh argument is that Bernick does not teach the cited portions of claim 18, however, this argument is moot. The new ground of rejection does not rely on any teaching challenged in this argument to teach the cited limitations.
Applicant’s twelfth argument is that Okano does not teach the cited portions of claim 5, however, this argument is moot. The new ground of rejection does not rely on any teaching challenged in this argument to teach the cited limitations.
Applicant’s thirteenth argument is that Okano does not teach the cited portions of claim 6, however, this argument is moot. The new ground of rejection does not rely on any teaching challenged in this argument to teach the cited limitations.
Applicant’s fourteenth argument is that Okano does not teach the cited portions of claim 19, however, this argument is moot. The new ground of rejection does not rely on any teaching challenged in this argument to teach the cited limitations.
Applicant’s fifteenth argument is that Bernick, as modified by Schober, fails to teach the limitations of claim 8 regarding an additional inlet and adding a particular flow rate Qadd, however, this argument is not persuasive. Bernick teaches an additional inlet (FIGs. 12-16, third microchannel 1204), as well as intermittently setting the claimed equality (paragraph 47, ceasing operation of the pumps sets the flow rates, including Qadd, equal to zero, as well as the difference between the flow rates in order to pause collection, such as to move the probe to collect a separate sample (paragraph 48)). Schober also teaches a more general condition for stopping intake, with input flow equaling output flow (paragraph 13), which satisfies the claimed equality in the case where an additional inlet is not active.
Applicant’s sixteenth argument is that Bernick, as modified by Schober, does not teach an additional inlet or the flow rate Qadd recited in claim 9, however, this argument is not persuasive. The claim limitations challenged by Applicant are exclusive to claim 8 and are not found in claim 9. A claim may only be novel and non-obvious based on its own limitations, including limitations inherited from each claim on which it depends, directly or indirectly, rather than on limitations from unrelated claims.
Applicant’s remaining arguments relate to rejections relying on Schober in view of Bernick, however, these arguments have been fully considered, but are moot. The present action does not rely on that combination of references in that order for any rejection.
As the independent claims are not allowable, the dependent claims are not automatically allowable.
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 12-14 and 18-19 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.
Regarding claim 12, while the open-ended language of claim 1, on which claim 12 depends, does not preclude the use of the system on more than one target object, the singular target object introduced in claim 1 does not provide adequate antecedent basis for the potential plurality of target objects denoted by “the target object(s)” as recited in claim 12. The claim is interpreted as referring to at least one target object including the target object.
Likewise, claim 13 recites “the one or more target objects” rather than “the target object” introduced in claim 1. The term in claim 13 lacks adequate antecedent basis for any additional target objects. The claim is interpreted as referring to at least one target object including the target object.
Claim 19 recites the limitation "the object(s)" in line 2. There is insufficient antecedent basis for this limitation in the claim. In particular, it is unclear if the claim is intending to refer to the dispersed objects, the target object, or a new object. The claim is interpreted as referring to an object, which may or may not be any of the previously introduced objects.
Claims 14 and 18 is indefinite for depending on indefinite claim 13 and failing to fix its indefiniteness.
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) 1-4, 6-12, and 15-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bernick (US patent publication 20140011226).
