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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-32 in the reply filed on 5/5/2026 is acknowledged. The traversal is on the ground(s) that Tokonami does not anticipate the limitations of claim 1. However, the limitations are still obvious based on Tokonami in view of Gieseler and Zborowski (see below for further details). And therefore, the common element does not constitute a special technical feature.
Claim Objections
Claim 1 is objected to because of the following informalities: Line 6 has a period, where it appears a comma is intended. Appropriate correction is required.
Examiner’s Comments – Allowable Subject Matter Disclosed
Applicant can overcome the prior art rejections by amending claim 1 by adding all the following to claim 1 (note that the clarity/112b issues would also still need to be addressed): wherein the dynamic localized heating of the fluid is brought about by a laser or an infrared laser or at least one infrared light emitting diode; wherein the inhomogeneous field of hydrodynamic flows comprises at least one stagnation point and the at least one particle is trapped at least temporarily in the vicinity of the stagnation point; wherein a deviation of an actual position of the at least one particle from the stagnation point is observed and the force acting on the particle is determined in dependence of this deviation; at least one target spatial configuration of the particle(s) in the fluid is defined and wherein the following further steps are carried out:a) an actual spatial configuration of the particle(s) is captured,b) a specific dynamic localized heating event to be applied to the fluid is determined in dependence of at least one recent actual spatial configuration of the particle(s) and a target configuration of the particle(s),c) the specific dynamic localized heating event as determined in step b) is applied at least once to the fluid and d) at least one or all of steps a) to c) are repeated; a cost function is calculated on the basis of a recent actual spatial configuration of the particles and a target configuration of the particles and the specific dynamic localized heating event to be determined in step b) is determined in dependence of the cost function.
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 1-32 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 reads, “determining at least on force acting on the particle(s)…” It’s unclear whether this refers to determining a magnitude of a force, a type of force, or simply whether a force is present. This lack of clarity causes the scope of the claims to be indefinite. For the sake of examination, it will be interpreted as determining either a presence or magnitude of a force.
Claim 16 reads, “…a captured spatial configuration of the particle.” It’s unclear whether this is required to be connected to the claim limitation of the parent claim 1, “Capturing a spatial configuration of the particle…” In other words, it’s unclear what (if any) connection these two limitations have with each other. This lack of clarity causes the scope of the claim to be indefinite. For the sake of examination, it will be interpreted as any captured spatial configuration of the particle.
Regarding claims 25-26 and 29, the term “recently captured spatial configuration” in claim 25 is a relative term which renders the claim indefinite. The term “recently captured spatial configuration” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It’s unclear what time periods of capturing is encompassed by the requiring it to be recent. This lack of clarity causes the scope of the claim to be indefinite. For the sake of examination, it will be interpreted as previously captured. Similar reasoning applies to “recent actual spatial configuration” in claims 26 and 29.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5, 7, 10-11, 17-22, 24-25, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Tokonami (US 20200182770 A1; cited by Applicant) in view of Gieseler (Optical tweezers — from calibration to applications: a tutorial) and Zborowski (US 5974901 A) .
Regarding claim 1, Tokonami teaches a method (figures 1, 11, and 12) comprising:
generating an inhomogeneous field of hydrodynamic flows (paragraph 76) in a fluid (liquid sample in paragraph 76) by specific dynamic localized heating events (paragraphs 76 and 59; 50 heats as explained in paragraph 59; this is done dynamically because a laser actively heats which causes the sample to move through convection; for locally, see paragraph 85),
spatially manipulating the particle by the hydrodynamic flows (paragraphs 76 and 85-86),
capturing a spatial configuration of the particle(s) within the fluid (paragraph 89, 90, 50, and 74; figure 12)
determining at least one force acting on the particle(s) (gravity in paragraph 42) and evaluating the captured spatial configuration of the particle(s) (paragraph 89, 90, 50, and 74; figure 12).
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Tokonami doesn’t explicitly teach the determining is by the evaluating.
