DETAILED ACTION
Response to Arguments
Applicant's arguments filed 22 June 2026 have been fully considered but they are not persuasive.
It is noted, that prior art cannot teach the claimed invention as a triangle with sides equal to the height does not exist. Therefore, the claims are rejected under 112(a) and 112(b) as discussed herein below.
For the purposes of examination, it is interpreted that by equal the claim means close enough to achieve high resolution, which as discussed on page 4 of the last office action is suggested by the prior art.
Additionally, it is noted that a body etched therein, is a product by process limitation. MPEP 2113 recites “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
Here, the claimed product is not materially different from the product of the prior art, therefore etched channels and opening is not seen as different from the channels in the body of the prior art.
Lastly, in both Van Berkle and Fang discussed previously and shown below have a triangle with an apex opposite an opening within the body. Note there is no requirement that the body form an apex, only that “a triangle within the body comprises an apex”. As clearly seen in figure 11, the triangle is imaginary. Therefore the apex is not required to be structurally formed by the body. Therefore, even though Van Berkel appears to have a body with a flat surface, an triangle can be formed within the body as indicated in the annotated drawing below (see pages 9-10). Additionally, Fang clearly shows the body forming an apex and a triangle within the body as indicated in the annotated figure 6 below (see page 17).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, 6-7, 10-11, 14, 16-17 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 fails to meet the written description requirement for reciting “the body further comprising an opening, wherein a width of the primary channel, a width of the spray channel and a width of the opening for a triangle within the body comprising an apex within the body, which apex is opposite the opening, and a height of the triangle is equal to the width of each of the primary channels.”
Specifically, MPEP 2163 (I)(B) recites:
“the written description requirement prevents an applicant from claiming subject matter that was not adequately described in the specification as filed. New or amended claims which introduce elements or limitations that are not supported by the as-filed disclosure violate the written description requirement. See, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971)” (emphasis added).
Here, the paragraph bridging pages 11-12 of the originally filed specification recites:
“In preferred embodiments for producing maximum signal, the height of the triangle abc shown in FIG. 11 is near to or approximately equal to the width of the channels. For example, in FIG. 11, the width 1003 of the solvent channel and the width of the spray channel are 30 μm and the height 1005 of the triangle abc is 30 μm. This design provided the best mass spectra in terms of the SIN ratio.”
That is, the instant specification suggests a height about equal to the width of the channels. However, there is no disclosure that within the body there can exist a triangle with widths equal to the height of the triangle.
Specifically, as understood by basic geometry, a triangle with two sides of equal length would be an isosceles triangle (see Math.net submitted herewith defining an isosceles triangle). Half of an isosceles triangle is a right triangle. See image below
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In basic trigonometry, in order for a hypotenuse to be the same height as a line from the apex to the base, the angle of the triangle would need to be a right angle (i.e. a rectangle instead of a triangle).
In the instant figure 7 shows a similar geometry to above in mathnet. (see annotated figure 11 below)
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Therefore, while there is support for a triangle with a width of the channels to be about the height from the apex (about being understood in context of spatial resolution, see page 4 of the non-final rejection of 07 January 2026), the specification does not adequately support possession of a triangle having two sides of equal length (i.e. widths of channels) and a height of equal to the lengths of the sides. That is, if they did it would no longer be a triangle, but rather a rectangle.
Independent claim 14 requires commensurate limitations lacking written description as discussed above.
All dependent claims fail to meet the written description requirement by virtue of their dependencies on respective independent claims 1 and 14.
Claims 1, 3-4, 6-7, 10-11, 14, 16-17 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 1 and 14 fail to meet the enablement requirement for requiring “the body further comprising an opening, wherein a width of the primary channel, a width of the spray channel and a width of the opening for a triangle within the body comprising an apex within the body, which apex is opposite the opening, and a height of the triangle is equal to the width of each of the primary channels.”
As discussed above, a triangle could not be formed with two sides having equal to a height, because one of ordinary skill in the art would recognize that such a triangle does not exist. Therefore, one of ordinary skill in the art could not make and use the claimed invention, as one of ordinary skill in the art would not understand a triangle to have two sides of equal length to the height.
All dependent claims are non-enabling by virtue of their dependencies on rejected claims 1 and 14.
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, 3-4, 6-7, 10-11, 14, 16-17 and 19 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.