Regarding claim 1, Bernick teaches a system for handling dispersed microscopic objects contained in a sample fluid (FIG. 18, system 1800), comprising:
a first microfluidic device (FIG. 1, sample probe 100) comprising a microchannel with an inlet (FIG. 1, second port 132), an outlet (FIG. 1, first port 128) and an opening (FIG. 1, opening 124),
the opening being located between the inlet and the outlet (FIG. 1, note that the fluid traveling between the ports 132 and 128 must travel via opening 124);
a conveying device configured to pump a carrier fluid via the inlet into the microchannel with an input volumetric flow rate (Qin) (FIG. 1, controlled by second pump 148) and to remove fluid from the microchannel via the outlet with an output volumetric flow rate (Qout) (FIG. 1, controlled by first pump 144);
wherein the cross section of the opening is configured such that, if the opening is in the sample fluid, the following conditions are fulfilled:
a) if the input volumetric flow rate (Qin) is equal to the output volumetric flow rate (Qout), i.e. Qin= Qout, no carrier fluid emerges from the opening into the sample fluid and no sample fluid enters the microchannel (this situation is shown in several embodiments, including FIG. 4, where bulb 374 of isolator fluid blocks the opening so isolator fluid is moving through the system and no additional sample fluid is taken up, as does FIG. 6, representing a situation when the probe is moved from one sampling location to another),
b) if the output volumetric flow rate (Qout) is greater than the input volumetric flow rate (Qin), i.e. Qout> Qin, sample fluid enters the microchannel via the opening so that it is embedded as one or more compartments of sample fluid in the flow of the carrier fluid (FIG. 3 shows a situation when sample fluid is aspirated into the device. FIG. 5 shows the system with the sample fluid isolated in a compartment by the isolator fluid);
wherein the system is configured for a take-up mode in which, at least intermittently, the output volumetric flow rate (Qout) is greater than the input volumetric flow rate (Qin), i.e. Qout> Qin, so that the system provides a flow of carrier fluid from the inlet through the microchannel and past the opening to the outlet and sequentially takes up one or more compartments of sample fluid into the flow of the carrier fluid with a take-up volumetric flow rate (Qtakeup) (FIGs. 3-7 show a sequence of steps in this process, in which sample fluid is aspirated into the probe (FIG. 3) with Qout>Qin, the isolator fluid blocks the opening and is collected (FIG. 4), isolating the plug of sample fluid (FIG. 5), the probe is moved to another sample location (FIG. 6), and a second sample is taken sequentially in a separate compartment of the fluid flow (FIG. 7));
wherein the system further comprises:
a first sensor unit for identifying positions of the dispersed objects in the sample fluid, including a position of a target object selected from the dispersed objects (FIG. 18, both detector 1830, which uses atomic force microscopy, and objective 1880, which uses optical microscopy, can detect and identify targets dispersed in the sample fluid); and
a positioning unit configured to position the opening at a target position proximate to the position of the target object such that the target object is drawn into the microchannel together with a certain volume of sample fluid and thereby embedded with the sample fluid in the carrier fluid as a compartment (paragraph 42 describes a multi-axis staging device to move the device from one target to another. FIG. 7 shows multiple compartments of target objects that have been sampled. Note that recitations of a material or article (such as a particular type of dispersed object in a fluid) worked on by an apparatus (such as a system for handling dispersed microscopic objects contained in a sample fluid) do not generally limit claims to the apparatus. See MPEP 2115).
Regarding claim 2, Bernick teaches the system according to claim 1, wherein the system is configured to take up microscopic objects dispersed across a support surface, wherein the support surface is the bottom surface of a container in which the sample fluid is contained (paragraph 42, the bottom surface of the inside of a dish or multi-well plate supports the contents, and cells in different locations are dispersed. Intracellular material from different cells, which are dispersed across a surface, is itself dispersed across the surface, particularly the portions supporting those cells. Further, one of ordinary skill in the art would recognize that, while Bernick describes the use of the device in terms of intracellular material, the device is perfectly capable of collecting extracellular samples).
Regarding claim 3, Bernick teaches the system according to claim 1, wherein the system comprises a control unit (FIG. 18, system controller 1840).
Regarding claim 4, Bernick teaches the system according to the claim 3, wherein the control unit is configured to identify one or more target objects among the dispersed objects from first sensor data created by the first sensor unit by an object recognition algorithm (FIG. 10, sensor 1024 can be used to identify objects that have been targeted and collected from among the other dispersed objects, FIG. 18, detector 1830 can identify objects prior to take-up via atomic force microscopy, and objective 1880 can identify objects prior to take-up via optical microscopy. Note that viewing an optical or AFM image and recognizing the target object is an object recognition algorithm, falling well within the scope of the claim at the high level of generality at which the claim is written).