However, it is conventional to determine a force by evaluating captured spatial configurations. For example, like Tokonami (and like the instant application), Gieseler is concerned with spatially manipulating particles and with spatially manipulating particles within a fluid and teaches capturing a spatial configuration of the particle(s) within the fluid, and determining at least one force acting on the particle(s) by evaluating the captured spatial configuration of the particle(s) (pages 100-106 and 131). Additionally, Gieseler teaches this provides the benefit of being applicable to a wide range of forces pages 100-106 and 131). Similarly, like Tokonami (and like the instant application and like Gieseler), Zborowski is concerned with imaging particles within a field and teaches capturing a spatial configuration of the particle(s) within the fluid, and determining at least one force acting on the particle(s) by evaluating the captured spatial configuration of the particle(s) (column 5, lines 5-25 and column 9, lines 25-50). Additionally, Zborowski teaches this provides the benefit of determining particle characteristics from the determined forces (column 9, lines 35-50).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Tokonami such that the method comprises determining at least one force acting on the particle(s) by evaluating the captured spatial configuration of the particle(s) in order to determine particle characteristics from the forces acting on the particle as well as to identify the effects of external forces such as gravity on the movement of the particles, while using techniques applicable to a wide range of forces.
Regarding claim 2, Tokonami teaches the field of hydrodynamic flows decreases in the direction of the field (figure 11, in the horizontal direction, from the edges to the center).
Regarding claim 3, Tokonami teaches the fluid is or contains water (paragraph 70).
Regarding claim 4, Tokonami teaches the particle(s) to be manipulated is (are) at least one of the following: a biological particle, a cell, a virus, a tissue fragment, a metal particle, a composite material particle, a polymer particle, a nanoparticle, a spherical bead, a magnetic bead, a tethering molecule, a cellular organelle, a phase-separated droplet that itself is containing protein, RNA, or other biomolecules (paragraph 70).
Regarding claim 5, Tokonami teaches the dynamic localized heating of the fluid is brought about by a laser or an infrared laser or at least one infrared light emitting diode (paragraphs 76-77).
Regarding claim 7, Tokonami teaches a determination of a specific dynamic localized heating event to be applied to the fluid comprises the determination of at least one of:" 2-dimensional scan path in the fluid, " 3-dimensional scan path in the fluid," laser intensity," laser scanning speed," scanning frequency of the laser, or " number of times the scanning path is scanned (intensity corresponds to power as explained in paragraph 59; paragraphs 99-102).
Regarding claim 10, Tokonami teaches the spatial manipulation of the particle(s) comprises at least one of:" pushing or moving specified particle(s) towards specified target locations in the fluid," moving specified particle(s) along specified paths in the fluid," keeping specified particle(s) in specified target locations in the fluid," keeping specified particle(s) in specified target orientations in the fluid, or " pushing or moving specified particle(s) towards specified target orientation(s) in the fluid (figure 11; paragraphs 76 and 83-86).
Regarding claim 11, Tokonami teaches the capturing of the actual spatial configuration of the particle(s) comprises at least one of the following:" a 1-dimensional position of the particle(s), " a 2-dimensional position of the particle(s), " a 3-dimensional position of the particle(s)," a measurement of an orientation of the particle(s) within a plane, or " a measurement of a 3-dimensional orientation of the particle(s) in space (paragraph 89, 90, 50, and 74; figure 12).
Regarding claim 17, in the above combination at least one external force is applied to the particle (gravity in paragraph 42 of Tokonami; also see the forces of the honeycomb on the particles in Tokonami; also see gravitational, electric, and magnetic in Zborowski in column 5, lines 15-25 and the forces in Gieseler pages 100-106 and 131).
Regarding claim 18, in the above combination the external force is at least one of:" a magnetic force; " an electrostatic force; " a gravitational force; " a force generated by an optical trap; or " a force exerted by a tethered molecule (gravity in paragraph 42 of Tokonami; also see the forces of the honeycomb on the particles in Tokonami; also see gravitational, electric, and magnetic in Zborowski in column 5, lines 15-25 and the forces in Gieseler pages 100-106 and 131).
Regarding claim 19, in the above combination the external force is time-dependent or constant for at least a specified period of time (all the forces described with respect to claim 17 are either time dependent or constant).
Regarding claim 20, in the above combination the force acting on the particle is calibrated by comparison to the external force (Gieseler, page 104).
Regarding claim 21, in the above combination the force acting on the particle is determined by evaluation of a statistical distribution (suggested by averages and standard deviations in Zborowski, column 9 as well as the PSD of the particle position in Geiseler pages 100-106) of the lateral positions of the particle in the vicinity of a stagnation point and a temperature of the fluid (suggested by pages 2-6 of Weinhert, which explains the imaging and fluid dynamics depend on the temperature, as well as the particle positions which is used to determine the forces).
Regarding claim 22, Tokonami teaches at least two particles are simultaneously spatially manipulated (paragraphs 76 and 85-86; figure 11) and/or that forces acting on at least two particles are simultaneously determined.