Claims 1 and 14 are vague and indefinite for reciting “the body further comprising an opening, wherein a width of the primary channel, a width of the spray channel and a width of the opening for a triangle within the body comprising an apex within the body, which apex is opposite the opening, and a height of the triangle is equal to the width of each of the primary channels”. Specifically, it is not clear how the height of a triangle can be equal to the width of each channel (see discussion above).
All dependent claims are vague and indefinite by virtue of their dependencies on rejected claims 1 and 14.
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.
Claims 1 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Van Berkel (USPN 9,064,680) in view of Timperman (US pgPub 2006/0285999) ) and further in view of Laskin et al. (US pgPub 2018/0033597) in view of Gratz et al. (DE4040786) as evidenced by Javid (submitted with the office action of 21 June 2024).
Regarding claim 1, Van Berkel teaches a system for ionizing a sample (various embodiments seen in figures. Col. 2, lines 43-56 teach a system for analyzing samples), the system comprising:
a probe (probe, see abstract) comprising a body (body 154 of probe 150 seen in figures 4a-4b) that has etched therein (note product by process, see discussion above) a primary channel (solvent delivery conduit fig. 4b, 166 for example, wherein the sample conduit is arranged on probe at different positions throughout figures) and a spray channel (liquid extraction channel, for example 174 in figure 4b) intersecting at a fixed orientation in the body (174/166 are in the body 154 as seen in figure 4a-1b) relative to each other (as seen in figure 4b, different orientations seen in other figures), the body further comprising at an opening (170 of 154)
wherein a width of the primary channel, a width of the spray channel, and a width of the opening form a triangle within the body comprising an apex within the body, which apex is opposite the opening and a height of the triangle is equal (interpreted as about as there is no support the height to be equal to the width) to the width of each of the primary channel, and the spray channel (see annotated figures below);
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and
wherein the probe is operable to create a liquid bridge at the opening between the primary channel, the spray channel, and a surface that comprises a sample (78, liquid micro junction is equivalent to the bridge, see col. 4, lines 33-38) when the opening is located proximal to the surface that comprises the sample (as seen in figure 2 for instance) and a liquid is flowed through the primary channel into the spray channel across the opening (col. 4, lines 33-38); and
a nanospray emitter (fig. 2b, 86, note col. 6, lines 31-48 teach reducing the channel dimensions of each succeeding flow channel, the electrospray emitter channel is reduced from the dimensions of the nip channel which are reduced from the liquid extraction channel and the channels having a width of 10-1000nm, thus the electrospray emitter has a nano-dimensioned width and therefore interpreted as a nanospray emitter (i.e. nm is size and emitting a spray)) in fluid communication with the opening via the spray channel (as seen in figure 2b) a point between the opening and the nanospray emitter (anywhere along 74 which starts at claimed opening and ends at emitter 86)
wherein the primary channel and the spray channel are integrally formed within the body of the probe (as seen in figure 2b, probe comprises primary channel 66 and spray channel 74, thus integrally formed)
Berkel fails to disclose wherein the probe further comprises a makeup solvent channel in fluid communication with the spray channel.
However, Timperman teaches wherein the probe further comprises a makeup solvent channel in fluid communication with the spray channel (fig. 1, make-up flow channel in communication with main channel 25 which extends from reservoir 15 (i.e. opening) to a spray capillary 29).
Timperman modifies Van Berkel by suggesting a make-up flow channel attached to the main channel of an electrospray ionization device.
Since both inventions are directed towards flowing samples to an electrospray ionization device, it would have been obvious to one of ordinary skill in the art to attach a make-up flow channel to the liquid extraction channel 74 of Van Berkel (i.e. equivalent to the main channel of Timperman because it extends from a sample inlet to an ESI emitter tip) because the make-up solution adjusts the flow rate to the ESI tip to optimize flow rate and stability of the electrospray ([0049] and [0052] of Timperman).
The combined device fails to disclose one or more shear force detection sensors integrated into the body of the probe that allow for maintaining a desired distance between the primary channel and the spray channel and the surface.
