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 .
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.
Claim(s) 1-14 and 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Marshall (US 20180059005 A1) in view of Edwards (US 20070016333 A1).
Regarding Claim 1: Marshall discloses a system to measure a liquid analyte and a prescribed reference solution in a transmission cell (Fig. 1), the system comprising:
a liquid flow cell (12) having a sample chamber with a chamber window (22) configured to alternately receive the liquid analyte and the prescribed reference solution (S and R shown alternating in figure; [0020]);
a tunable optical source (16) configured to emit coherent light across a range of wavelengths ([0020]: “tunable QCL laser”), the tunable optical source configured to transmit the coherent light through the chamber window to produce a chamber signal (24);
a detector having an optical range to detect the chamber signal, the detector configured to detect the chamber signal (20);
Marshall teaches flow-control and measurement of flow rate in [0164], [0225], and [0228], but does not teach a flow sensor configured to measure a flow rate and a flow direction of the liquid analyte and the prescribed reference solution through the output of the liquid flow cell.
However, Edwards teaches a flow control arrangement wherein a flow sensor configured to measure a flow rate and a flow direction of a liquid through the output of the liquid flow cell (Fig. 1).
It would have been obvious to someone of ordinary skill in the art to have incorporated the flow meter of Edwards into the system of Marshall. One would be motivated to make such a modification on the basis of monitoring and maintaining a desired fluid flow.
Regarding Claim 2: Marshall in view of Edwards discloses Marshall in view of Edwards discloses the system of claim 1, but both fail to explicitly teach wherein the flow sensor measures the flow rate a sampling rate between 10 Hz and 100 kHz.
Edwards teaches measuring fluid flow and using the flow rate as feedback for controlling the control valve. Sampling rate is a result-effective variable that affects the resulting measurement and control performance. Therefore, it would have been obvious to someone of ordinary skill in the art to have selected an appropriate sample rate as a matter of routine optimization. See MPEP 2144.
Regarding Claim 3: Marshall in view of Edwards discloses Marshall in view of Edwards discloses the system of claim 1, wherein the flow sensor is configured to measure flow rate:
in a forward direction of the fluid flow (Edwards: Fig. 13; [0069]: “A flow meter block 230 monitors the downstream flow output and provides this feedback to the controller block 225.”);
in a reverse direction of the fluid flow; or
in both a forward direction and reverse direction of the fluid flow.
Regarding Claim 4: Marshall in view of Edwards discloses Marshall in view of Edwards discloses the system of claim 1, wherein the measured flow rate is used to determine a volume of fluid that flows through the liquid flow cell (Edwards, [0059]: “A pressure signal representing a pressure differential across an orifice may be used with the cross-sectional area of the orifice, the cross-sectional area of the inlet and outlet portions just before and after the orifice, and the density of the fluid to determine the volumetric flow rate.”).
Regarding Claim 5: Marshall in view of Edwards discloses Marshall in view of Edwards discloses the system of claim 1, wherein the measured flow rate is determined as a function of time to provide diagnostic information about the alternately receiving the liquid analyte and the prescribed reference solution at the liquid flow cell (Edwards: Figs. 15a-15d).
Regarding Claim 6: Marshall in view of Edwards discloses Marshall in view of Edwards discloses the system of claim 1 further comprising:
a controller in electrical communication with the system (Marshall: Fig. 1, controller 29) configured to:
fully automate the alternatively receiving the liquid analyte and the reference solution (Marshall, [0078]: “[0078] Such a system may be entirely automated and programmable through computer control, allowing for sample analysis under a large number of conditions rapidly and with automation.”);
fully automate the detection of the chamber signal of the liquid analyte spectrum and the reference solution spectrum (Marshall, [0078]); and
fully automate the measurement of the flow rate of the liquid analyte and the flow rate of the prescribed reference solution (Marshall, [0078]).
Regarding Claim 7: Marshall in view of Edwards discloses the system of claim 6, but fails to explicitly teach wherein the controller is configured to compare measured flow rate of the liquid analyte to the measured flow rate of the prescribed reference solution to give diagnostic information about the alternately receiving the liquid analyte and the prescribed reference solution at the liquid flow cell.