Regarding claim 24, Tokonami teaches the fluid contains particles (paragraphs 76 and 85-86; figure 11) which enable a capturing of the field of hydrodynamic flows.
Regarding claim 25, Weinhert teaches the specific localized heating events are determined in dependence of at least one of:a recently captured spatial configuration of the particle(s), or a recently captured field of hydrodynamic flows (paragraphs 74-75 and figure 9).
Regarding claim 31, Tokonami doesn’t explicitly teach future dynamic localized heating events to be applied to the fluid are calculated using machine learning.
Official Notice is taken that it is well known in the art of measuring and testing to use machine learning.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that future dynamic localized heating events to be applied to the fluid are calculated using machine learning in order to save the user’s time and effort in determining the details of future of implementations of the method.
Claims 6, 8, 26-28, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Tokonami, Gieseler, and Zborowski as applied to claims 5 and 1 above, and further in view of Kreysing (US 20200379235 A1).
Regarding claim 6, Tokonami doesn’t explicitly teach the dynamic localized heating events of the fluid are brought about by repetitive scanning of a focal volume of the laser along a path in the fluid.
However, Tokonami teaches scanning the relative position of the sample and objective, and therefore the focal volume of the laser (paragraph 45). Additionally, like the above combination (and like the instant application), Kreysing is also concerned with manipulating fluid flow with a laser providing heating and with spatially manipulating particles in a fluid flow and teaches dynamic localized heating events of the fluid are brought about by repetitive scanning of a focal volume of the laser along a path in the fluid (paragraphs 59, 69, and 76).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the dynamic localized heating events of the fluid are brought about by repetitive scanning of a focal volume of the laser along a path in the fluid in order to ensure that all the particles in the fluid have moved as desired.
Regarding claim 8, in the above combination, the paths along which the laser is scanned is chosen such that the heating radiation does not hit the particle(s) to be manipulated (Kreysing: paragraphs 59, 69, and 76).
Regarding claim 26, in the above combination at least one target spatial configuration of the particle(s) in the fluid is defined and wherein the following further steps are carried out:a) an actual spatial configuration of the particle(s) is captured,b) a specific dynamic localized heating event to be applied to the fluid is determined in dependence of at least one recent actual spatial configuration of the particle(s) and a target configuration of the particle(s),c) the specific dynamic localized heating event as determined in step b) is applied at least once to the fluid (pargraphs 74-76 of Tokonami) and d) at least one or all of steps a) to c) are repeated (since the laser irradiates multiple positions, it is repeating the heating).
Regarding claim 27, in the above combination the target spatial configuration of the particle(s) in the fluid comprises at least one of: specified target location(s) of the particle(s) in the fluid (Tokonami, paragraphs 73-76; figures 1 and 11).
Regarding claim 28, in the above combination the target spatial configuration of the particle(s) in the fluid is " a 1-dimensional localization of the particle(s)," a 2-dimensional localization of the particle(s) or " a 3-dimensional localization of the particle(s) (Tokonami, paragraphs 73-76; figures 1 and 11).
Regarding claim 30, Tokonami doesn’t explicitly teach the following data are stored in a database:" previous actual spatial configurations of the particle(s)," previous dynamic localized heating events applied to the fluid determined on the basis of at least a respective actual spatial configuration and a target configuration and " changes in the actual spatial configurations of the particle(s) caused by the respective dynamic localized heating event applied to the fluid,and wherein future dynamic localized heating events to be applied to the fluid are calculated using at least parts of the data stored in the database.
Official Notice is taken that it is well known in the art to have a database containing previous measurements and to have future measurements utilize at least parts of the data stored in the database.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the following data are stored in a database:" previous actual spatial configurations of the particle(s)," previous dynamic localized heating events applied to the fluid determined on the basis of at least a respective actual spatial configuration and a target configuration and " changes in the actual spatial configurations of the particle(s) caused by the respective dynamic localized heating event applied to the fluid,and wherein future dynamic localized heating events to be applied to the fluid are calculated using at least parts of the data stored in the database – in order to have future measurements be more efficient by learning from how the system and method worked previously.
Claims 1, 5-6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Weinhert (Optically driven fluid flow along arbitrary microscale patterns using thermoviscous expansion; cited by Applicant) in view of Gieseler and Zborowski.
Regarding claim 1, Weinhert teaches a method comprising:
generating an inhomogeneous field of hydrodynamic flows in a fluid by specific dynamic localized heating events (page 2),
spatially manipulating the particle by the hydrodynamic flows (pages 2 and 6),
capturing a spatial configuration of the particle(s) within the fluid (page 2).