However, Laskin et al. teach one or more shear force detection sensors (fig. 1, 48b, paragraph [0045] discloses a piezoelectric device as the sensor 48b, thus a shear force detection sensor as disclosed in the instant specification) integrated into the body of the probe (48b integrated into probe body 40) that generates data that is processed by a controller that then provides for maintaining a desired distance between the primary channel and the spray channel and the surface ([0052] teaches vibratory variation detected with sensor 48b is a measure of shear force variation with distance separating probe tip from surface, paragraph [0053] teaches output of lock-in amplifier 114 corresponds to the vibratory response level of sensor 48b, paragraph [0054] teaches output of lock-in amplifier 114 is conditioned by signal conditioning circuitry 116, the resulting digital signal is applied to controller logic 82 to determine the relative separation distance between probe tip and sample face. Paragraph [0055] teaches controller 80 including logic 82 maintains an approximately constant separation distance between tip and uneven surface 100 of the sample) ) wherein the one or more shear force detection sensors are one or more piezoelectric devices proximate a tip of the probe (sensor 48b is proximate the tip relative to sensor 48a, paragraph [0048] teaches “stimulator 48a being located farther away from tip 43 than sensor 48b”).
Laskin modifies the combined device by teaching a means to maintain a constant separation distance between the tip and an uneven surface.
Since both inventions are directed towards combined topography and mass spectrometry of a sample, it would have been obvious to one of ordinary skill in the art to incorporate the sensing and agitator features of Laskin on the combined because it would allow for the capture of detailed 3D information about a sample and its composition even for uneven surfaces ([0004] and [0058]).
While Laskin suggests a mechanical fixing of the piezoelectric device to the probe, the combined device fails to identify they type of piezoelectric device used, thus fails to disclose the piezoelectric device is a piezoelectric disc and the piezoelectric device is integrally formed within the body of the probe.
However, Gratz et al. teach measuring with a piezoelectric disk (see page 5, last sentence of first paragraph) and the piezoelectric device is integrally formed within the body of the probe (see page 5, last sentence of first paragraph teaches piezoelectric disk built into the probe base body).
Gratz et al. modifies the combined device in view of Laskin by suggesting the type of piezoelectric device to use as a sensor.
Since both inventions are directed towards measuring with a probe, it would have been obvious to select the piezoelectric disk as discussed in Gratz et al. as the type of piezo in Laskin because it would resolve the problem of which type of piezoelectric to use. That is, the piezoelectric disk is suitable for the intended purpose of Laskin. Lastly, as evidenced by Javid, piezoelectric discs in probes offer a cost effective alternative (see abstract and page 14, section 2.2.3). Moreover, building the disk into the probe base body would resolve how the piezo device of the combined device is mechanically fixed to the probe.
Regarding claim 10, Van Berkel teaches wherein the spray channel is from about 1 micron in cross-sectional width (col. 6, lines 43-45 teaches 1000 nm thus 1 micron).
Regarding claim 11, Van Berkel teaches wherein the opening is from 1 micron to about 600 microns wide (col. 6, lines 43-45, since each channel can be 1 micron and the channels intersect as shown in the annotated figure above, the opening larger than 1 micron).
Claims 1, 3-4, 6, 7, 14, 16-17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Yang (US pgPub 2016/0168617) in view of (a) Van Berkel or (b) Fang (US pgPub 2021/0325351) and further in view of Campbell or Timperman and further in view of Laskin et al. (US pgPub 2018/0033597) (note: in this interpretation, claim 2 is interpreted to be the same sensor as the sensor of claim 1 (i.e. “a sensor” in claim 2 is “a shear force detection sensor” of claim 1 as apparent from the instant specification)) in view of Gratz et al. as evidenced by Javid.