Marshall teaches an analyzer looking at the difference in fluids as a function of dwell time in [0076] (“the analyzer may be operated to look at the difference in fluids in the interrogation region as a function of the difference in dwell times between the two channels. In this manner the analyzer functions as fluidic comparator.”). Marshall also discloses a feedback loop to control fluid velocity in [0063]. Further, Marshall provides motivation to maintain similar flow rates between the two channels to reduce measurement error in [0211] (“in a flowing modulated system such as MMS, different flow rates between the two channels may induce a temperature difference between the reference and sample fluid streams which would lead to measurement error.”).
Therefore, it would have been obvious to someone of ordinary skill in the art to have compared the flow rates of the liquid analyte and prescribed reference solution to give diagnostic information about the alternately receiving the liquid analyte and prescribed reference solution at the liquid flow cell. One would need information comparing the flow rates between the two channels for the feedback loop to adjust the flow rates such that they are the same. One would be motivated to do son on the basis of reducing measurement error.
Regarding Claim 8: Marshall in view of Edwards discloses the system of claim 7, wherein the diagnostic information indicates that a flow rate of the liquid analyte or a flow rate of the prescribed reference solution should be increased or decreased (reasons provided for claim 7 and Edwards, [0015]: “The processor may also be configured to compare the calculated fluid flow to a desired fluid flow and adjust the position of the variable orifice to increase or decrease fluid flow as required.”)
Regarding Claim 9: Marshall in view of Edwards discloses the system of claim 8, wherein the controller is configured to automatically:
determine the measured flow rate as a function of time of the liquid analyte and the prescribed reference solution; and
compare the measured flow rate of the liquid analyte to the measured flow rate of the prescribed reference solution (Marshall, [0078]: “[0078] Such a system may be entirely automated and programmable through computer control, allowing for sample analysis under a large number of conditions rapidly and with automation.”; Edwards, [0015]: “The processor may also be configured to compare the calculated fluid flow to a desired fluid flow and adjust the position of the variable orifice to increase or decrease fluid flow as required”).
Regarding Claim 10: Marshall in view of Edwards discloses the system of claim 9, but fails to teach wherein the controller is configured to automatically increase or decrease a gas pressure forcing the one or both of the liquid analyte or the prescribed reference solution from a well plates based on the comparison of the measured flow rate of the liquid analyte to the measured flow rate of the prescribed reference solution.
Marshall teaches an entirely automated system in [0078] (“[0078] Such a system may be entirely automated and programmable through computer control, allowing for sample analysis under a large number of conditions rapidly and with automation.”), gas flow through the channels in [0165] (“A channel fluid offset measurement with a common fluid (or a gas) in both channels (e.g. the reference fluid is commonly used) may be used to measure and compensate for such channel to channel differences.”), and the use of a well plate in [0071] (“In conventional chemical denaturation studies the sample containing an analyte (e.g. protein) and chemical denaturant concentration is varied discretely in sample containers, such as the well containers in a standard 96 well plate.”). Lastly, Edwards, teaches increasing or decreasing pressure to achieve a desired flow rate in [0015] (“The processor may also be configured to compare the calculated fluid flow to a desired fluid flow and adjust the position of the variable orifice to increase or decrease fluid flow as required.”).
Therefore, it would have been obvious to someone of ordinary skill in the art to have modified Marshall in view of Edwards to automatically increase or decrease a gas pressure forcing the one or both of the liquid analyte or the prescribed reference solution from a well plate based on the comparison of the measured flow rate of the liquid analyte to the measured flow rate of the prescribed reference solution as a matter of predictably providing automated regulation of the relative flow rates of the two fluids.
Regarding Claim 11: Marshall discloses a method to measure a liquid analyte in a prescribed reference solution, comprising:
alternately flowing the liquid analyte and the prescribed reference solution through a fluid chamber in a liquid flow cell (Fig. 1, S and R alternating);
emitting an infra-red (IR) light from an IR light source, the IR light being filtered through an optical filter ([0020]: “A Mid-IR source 16, such as a fixed frequency or tunable QCL laser 16 as shown”; [0213]: “A series of neutral density filters, a continuously variable filter such as a polarizing filter, or controlling the laser drive current directly may be deployed.”);
transmitting the filtered IR light through a sample cell in the fluid chamber to produce a chamber signal (24); and
using a detector having an optical range to detect the chamber signal (20).
