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 .
Priority
Applicant’s claim for the benefit of a prior-filed application (has PRO 62260944, filed on 30 November 2015; has PRO 62338074, filed on 18 May 2016; CON of 15363908, filed on 29 November 2016; CON of 16688141, filed on 19 November 2019; CON of 16983293, filed on 03 August 2020) under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS. —Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 41 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 41 does not further limit the subject matter of Claim 34 because Claim 34 already requires “a transparent portion … configured to allow for imaging of the mobilized analyte mixture,” such that Claim 41’s limitation “the transparent portion is configured to allow imaging of the mobilization” merely restates the imaging requirement already recited in Claim 34.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102 / § 103
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.
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:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 34-49 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over ZHENG et al. (“Microfabricated Devices for Capillary Electrophoresis-Electrospray Mass Spectrometry” Analytical Chemistry. 71. 1999. Hereinafter ZHENG).
Regarding Claim 34-35, ZHENG discloses a microfluidic device configured for electrophoretic separation and electrospray mass spectrometry (ABSTRACT; Pg. 3258, Col. 1).
The microfluidic device of Figure 2 includes etched channels for sample, buffer, and gas flow formed in a single glass substrate, and a glass cover plate with drilled wells thermally bonded to the substrate. The device comprises a separation channel (i.e., a first fluid channel), an auxiliary fluid channel (i.e., a second fluid channel) intersecting the separation channel, and two gas channels flanking the outlet. The electrospray exit port is formed by cutting the chip using a dicing saw, and the sheath gas is supplied from a nitrogen gas tank with rubber O rings sealing the gas sheath channel inlet (EXPERIMENTAL SECTION, § B. Microdevice with the Integrated Nebulizer; Pg. 3260, Col. 1).
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Figure 2 of ZHENG et al.
The microfluidic device is formed in a glass substrate with a thermally bonded glass cover plate, and Figure 2 illustrates the channels and wells as visible features of the glass chip. This glass construction provides a transparent portion through which the channel region can be optically imaged (In re Schreiber, 128 F.3d 1473, 1997).
During MS interfacing, the interface uses the pumping action at the mass spectrometer sampling orifice to lower the pressure in the enclosed electrospray region, creating a pressure drop that initiates flow of the analyzed liquid through the electrospray needle and eliminates the need for an external pump (RESULTS AND DISCUSSION, § Microdevice with External Transfer Capillary, Pg. 3261, Col. 1). This pressure drop initiates flow through the microdevice fluid path to the electrospray exit port, which mobilizes liquid in the separation channel toward the orifice (In re Schreiber, 128 F.3d 1473, 1997).
Two gas channels in a V-shape arrangement merge at the electrospray exit port and deliver nitrogen gas to induce suction and dispersion of the auxiliary liquid at the electrospray exit port, and the gas flow aids evaporation of the electrosprayed droplets (RESULTS AND DISCUSSION, § Microdevice with an Integrated Nebulizer, Pg. 3262, Col. 2).
Regarding Claims 36, 37, and 40, ZHENG discloses a microfluidic device of Claim 35. Figure 2 of ZHENG illustrates that a BGE well is in fluid communication with the separation channel, and Figure 3 further illustrates that the BGE well is electrically connected to a high voltage power supply (§ Microdevice with External Transfer Capillary; Pg. 3261). Based on the disclosed hardware by ZHENG, it would have been obvious to a person having ordinary skill in the art to apply a first electrical field using the high voltage power supply to effect isoelectric focusing, and to subsequently apply a second electrical field using the high voltage power supply to effect mobilization.
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Figure 3 of ZHENG et al.
Regarding Claims 38, 39, and 41, ZHENG discloses a microfluidic device of Claim 37. Figure 2 of ZHENG illustrates that the device is formed entirely from glass, which inherently allows imaging of the analyte mixture during separation, focusing, or mobilization (In re Schreiber, 128 F.3d 1473, 1997).
Regarding Claim 42, ZHENG discloses a microfluidic device of Claim 34. ZHENG discloses that the auxiliary liquid reservoir contains myoglobin solution in methanol, water with acetic acid (i.e., an electrolyte), and that the high voltage power supply is connected through an electrode inserted into the auxiliary liquid reservoir (Pg. 3263, Col. 1).