Regarding claim 6, Bernick teaches the system according to claim 3, wherein the positioning unit is configured to, at least intermittently, change a velocity at which the opening is moved (vopening) between a plurality of consecutive target objects during the take-up mode, wherein the velocity is adjusted according to a distance between each pair of consecutive target objects (paragraph 42 describes how the opening is moved with a suitable multi-axis staging device. Note that the change in position (i.e., displacement) of an object (e.g., an opening) is equal to an integral of the object’s velocity with respect to time (or, treating velocity changes as instantaneous, the sum of each velocity multiplied by how much time the object spends at that velocity). As a result, the velocity of an object as a function of time determines how far its destination is from its starting point. For example, a velocity profile that moves the probe 2 mm from a first target to a second target would inherently need to be adjusted to reach a third target 1 mm from the second (either moving at a lower speed or in a different set of directions at the same speed (following a less direct path) or adjusting both speed and direction of travel).
Regarding claim 7, Bernick teaches the system according to claim 3, wherein the positioning unit is configured to, at least intermittently, change a travel path of the opening between a pair of consecutive target objects during the take-up mode, wherein the travel path is adjusted according to a distance between the pair of target objects (paragraph 42 describes how the opening is moved with a suitable multi-axis staging device. Note that any given path inherently has its start and end a particular distance apart (with different paths often, but not always, having different distances). As a result, moving between two points separated by a distance inherently requires adjusting the travelling path according to a distance between the points).
Regarding claim 8, Bernick teaches the system according to claim 3, wherein the microchannel comprises one or more additional inlets for additionally providing a fluid via the one or more additional inlets to the microchannel at an additional volumetric flow rate (Qadd) (FIG. 12, third microchannel 1204, which may be used to add and additional flow of isolator fluid (paragraph 60)); and
wherein the control unit is configured, during take-up mode, to intermittently change the additional volumetric flow rate (Qadd) to be essentially equal to the absolute value of the difference (|Qin – Qout|) of the input volumetric flow rate (Qin) and the output volumetric flow rate (Qout) to prevent take-up of sample fluid through the opening (paragraph 60, penultimate sentence points out that the third channel 1204 may be used to sample multiple cells in the manner described elsewhere. Paragraph 47 points out that the probe is sometimes withdrawn after taking up a sample may be ceased and the plugs stored (held) in the microchannels. When the flow is stopped, the input volumetric flow rate Qin and the output volumetric flow rate Qout are both zero, so the absolute value of their difference is also zero. For the samples to be held, rather than moved along the microchannel, the third microchannel 1204 would have to also be stopped, with a flow rate equal to the (zero) flow rate difference between input and output).
Regarding claim 9, Bernick teaches the system according to claim 3, wherein the control unit is configured to intermittently vary the input volumetric flow rate (Qin) during take-up mode in order to prevent the formation of one or more empty compartments of sample fluid when the opening is not proximate to a particle or one or more particles proximate to the opening are not to be drawn into the microchannel (Paragraph 47 points out that the probe is sometimes withdrawn after taking up a sample may be ceased and the plugs stored (held) in the microchannels, varying the input volumetric flow rate from a nonzero value to a zero value).
Regarding claim 10, Bernick teaches the system according to claim 1, wherein the microchannel comprises a manipulation inlet arranged at the opening or between the opening and the outlet, and wherein the system is configured to deliver a manipulation fluid via the manipulation inlet into a respective compartment in the microchannel at a manipulation volumetric flow rate (Qmanip) (FIG. 10, second microchannel 920 or FIG. 11, third microchannel 1128, which are used to inject various materials into the samples collected) wherein the fluid delivered via the manipulation inlet is selected from one or a combination of: a gas to be metabolized by the objects, a liquid containing a growth stimulator for the objects, a liquid containing one or more type of bacteria, a liquid containing culture media composed of nutrition and pH-Buffer components, a liquid containing an enzyme, a liquid containing ingredients for digestion of the object, parts of the object or liberation of surface bound molecules, a liquid containing compounds for analytical assay purposes, a liquid containing a PCR mix, a liquid containing antibodies, a liquid containing nanomaterials for surface-enhanced Raman spectroscopy, a liquid containing particles (a liquid inherently contains particles, typically atoms. Also see paragraph 30 regarding solid particles carried by liquids), and a liquid containing marker substances (paragraph 55, a labeling agent is a marker substance).