Regarding claim 1, Yang teaches a system (fig. 4 or fig. 26a and [0106]) for ionizing a sample, the system comprising:
a probe (440) comprising a primary channel (solvent supplying groove 446 (channel when binding 2 silicon wafers)) and a spray channel (sampling groove 444 to nanoESI emitter 454) intersecting at a fixed orientation relative to each other at an opening in a tip of the probe (444 and 446 intersect as seen in figure 26b. Formed by bound silicon wafers thus in a fixed orientation), wherein the probe is operable to create a liquid bridge at the opening between the primary channel, the spray channel ([0106] openings 450 and 454 are in fluid communication via groove 444, thus a liquid bridge required between 446 and 444), and a surface that comprises a sample ([0051] teaching conventional nano-DESI recites “ a solvent (e.g., a methanol/water solution) is supplied through one capillary. The solvent dissolves the analytes on a small spot of the sample surface at the junction of the tips of the two capillaries. The solution containing the dissolved analytes is then collected at the tip of the second capillary and is transported through the second capillary to a narrowed orifice at an emitter end where the solution is ionized into charged droplets at an inlet of a mass spectrometer in a similar way of a conventional nano-spray ionization source”. Paragraph [0052] teaches the novel disclosed single probe where the two capillaries have been integrated into an integral unit. Thus various embodiments including 26a show the same process disclosed in fig. 1 and associated text) when the opening is located proximal to the surface that comprises the sample ([0051]) and a liquid is flowed through the primary channel into the spray channel across the opening ([0051]); and
a nanospray emitter in fluid communication with the opening via the spray channel (454 in figure 26a is in communication with 450 via 444, see nanospray emitter in figure e26a and not paragraphs [0052]-[0053] as discussed above. Further note there are various embodiments disclosed by Yang that read on the claimed invention. Figure 26a is used as the example) a point between the opening and the nanospray emitter (anywhere along sampling groove 444 which starts at claimed opening and ends at emitter “Nano-ESI emitter”, see figure 26a)
wherein the primary channel and the spray channel are integrally formed within the body of the probe (as seen in figure 4 or 26a, probe comprises primary channel 446 and spray channel 44, thus integrally formed).
While Yang teaches a concave or scooped tip which may enable the liquid junction to be more stably sustained resulting in better sampling stability (see figure 26(b) and paragraph [0107]), Yang fails to expressly teach wherein a width of the primary channel, a width of the spray channel, and a width of the opening form a triangle and a height of the triangle is about equal to the width of each of the primary channel, and the spray channel.
However, Van Berkle teaches the claimed body as discussed above and wherein a width of the primary channel, a width of the spray channel, and a width of the opening form a triangle within the body comprising an apex within the body, which apex is opposite the opening and a height of the triangle is equal (interpreted as about as there is no support the height to be equal to the width) to the width of each of the primary channel, and the spray channel (see annotated figures below);
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Van Berkel modifies Yang by suggesting the shape of the channels with respect to the tip.
Since both inventions are directed towards establishing a liquid bridge, it would have been obvious to one of ordinary skill to the art before the effective filing date to adopt the geometry suggested in Van Berkel in the device of Yang because it would resolve the problem as to how to arrange the channels with respect to the tip to establish a liquid bridge.
Alternatively, Fang teaches a body with channels and an opening forming a triangle within the body (see annotated figure below, wherein the etching is a product by process, therefore is not sufficient to distinguish the claimed invention over Fang) teaches wherein a width of the primary channel, a width of the spray channel, and a width of the opening form a triangle comprising an apex and a height of the triangle is equal (as above interpreting equal to be about, note paragraph [0103] teaches fig. 6 has a higher signal than conventional techniques thus about equal as understood by the instant specification (see page 4 of the non-final rejection of 07 January 2026)) to the width of each of the primary channel, and the spray channel and wherein the apex is opposite the opening (see annotated figure below and paragraph [0110]).
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Fang modifies Yang by suggesting the position of the channels with respect to liquid bridge.
Since both inventions are directed towards maintaining a stable MS signal, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to place the channels of Yang in the orientation suggested by Fang because it would predictably maintain the stable MS signal as desired by Yang. Moreover, integrating the channels into a single probe would reduce the cost of manufacture ([0005]) and simply the system of Yang to achieve a fixed geometry ([0088]).
Yang has the same deficiencies as Van Berkel above. However, when modified in the same way by Campbell or Timperman results in the claimed invention. See above for teaching of the make-up channel in each reference and rational to combine.
The combined device fails to disclose one or more shear force detection sensors integrated into a body of the probe that allow for maintaining a desired distance between the primary channel and the spray channel and the surface.
However, Laskin et al. teach one or more shear force detection sensors (fig. 1, 48b, paragraph [0045] discloses a piezoelectric device as the sensor 48b, thus a shear force detection sensor as disclosed in the instant specification) integrated into a body of the probe (48b integrated into probe body 40) that generates data that is processed by a controller that then provides for maintaining a desired distance between the primary channel and the spray channel and the surface ([0052] teaches vibratory variation detected with sensor 48b is a measure of shear force variation with distance separating probe tip from surface, paragraph [0053] teaches output of lock-in amplifier 114 corresponds to the vibratory response level of sensor 48b, paragraph [0054] teaches output of lock-in amplifier 114 is conditioned by signal conditioning circuitry 116, the resulting digital signal is applied to controller logic 82 to determine the relative separation distance between probe tip and sample face. Paragraph [0055] teaches controller 80 including logic 82 maintains an approximately constant separation distance between tip and uneven surface 100 of the sample) ) wherein the one or more shear force detection sensors are one or more piezoelectric devices proximate a tip of the probe (sensor 48b is proximate the tip relative to sensor 48a, paragraph [0048] teaches “stimulator 48a being located farther away from tip 43 than sensor 48b”).