Regarding Claims 43-46, ZHENG discloses a microfluidic device of Claim 34. Figure 2 of ZHENG illustrates that the separation channel and the auxiliary liquid channel intersect at a confluence region downstream of the separation channel (i.e., the first fluid channel) and in fluid communication with the auxiliary liquid channel (i.e., the second fluid channel), and the confluence region is in line with the separation channel and the electrospray exit (i.e., the orifice; § B. Microdevice with the Integrated Nebulizer; Pg. 3260, Col. 1).
Regarding Claim 47, ZHENG discloses a microfluidic device of Claim 40. ZHENG discloses that the interface uses the mass spectrometer sampling orifice to initiate flow of the analyzed liquid through the electrospray needle (§ Microdevice with External Transfer Capillary; Pg. 3261, Col. 1).
Regarding Claim 48, ZHENG discloses a microfluidic device of Claim 47. ZHENG discloses that two gas channels in a V shape arrangement merge at the electrospray exit port and deliver nitrogen gas to induce suction and dispersion of the auxiliary liquid at the electrospray exit port, and the gas flow aids evaporation of the electrosprayed droplets, which facilitates electrospray ionization (§ Microdevice with an Integrated Nebulizer; Pg. 3262, Col. 2).
Regarding Claim 49, ZHENG discloses a microfluidic device of Claim 35. ZHENG discloses an internal pressure differential source, where the mass spectrometer sampling orifice lowers pressure in the enclosed electrospray region and creates a pressure drop that initiates flow through the device fluid path (§ Microdevice with External Transfer Capillary; Pg. 3261, Col. 1).
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over ZHENG as applied to claim 49 above, and further in view of XUE et al. (Multichannel Microchip Electrospray Mass Spectrometry, 1997, hereinafter XUE).
Regarding Claim 50, ZHENG discloses a microfluidic device of Claim 49. However, ZHENG does not explicitly disclose the pressure source as a pressure pump.
Using a syringe pump to provide pressure driven flow in comparable microfluidic electrophoresis and electrospray interfacing devices is well known, and ZHENG acknowledges prior experiments using an external syringe pump to generate flow rates in the 100 nL/min range (Pg. 3260, Col. 2).
In this context, XUE discloses a multichannel glass microchip interfaced to an electrospray ionization mass spectrometer (Abstract, Pg. 426). A syringe pump is connected to a well to deliver sample through the channel, and the buffer reservoirs are made airtight to ensure the sample solution flows through only the appropriate channel (Pg. 427, Col. 2). A pressure pump connected to the well necessarily applies pressure to drive flow through the device fluid path, including the first fluid channel.
Stable electrospray required sufficient liquid flow at the channel outlet, and when the electric field alone did not provide bulk flow, a syringe pump was used to deliver the flow necessary for stable electrospray (RESULTS AND DISCUSSION, § Off-Line Microchip Electrospray Studies; Pg. 428).
A person skilled in the art would select a pressure pump, such as the syringe pump used to provide bulk flow for stable electrospray, to apply pressure in ZHENG’s microfluidic device to initiate and control mobilization of liquid toward the electrospray exit, which is a routine flow control choice in comparable microfluidic electrospray interfacing systems.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate a pressure pump, as disclosed by XUE, into the microfluidic device by ZHENG.
Response to Arguments
Applicant’s arguments filed October 28, 2025 have been fully considered but they are not persuasive. The previous rejection under 35 U.S.C. §§ 102 and 103 is maintained and updated for Claims 34–49 in view of ZHENG, and Claim 50 is rejected under 35 U.S.C. § 103 in view of ZHENG and XUE. Applicant’s arguments are addressed by the rejection. Additionally, Applicant is advised to note the newly added rejection under 35 U.S.C. § 112(d).
Conclusion
THIS ACTION IS MADE FINAL. 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 TAK L. CHIU whose telephone number is (703)756-1059. The examiner can normally be reached M-F: 9:00am - 6:00pm (CST).
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/TAK L. CHIU/Examiner, Art Unit 1777
/KRISHNAN S MENON/Primary Examiner, Art Unit 1777