Regarding claim 11, Bernick teaches the system according to claim 1, wherein the system comprises a container forming a support surface, wherein the system is configured to take up the microscopic objects when dispersed across the support surface, wherein the support surface comprises a structure for prearranging the microscopic objects, the structure comprising a plurality of wells (paragraph 42, multi-well plate, in which cells in different locations are dispersed. Intracellular material from different cells, which are dispersed across a surface, is itself dispersed across the surface, particularly the portions supporting those cells. Further, one of ordinary skill in the art would recognize that, while Bernick describes the use of the device in terms of intracellular material, the device is perfectly capable of collecting extracellular samples).
Regarding claim 12, Bernick teaches the system according to claim 1, the system comprising a storage configured to accommodate the target object(s) while embedded with the sample fluid in the carrier fluid for one or more of storage, cultivation and further treatment of the target object(s), wherein the one or more of storage, cultivation and further treatment of the target object(s) occurs within a microchannel (paragraphs 42 and 47 point out that the samples may be stored in the microchannels 116 and 120).
Regarding claim 15, Bernick teaches a method for picking microscopic objects by suction, comprising the steps:
a) providing a sample of dispersed microscopic objects contained in a sample fluid (FIG. 18, contained in cell holder 1870, as described in paragraph 66);
b) providing a first microfluidic device (FIG. 1, sample probe 100) comprising a microchannel with an inlet (FIG. 1, second port 132), an outlet (FIG. 1, first port 128) and an opening located between the inlet and the outlet (FIG. 1, opening 124, note that the fluid traveling between the ports 132 and 128 must travel via opening 124);
c) providing a carrier fluid that is immiscible with the sample fluid via the inlet to the microchannel at an input volumetric flow rate (Qn) and removing fluid from the microchannel via the outlet at an output volumetric flow rate (Qout) (paragraph 44 describes how the isolator fluid is provided via second microchannel 120 (as shown in FIG. 3) and is immiscible with the sample fluid);
d) positioning the opening in the sample fluid (FIGs. 2-5 and 7 show the opening in position to take a sample);
e) setting the input volumetric flow rate (Qn) to be smaller than the output volumetric flow rate (Qout), the difference resulting in a take-up volumetric flow rate (Qtakeup) of sample fluid through the opening that results in compartments of sample fluid embedded in the carrier fluid (FIG. 3 shows a situation when sample fluid is aspirated into the device. FIG. 5 shows the system with the sample fluid isolated in a compartment by the isolator fluid. FIG. 7 shows multiple compartments of sample fluid);
e1) identifying positions of the dispersed objects in the sample fluid, including a position of a target object selected from the dispersed objects, by a first sensor unit (FIG. 18, both detector 1830, which uses atomic force microscopy, and objective 1880, which uses optical microscopy, can detect and identify targets dispersed in the sample fluid);
f) changing a position of the opening relative to a target object from a starting relative position to a target position to bring the opening proximate to the target object (paragraph 42 describes a multi-axis staging device to move the device from one target to another. FIG. 6 shows the probe being withdrawn from a first position); and
g) drawing the target object into the microchannel together with a respective compartment of sample fluid when embedding the compartment of sample fluid in the carrier fluid according to step e) (FIG. 7 shows multiple compartments of target objects that have been sampled).
Regarding claim 16, Bernick teaches the system according to claim 2, wherein the system comprises the container (paragraph 42 lists several, including a glass slide, dish, or multi-well plate).
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) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bernick (US patent publication 20140011226) in view of Autebert (US patent 10391488).
Regarding claim 5, Bernick teaches the system according to claim 3, the positioning unit being configured to move the opening at a velocity (vopening) towards the target object (paragraph 42 describes the multi-axis staging device used to move the device. Note that any movement inherently has a velocity).
Bernick does not explicitly teach sampling while moving the probe, so does not explicitly teach that the velocity (vopening) is selected such that the take-up volumetric flow rate (Qtakeup) compensates or substantially compensates for a displacement of sample fluid towards the target object caused by moving the first microfluidic device through the sample fluid.