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Weinhert doesn’t explicitly teach determining at least one force acting on the particle(s) by evaluating the captured spatial configuration of the particle(s).
However, Weinhert teaches determining velocity and position of the particle(s) by evaluating the captured spatial configuration of the particle(s) (pages 2 and 6). And it’s conventional to determine force from velocity and position (see the prior art of record). Additionally, Gieseler is concerned with spatially manipulating particles and with spatially manipulating particles within a fluid and teaches capturing a spatial configuration of the particle(s) within the fluid, and determining at least one force acting on the particle(s) by evaluating the captured spatial configuration of the particle(s) (pages 100-106 and 131). Additionally, Gieseler teaches this provides the benefit of being applicable to a wide range of forces pages 100-106 and 131). Similarly Zborowski is concerned with imaging particles within a field and teaches capturing a spatial configuration of the particle(s) within the fluid, and determining at least one force acting on the particle(s) by evaluating the captured spatial configuration of the particle(s) (column 5, lines 5-25 and column 9, lines 25-50). Additionally, Zborowski teaches this provides the benefit of determining particle characteristics from the determined forces (column 9, lines 35-50).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Weinhert such that the method comprises determining at least one force acting on the particle(s) by evaluating the captured spatial configuration of the particle(s) in order to determine particle characteristics from the forces acting on the particle as well as to identify the effects of external forces such as gravity on the movement of the particles, while using techniques applicable to a wide range of forces.
Regarding claim 5, Weinhert teaches the dynamic localized heating of the fluid is brought about by a laser or an infrared laser or at least one infrared light emitting diode (pages 2 and 6).
Regarding claim 6, Weinhert teaches the dynamic localized heating events of the fluid are brought about by repetitive scanning of a focal volume of the laser along a path in the fluid (abstract, pages 2, 4).
Regarding claim 9, the above combination doesn’t explicitly teach a scan rate of the repetitive scanning is chosen such that temperature fields in the sample can relax between successive scans.
However, Weinher teaches the relaxation time is 0.1 ms (page 5).
Additionally, Official Notice is taken that it is well known in the art of optical measurements and testing (and more generally in scientific inquiry) to repeat measurements.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that a scan rate of the repetitive scanning is chosen such that temperature fields in the sample can relax between successive scans in order to repeat the measurement and test with similar initial temperature conditions, in order for the new measurement to not be unduly influenced by the temperature variations created by the previous measurement.
Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Weinhert, Gieseler, and Zborowski as applied to claim 1 above, and further in view of Tanyeri (Hydrodynamic trap for single particles and cells; cited by Applicant).
Regarding claim 12, Weinhert doesn’t explicitly teach the inhomogeneous field of hydrodynamic flows comprises at least one stagnation point and the at least one particle is trapped at least temporarily in the vicinity of the stagnation point.
Like the above combination (and like the instant application), Tanyeri is directed to spatially manipulating particles in fluid flows and teaches the inhomogeneous field of hydrodynamic flows comprises at least one stagnation point and the at least one particle is trapped at least temporarily in the vicinity of the stagnation point (figure 1). Additionally, Tanyeri teaches that this provides the benefit of providing high resolution manipulation of particles (page 1).
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It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the inhomogeneous field of hydrodynamic flows comprises at least one stagnation point and the at least one particle is trapped at least temporarily in the vicinity of the stagnation point in order to provide high resolution manipulation of particles.
Regarding claim 13, in the above combination a deviation of an actual position of the at least one particle from the stagnation point is observed and the force acting on the particle is determined in dependence of this deviation (Tanyeri, page 2).
Regarding claim 14, in the above combination the inhomogeneous field of hydrodynamic flows comprising at least one stagnation point is generated by at least two hydrodynamic flows directed in opposite directions toward the stagnation point (Tanyeri, figure 1).
Claims 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Weinhert, Gieseler, and Zborowski as applied to claim 1 above, and further in view of Chang (WO 2007046871 A2).
Regarding claim 15, Weinhert doesn’t explicitly teach the at least two hydrodynamic flows directed in opposite directions are rotated in a plane around the stagnation point.
Like Weinhert (and like the instant application), Chang is directed to spatially manipulating particles in fluids and provides a general teaching of rotating a plane around the stagnation point (paragraph 26)
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the at least two hydrodynamic flows directed in opposite directions are rotated in a plane around the stagnation point in order to provide additional degrees of freedom for controlling the motion of the particles (e.g. see Chang, paragraphs 26-29).