Marshall fails to explicitly teach a liquid analyte with a weak absorbance in a prescribed reference solution with a very high absorbance. However, Marshall discloses an absorbance differential between the two ([0021]: “the laser frequency (or equivalently, wavelength) is set to a value where the sample fluid has a differential absorbance relative to the reference fluid”). Therefore, it would have been obvious to someone of ordinary skill in the art to have set the laser frequency to a value where the sample fluid has a weak absorbance and the prescribed reference solution has a very high absorbance.
Marshall also fails to teach measuring a flow rate of an output of the liquid flow cell with a flow meter positioned in-line along tubing carrying the output of the liquid flow cell.
However, Marshall teaches flow-control and measurement of flow rate in [0164], [0225], and [0228].
Edwards also teaches a flow control arrangement wherein a flow sensor configured to measure a flow rate and a flow direction of a liquid through the output of the liquid flow cell (Fig. 1).
It would have been obvious to someone of ordinary skill in the art to have incorporated the flow meter of Edwards into the system of Marshall and measure a flow rate of an output of the liquid flow cell with a flow meter positioned in-line along tubing carrying the output of the liquid flow cell. One would be motivated to make such a modification on the basis of monitoring and maintaining a desired fluid flow.
Regarding Claim 12: Marshall in view of Edwards discloses the method of claim 11, wherein a flow rate versus time curve is determined for the liquid analyte and the prescribed reference solution (Edwards: Fig 2a).
Regarding Claim 13: Marshall in view of Edwards discloses the method of claim 12, wherein the flow rate versus time curves determined for the liquid analyte and the prescribed reference solution provides diagnostic information about the alternately flowing the liquid analyte and the prescribed reference solution through a fluid chamber in a liquid flow cell (Edwards: Fig. 2a).
Regarding Claim 14: Marshall in view of Edwards discloses the method of claim 13, wherein:
the flow rate versus time curves are automatically determined for the liquid analyte and the prescribed reference solution (Marshall, [0078]: “Such a system may be entirely automated and programmable through computer control, allowing for sample analysis under a large number of conditions rapidly and with automation.”); and
the diagnostic information to control a gas pressure forcing the one or both of the liquid analyte or the prescribed reference solution from the well plates is automatically provided (Marshall, [0063]: “…a feedback loop or calibration loop may be used to control the fluidic modulation rate or a pressure reduced to control fluid velocity in the interrogation region.”).
Regarding Claim 18: Marshall discloses a method to measure a liquid analyte with a weak absorbance in a prescribed reference solution with a very high absorbance, the method comprising:
alternately flowing the liquid analyte and the prescribed reference solution through a fluid chamber in a liquid flow cell to a waste fluid exit line (Fig. 1, S and R alternating);
emitting an infra-red (IR) light from an IR light source, the IR light being filtered through an optical filter ([0020]: “A Mid-IR source 16, such as a fixed frequency or tunable QCL laser 16 as shown”; [0213]: “A series of neutral density filters, a continuously variable filter such as a polarizing filter, or controlling the laser drive current directly may be deployed.”);
transmitting the filtered IR light through a sample cell in the fluid chamber to produce a chamber signal (24);
using a detector having an optical range to detect the chamber signal (20); and
Marshall fails to explicitly teach a liquid analyte with a weak absorbance in a prescribed reference solution with a very high absorbance. However, Marshall discloses an absorbance differential between the two ([0021]: “the laser frequency (or equivalently, wavelength) is set to a value where the sample fluid has a differential absorbance relative to the reference fluid”). Therefore, it would have been obvious to someone of ordinary skill in the art to have set the laser frequency to a value where the sample fluid has a weak absorbance and the prescribed reference solution has a very high absorbance.
Marshall also fails to explicitly teach measuring a flow rate and a flow direction of the waste fluid analyte and prescribed reference solution with a flow meter positioned in the waste fluid exit line.
However, Marshall teaches flow-control and measurement of flow rate in [0164], [0225], and [0228].
Edwards also teaches a flow control arrangement wherein a flow sensor configured to measure a flow rate and a flow direction of a liquid through the output of the liquid flow cell (Fig. 1).
It would have been obvious to someone of ordinary skill in the art to have incorporated the flow meter of Edwards into the system of Marshall and measure a flow rate of an output of the liquid flow cell with a flow meter positioned in-line along tubing carrying the output of the liquid flow cell. One would be motivated to make such a modification on the basis of monitoring and maintaining a desired fluid flow.