In the same field of endeavor of microfluidic systems to collect and isolate microscopic objects from fluids, Autebert does teach that the velocity (vopening) is selected such that the take-up volumetric flow rate (Qtakeup) compensates or substantially compensates for a displacement of sample fluid towards the target object caused by moving the first microfluidic device through the sample fluid (FIG. 4 shows the process of moving the collection system while collecting several target objects (2a, 2b, 2c, and 2d). Note that the target objects are not pushed aside by the movement of the microfluidic probe head 3, indicating that the second flow rate Q2 is adequate to compensate for the displacement of the immersion liquid 11 due to the movement of microfluidic probe head 3). As a result of choosing proper flow rates compared to the velocity, Autebert is able to collect and isolate a plurality of target objects along a surface (FIG. 4) without displacing them away from the microfluidic probe head.
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 microfluidic device of Bernick with the mobile sampling of Autebert, performing the routine optimization of flow rates and velocities necessary to ensure the predictable results, like those of Autebert, that the samples may be collected without pushing away the target objects due to displacement of the sample fluid with a reasonable expectation of success.
Claim(s) 13-14 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bernick (US patent publication 20140011226) in view of Schober (US patent publication 20120079895).
Regarding claim 13, Bernick teaches the system according to claim 1,
While Bernick does discuss injecting samples with various substances, such as peptides (paragraph 3) and labels (FIG. 17), Bernick does not explicitly teach that the system comprises a microfluidic deposition device for depositing the one or more target objects at target sites, wherein the deposition device comprises a microchannel with an opening and at least one inlet, wherein a plurality of compartments of sample fluid embedded in a carrier fluid are flown via the inlet to the opening, wherein at least some of the compartments of sample fluid are dispensed through the opening and deposited on a target surface.
In the same field of endeavor of microfluidic sample collection and isolation, Schober does teach that the system comprises a microfluidic deposition device (FIG. 6B, microchannel 01) for depositing the one or more target objects at target sites (FIG. 6B, sample fluid A, shown flowing out of the microchannel 01), wherein the deposition device comprises a microchannel (FIG. 6B, microchannel 01) with an opening and at least one inlet, wherein a plurality of compartments of sample fluid embedded in a carrier fluid are flown via the inlet to the opening, wherein at least some of the compartments of sample fluid are dispensed through the opening (paragraph 36) and deposited on a target surface (FIG. 4, the container that contains each sample). By choosing proper flow conditions, Schober is able to release material from sample compartments without releasing the carrier fluid isolating the sample compartments.
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 microfluid handling system of Bernick with the sample release method of Schober, for example by switching which of reservoirs 136 and 140 acts as fluid source and which acts as fluid receptacle (see FIG. 1 and the final sentence of paragraph 38 of Bernick), with the predictable result of being able to release samples previously collected with a reasonable expectation of success.
Regarding claim 14, Bernick, as modified by Schober, teaches or renders obvious the system according to claim 13,
Bernick further teaches that the system is configured to deliver a support fluid via a manipulation inlet (FIG. 12, third microchannel 1204) into the microchannel to squeeze a compartment of sample fluid located proximate to the opening (FIG. 16 shows third microchannel 1204 squeezing portions of isolator fluid between sample compartments).
Bernick does not teach the deposition device of Bernick, as modified by Schober, described above, so does not explicitly teach that the manipulation inlet and microchannel are of the deposition device or that squeezing the compartment of sample fluid is out of the microchannel of the deposition device through the opening.
In the same field of endeavor of microfluidic sample collection and isolation, Schober does teach that the deposition device (FIG. 6B, microchannel 01) or that squeezing the compartment of sample fluid is out of the microchannel of the deposition device through the opening (FIG. 6B, sample fluid A exiting the microchannel due to greater flow into the microchannel than through the outlet of the microchannel). By choosing proper flow conditions, Schober is able to release material from sample compartments without releasing the carrier fluid isolating the sample compartments.
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 deposition device of the microfluid handling system of Bernick, as modified by Schober, with an additional manipulation inlet (similar to the third microchannel 1204 in FIGs. 12-16 of Bernick) to effectively increase the flow rate V1 into the microchannel, with the predictable result of squeezing sample fluid out of the opening of the deposition device with a reasonable expectation of success.