Laskin modifies the combined device by teaching a means to maintain a constant separation distance between the tip and an uneven surface.
Laskin modifies Yang by providing a sensor and actuator to the primary channel.
Since both inventions are directed towards nano-DESI, it would have been obvious to one of ordinary skill in the art to incorporate the sensing and agitator features of Laskin on the device of Yang because in addition to mass analysis the sensor and agitator allow for 3D shape of the sample surface.
While Laskin suggests a mechanical fixing of the piezoelectric device to the probe, the combined device fails to identify they type of piezoelectric device used, thus fails to disclose the piezoelectric device is a piezoelectric disc and the piezoelectric device is integrally formed within the body of the probe.
However, Gratz et al. teach measuring with a piezoelectric disk (see page 5, last sentence of first paragraph) and the piezoelectric device is integrally formed within the body of the probe (see page 5, last sentence of first paragraph teaches piezoelectric disk built into the probe base body).
Gratz et al. modifies the combined device in view of Laskin by suggesting the type of piezoelectric device to use as a sensor and building the sensor into the body of the probe.
Since both inventions are directed towards measuring with a probe, it would have been obvious to select the piezoelectric disk as discussed in Gratz et al. as the type of piezo in Laskin because it would resolve the problem of which type of piezoelectric disk to use. That is, the piezoelectric disk is suitable for the intended purpose of Laskin. Lastly, as evidenced by Javid, piezoelectric discs in probes offer a cost effective alternative (see abstract and page 14, section 2.2.3). Moreover, building the disk into the probe base body would resolve how the piezo device of the combined device is mechanically fixed to the probe.
Regarding claims 3 and 16, Yang in view of Laskin teach a sensor (fig. 1, 48b) and an agitator (fig. 3, 48a, [0045] of Laskin) operable to move the tip of the probe perpendicularly relative to the surface (Laskin, [0052]) as the probe translates across the surface (Laskin, fig. 6 occurs for a x, y position and at the end of routine, figure 6 returns to figure 5 for next position ([0056]), thus agitating as probe translates across the surface (i.e. translate a coordinate perform height determination routine, advance to next position), moreover the xyz states seen in figure 1 would allow for agitation as the probe translates); and a computer (80) comprising a non-transitory tangible memory (82a) and a processor (82) in communication with the sensor (48a) and the agitator (48) and operable to control the agitator based on a signal received from the sensor ([0052] “oscillator 112 provides a time-varying single, the frequency of which is set by the controller…The response detected with sensor 48b varies with distance D between a probe tip 46a and uneven surface” paragraph [0053] comparison of oscillator single with sensed signal, paragraph [0055] teaches the conditional test for changing height between sample, thus the processor 82 (which performs the steps of figure 6) controls the agitator by moving the sample stage height based on a signal form the sensor).
Regarding claims 4 and 17, Yang in view of Laskin teach a lock-in amplifier (fig. 3, 114) in in communication with the computer (since 114 is part of 80, and in communication with processor 82 it is in communication with the computer. Moreover, figure 9 shows an embodiment where 114 is in communication with computer 680 with the functionality of figures 1-6 see paragraph [0061]); the computer operable to detect vibration of the tip and move the tip relative to the sample to maintain a desired amplitude of tip vibrations. ([0052]-[0055] teaches 114 provides a way to compare AC oscillator signal with detected signal, paragraph [0054] teaches output of 114 to 116 applied to control logic 82 to determine separation and paragraph [0055] teaches logic 82 maintains approximately constant separation between tip and uneven surface by adjusting the stage. Since a difference in resonant vibration amplitude occurs when the distance between probe tip 46a and surface 100 changes ([0052]) and the computer controls the height of the stage in response, the controller detects vibrations (via receiving input from 114) and moves the stage such that the tip relative the sample maintains a desired amplitude of vibration).