Regarding claim 16, in the above combination an azimuthal direction in which the at least two hydrodynamic flows directed in opposite directions are applied is chosen in dependence of a captured spatial configuration of the particle (implicit since one must know enough about the spatial configuration of the particles ahead of time, even if the capturing is merely acquiring a mental model of the particles being in the spatial position delineated by the fluid).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Weinhert, Gieseler, and Zborowski as applied to claim 1 above, and further in view of Wang (US 20120288925 A1).
Regarding claim 23, Weinhert doesn’t explicitly teach for at least one particle, a torque acting on the respective particle is determined.
Like Weinhert (and like the instant application), Wang is directed to spatially manipulating particles and provides a general teaching for at least one particle, a torque acting on the respective particle is determined (paragraphs 15 and 56).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above method by also determining torque on at least on particle such that for at least one particle, a torque acting on the respective particle is determined in order to provide a full characterization of the dynamics of the particle.
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Tokonami, Gieseler, Zborowski, and Kreysing as applied to claim 26 above, and further in view of Tirapu Azpiroz (US 20170286583 A1).
Regarding claim 29, Tokonami doesn’t explicitly teach a cost function is calculated on the basis of a recent actual spatial configuration of the particles and a target configuration of the particles and the specific dynamic localized heating event to be determined in step b) is determined in dependence of the cost function.
However, the above combination comprises Tirapu Azpiroz is also concerned with spatially manipulating particles in a fluid and provides a general teaching of using cost functions that are calculated on the basis of recent spatial configuration of particles and a desired configuration of particles and having the future events to be determined be determined in dependence of the cost function (abstract; paragraphs 58-62).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that a cost function is calculated on the basis of a recent actual spatial configuration of the particles and a target configuration of the particles and the specific dynamic localized heating event to be determined in step b) is determined in dependence of the cost function – in order to optimize the positioning of the particles by taking into consideration the desired positioning and the previously measured positioning in order to optimize the spatial manipulation so that the positioning is within the desired thresholds.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Weinhert, Gieseler, and Zborowski as applied to claim 1 above, and further in view of Tanyeri and Bustamante (US 20160027545 A1).
Regarding claim 32, Weinhert teaches the particle to be manipulated and analysed is a molecule (pages 2 and 8-9).
Winhert doesn’t explicitly teach a flow field having at least two stagnation points is generated within the fluid, and at least two portions of the tethered molecule are held in the stagnation points by the hydrodynamic fluids.
Like the above combination (and like the instant application), Tanyeri is directed to spatially manipulating particles in fluid flows and teaches the inhomogeneous field of hydrodynamic flows comprises at least one stagnation point and the at least one particle is trapped at least temporarily in the vicinity of the stagnation point (figure 1). Additionally, Tanyeri teaches that this provides the benefit of providing high resolution manipulation of particles (page 1).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the inhomogeneous field of hydrodynamic flows comprises at least one stagnation point and the at least one particle is trapped at least temporarily in the vicinity of the stagnation point in order to provide high resolution manipulation of particles.
The above combination doesn’t explicitly teach the molecule is a tethered molecule (Wienhert doesn’t use the exact phrase “tethered molecule,” and it’s not immediately clear to the examiner whether the molecules and biomolecules of Weinhert are tethered molecules).
Like the above combination (and like the instant application), Bustamante is directed to spatial manipulation of particles and teaches the particle is a tethered molecule (paragraphs 9 and 33).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the above combination such that the molecule is a tethered molecule in order to be able to control and analyze a wide variety of particles, including tethered molecules.
Additional Prior Art
WO 2009147961 A1 (cited by Applicant) Reads, “FIG. 5 is a time-series diagram of the amount of displacement of the cell membrane and the acting force on the cell membrane during compression, which is obtained according to the present invention and is targeted to a yeast cell. The positional relationship between the microdevice and the cell at each time indicated by the dotted line is shown. The yeast cells are suspended in Milli-Q water supplemented with 1 wt% BSA, a 5 m counter-wall is formed in front of the microdevice, and the yeast cells are sandwiched between the counterwall and the microdevice. We succeeded in measuring the reaction force in real time while compressing cells at 0.5 Hz cycle. Thus, the position of the microdevice and the cell reaction force were continuously measured, and the images showed that the yeast cells were deformed by a maximum of 0.0 9 9 ^ m.
Conclusion
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/RUFUS L PHILLIPS/ Examiner, Art Unit 2877
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