Regarding claim 18, Bernick, as modified by Schober, teaches or renders obvious the system according to claim 13,
Bernick further teaches that the system comprises a control unit (FIG. 18, system controller 1840), and further comprises a manipulation inlet (FIG. 12, third microchannel 1204), wherein the control unit controls the system to deliver a support fluid via the manipulation inlet into the microchannel at determined time points to squeeze a compartment of sample fluid located proximate to the opening (FIG. 16 shows third microchannel 1204 squeezing portions of isolator fluid between sample compartments).
Bernick does not teach the deposition device of Bernick, as modified by Schober, described above, so does not explicitly teach that the manipulation inlet and microchannel are of the deposition device or that squeezing the compartment of sample fluid is out of the microchannel of the deposition device through the opening.
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 deposition device of the microfluid handling system of Bernick, as modified by Schober, with an additional manipulation inlet (similar to the third microchannel 1204 in FIGs. 12-16 of Bernick) to effectively increase the flow rate V1 into the microchannel, with the predictable result of squeezing sample fluid out of the opening of the deposition device with a reasonable expectation of success.
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bernick (US patent publication 20140011226) in view of Okano (US patent publication 20150231635).
Regarding claim 17, Bernick teaches the system according to claim 1, wherein the system comprises a container forming a support surface, wherein the system is configured to take up the microscopic objects when dispersed across the support surface (paragraph 42, the bottom surface of the inside of a multi-well plate supports the contents, and cells in different locations are dispersed. Intracellular material from different cells, which are dispersed across a surface, is itself dispersed across the surface, particularly the portions supporting those cells. Further, one of ordinary skill in the art would recognize that, while Bernick describes the use of the device in terms of intracellular material, the device is perfectly capable of collecting extracellular samples), wherein the support surface comprises a structure for prearranging the microscopic objects (paragraph 42, the multiple wells of a multi-well plate).
Bernick does not explicitly teach the structure comprising one or more elongated grooves.
In the same field of endeavor of manipulating microscopic objects, such as cells, Okano does teach the structure comprising one or more elongated grooves (FIG. 40, grooves 4003). By including elongated grooves, Okano is able to interconnect adjoining cell culture zones (paragraph 424) used for measuring a human cell while culturing the cell (paragraph 425).
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 multi-well plate of Bernick with the elongated grooves of Okano to enable the interconnection of adjoining cell culture zones, with predictable results and a reasonable expectation of success.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bernick (US patent publication 20140011226) in view of Ismagilov (US patent publication 20110112503).
Regarding claim 19, Bernick teaches the system according to claim 1,
Bernick does not explicitly teach that the system comprises a target surface for depositing the object(s), wherein the target surface comprises areas that are more wettable by the sample fluid than by the carrier fluid.
In the same field of endeavor of microfluidic sampling and deposition of isolated fluid plugs, Ismagilov does teach that the system comprises a target surface for depositing the object(s) (FIG. 7 shows a stimuli plug being deposited onto a substrate), wherein the target surface comprises areas that are more wettable by the sample fluid than by the carrier fluid (paragraph 97 characterizes the substrate as hydrophilic. Note that hydrophilic surfaces are more wettable by aqueous solutions than by oil-based liquids). By using a hydrophilic substrate, Ismagilov is able to study fluids that are water-based (paragraph 58 lists a number of potential sample sources).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have designed the microfluidic device of Bernick using a hydrophilic substrate like that of Ismagilov that is mor wettable by the sample fluid than by the isolator fluid (which are water-based and oil-based, respectively. See paragraph 44 of Bernick) so as to provide a surface which the sample fluid may easily wet, with predictable results and a reasonable expectation of success.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Shojaei-Baghini (non-patent literature “Automated Micropipette Aspiration of Single Cells”) also discloses a microfluidic device that can identify cells in a bulk solution via a specific image recognition algorithm, plan and implement an approach for the collection device to move a collection device to the target microscopic object, and apply suction to the target microscopic in an automated way.
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/PAUL SCHNASE/Examiner, Art Unit 2877
/TARIFUR R CHOWDHURY/Supervisory Patent Examiner, Art Unit 2877
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