Regarding claim 6, Yang teaches an electrode ([0051] teaches inlet of a mass spectrometer. A mass spectrometer inherently has electrodes, one of the electrodes is interpreted to be the claimed electrode) operably coupled to the probe (via inlet see paragraph [0051]); and an ion analysis device that comprises a mass analyzer ([0051] and [0066]); wherein the system is configured such that the probe is at atmospheric pressure ([0005] note ambient desorption/ionization techniques), the mass analyzer is under vacuum (mass analyzers inherently operate under vacuum in order to reduce the change of ions colliding with other molecules), and the nanospray emitter points in a direction of an inlet of the ion analysis device such that ions expelled from the tip of the probe are received to the inlet of the ion analysis device (as seen in figures 4, 13, 15,16).
Regarding claim 7, Yang teaches solvent delivery device (fig. 4, 108) that is operably coupled to the probe such that solvent from the solvent delivery device is supplied to the tip of the probe via the primary channel (via plunging the syringe, solvent is supplied to 106).
Claim 14 is commensurate in scope with claim 1 and thus taught as discussed in the citations above. In addition Yang teaches contacting the sample with the probe ([0066] note “the sharp tip can be inserted into a single cell”, [0068] “single-probe was inserted into cells”) applying a voltage to the probe ([0069] teaches sample ionization a the nanospray emitter end of the probe, therefore inherently requiring a voltage), thereby generating ions of the analyte at the nanospray emitter ([0069]); and transferring the ions into a mass spectrometer to thereby analyze the ion ([0051]).
Regarding claim 19, Yang in view of Laskin teach plotting a series of analyte data obtained from the mass analyzer by location of the opening relative to the sample during desorption of the analyte to create an image of analyte distribution in the sample (Laskin, 0060, opening between probe 40 and 50 in figure 2. For each of the regions, causing one or more corresponding regional sample analytes to be extracted in response to the fluid agent ([0032])).
Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Van Berkel, Campbell, Laskin1 in view of Gratz et al. as evidenced by Javid and further in view of Kitamura et al. (USPN 5,939,715)
Regarding claim 3, the combined device fails to disclose a sensor and an agitator operable to move the tip of the probe perpendicularly relative to the surface as the probe translates across the surface; and a computer comprising a non-transitory tangible memory and a processor in communication with the sensor and the agitator and operable to control the agitator based on a signal received from the sensor.
However, Kitamura et al. teach a sensor (fig. 3, 7) and an agitator (16) operable to move the tip of the probe perpendicularly relative to the surface (col. 1, lines 60-63 teach piezo vibrating the cantilever and col. 2, lines 8-18 teach feedback loop to correct distance between tip and sample) as the probe translates across the surface (col. 2, lines 21-23); and a computer (controller 14) comprising a non-transitory tangible memory and a processor (inherent to create a topographic image and display, col. 2, lines 19-23) in communication with the sensor and the agitator and operable to control the agitator based on a signal received from the sensor (fig. 3 shows 14 in communication with scan driver 13 to control the agitator by adjustment in the z direction based on the signal received from error amplifier which receives information from detector 7).
Kitamura modifies Van Berkel by teaching the measurement and vibration in an AFM.
Since both inventions are directed towards AFMs, it would have been obvious to use the method of correcting distances of Kitamura et al. in the device of Van Berkel because it would resolve how to perform the topographic imaging via AFM.
Regarding claim 4, Van Berkel in view of Kitamura et al. teach a lock-in amplifier (Kitamura et al, fig. 3m 9) in in communication with the computer (with control device 14 via error amp 10); the computer operable to detect vibration of the tip and move the tip relative to the sample to maintain a desired amplitude of tip vibrations (col. 2, lines 8-18).
Relevant art:
Datwani (US pgPub 2019/0157061). teaches a system for analyzing a sample (fig. 1a and 1b), the system comprising: a probe (fig. 1, 51) comprising a primary channel (59) and a spray channel (61) intersecting at a fixed orientation relative to each other at an opening in a tip (fig. 1a, 59 opening at bottom of probe 51).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J LOGIE whose telephone number is (571)270-1616. The examiner can normally be reached M-F: 7:00AM-3:00PM.
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/MICHAEL J LOGIE/Primary Examiner, Art Unit 2881
1 note: in this interpretation, claim 2 is interpreted to be a different sensor than the sensor of claim 1
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