Regarding Claim 19: Marshall in view of Edwards discloses the method of claim 18, but both fail to teach further comprising:
flowing the waste liquid analyte and the waste prescribed reference solution through a 3-way valve positioned between the flow meter and the waste fluid connector.
However, it would have been obvious to include a 3-way valve to selectively direct the waste analyte and waste reference to a waste outlet. Marshall teaches separate channels for an analyte and a reference solution that would need to be removed from the system after use. A 3-way valve is a known, common element for routing fluids and connecting inlet paths to a common outlet. Using such a valve would allow the waste analyte and waste reference to be selectively routed through the same waste path, simplifying the fluid system. One would be motivated to include such a valve as a matter of combining known elements according to their known functions to yield the predictable result of selectively directing either waste stream to the waste outlet. See MPEP 2143.
Claim(s) 15-17 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Marshall in view of Edwards, in further view of Perkins (US 10906038 B2).
Regarding Claim 15: Marshall in view of Edwards discloses the method of claim 11 but fails to teach further comprising:
reverse-flow priming and flushing the fluid chamber in the liquid flow cell with a system water or a system buffer.
Perkins teaches a reverse direction fluid flow to flush dead volume from a sample container into a waste reservoir (Col. 37, lines 62-67: “the denature, purge and/or space fluids are pulled from fluid reservoirs (such as bottles, bags, and the like) and are passed in the reverse direction through the injector and sampling nozzle disposing into the now empty sample container, such as sample well, or into a separate container or well designated for waste.”).
Marshall and Perkins both address fluid systems with residual fluid occupying a sample-delivery path. Therefore, it would have been obvious to someone of ordinary skill in the art to have modified the combination of Marshall and Edwards to provide the reverse-flow priming and flushing disclosed in Perkins. One would be motivated to make such a modification to clear the residual fluid from the sample-delivery path and prevent future sample interference by employing a known reverse-flow flushing technique.
Regarding Claim 16: Marshall in view of Edwards, in further view of Perkins discloses the method of claim 15, but all fail to explicitly teach wherein the flow meter determines a flow rate and a flow direction of the system water and the system buffer.
However, it would have been obvious to someone of ordinary skill in the art to monitor the flow of the buffer as a predictable use of a known technique for monitoring fluid flow, as taught by Edwards. One would be motivated to do so on the basis of verifying the buffer flow rate with the flow meter performing its expected function in the buffer’s path, which is the same as the sample delivery path.
Regarding Claim 17: Marshall in view of Edwards, in further view of Perkins discloses the method of claim 15, wherein the reverse-flow priming and flushing the fluid chamber in the liquid flow cell effectively removes dead volume in sample delivery paths (Perkins: Col. 37, lines 62-67: “the denature, purge and/or space fluids are pulled from fluid reservoirs (such as bottles, bags, and the like) and are passed in the reverse direction through the injector and sampling nozzle disposing into the now empty sample container, such as sample well, or into a separate container or well designated for waste.”).
Regarding Claim 20: Marshall in view of Edwards discloses the method of claim 18, but both fail to teach further comprising:
reverse-flow priming and flushing the fluid chamber in the liquid flow cell through the 3-way valve attached to and in liquid communication with system water and system buffer.
Perkins teaches a reverse direction fluid flow to flush dead volume from a sample container into a waste reservoir (Col. 37, lines 62-67: “the denature, purge and/or space fluids are pulled from fluid reservoirs (such as bottles, bags, and the like) and are passed in the reverse direction through the injector and sampling nozzle disposing into the now empty sample container, such as sample well, or into a separate container or well designated for waste.”).
Marshall and Perkins both address fluid systems with residual fluid occupying a sample-delivery path. Therefore, it would have been obvious to someone of ordinary skill in the art to have modified the combination of Marshall and Edwards to provide the reverse-flow priming and flushing disclosed in Perkins. One would be motivated to make such a modification to clear the residual fluid from the sample-delivery path and prevent future sample interference by employing a known reverse-flow flushing technique.
Conclusion
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/MIYA DOWNING/Examiner, Art Unit 2884
/DAVID J MAKIYA/Supervisory Patent Examiner, Art Unit 2884
