Office Action 6: Notice of Allowance (2025-02-21)

CLAIMS:
AMENDMENTS TO THE CLAIMS

The following listing of claims replaces all prior versions and listings of claims in the instant application.

1-20. (Canceled)219

21\. (Currently Amended) An apparatus, comprising:
a flow cell;
a plurality of reservoirs fluidically coupled to the flow cell, the plurality of reservoirs configured to respectively hold four different nucleotide species;
a sensor operably coupled to the flow cell, the sensor being configured to sense one or more signals produced from incorporations of a nucleotide species of the four different nucleotide species into a plurality of template polynucleotide strands in the flow cell; and
a fluidics controller operably coupled to the plurality of reservoirs, the fluidics controller configured to individually control flow from the plurality of reservoirs to provide a series of nucleotide flows to the flow cell, wherein the series of nucleotide flows comprises a plurality of sequential repetitions of the four different nucleotide species flowed in a predetermined order, wherein in each sequential repetition, each of thefour different nucleotide species is flowed once in the predetermined order,
wherein the series of nucleotide flows further comprises a nucleotide flow sequence included within the plurality of sequential repetitions of the four different nucleotide species, the nucleotide flow sequence meeting predefined criteria such that the nucleotide flow sequence includes:
each of the four different nucleotide species,
no consecutively repeated nucleotide flow of any of the four different nucleotide species, and
a flow ordering such that three different nucleotide species of the four different nucleotide species are flowed before a fourth nucleotide species of the four different nucleotide species is flowed, and such that one or more of the three different nucleotide species is flowed at least twice before the fourth different nucleotide species is flowed,
wherein the series of nucleotide flows includes one or more consecutive repeats of the nucleotide flow sequence, wherein the flow ordering comprises a same number of nucleotide flows for each of the four different nucleotide species,

wherein the nucleotide flow sequence reduces dephasing effects that occurred during previous sequential repetitions of the four different nucleotide species applied to the plurality of template polynucleotide strands in the flow cell.

22\. (Previously Presented) The apparatus of claim 21, wherein the flow cell comprises a plurality of reaction sites, the plurality of reaction sites comprising a reaction site associated with the polynucleotide.

23\. (Previously Presented) The apparatus of claim 22, wherein the plurality of reaction sites comprise a plurality of microwells.

24\. (Currently Amended) The apparatus of claim 22, wherein the apparatus comprises a plurality of sensors, the plurality of sensors comprising the sensor, the plurality of sensors aligned with the plurality of reaction sites, and each sensor of the plurality of sensors configured to sense one or more signals produced from incorporation of the nucleotide species at a corresponding reaction site.

25\. (Previously Presented) The apparatus of claim 21, wherein the sensor is configured to sense pH.

26\. (Previously Presented) The apparatus of claim 21, wherein the sensor comprises a field effect transistor (FET).

27\. (Previously Presented) The apparatus of claim 21, wherein the sensor is configured to sense one or more signals produced from incorporation each of the four different nucleotide species into the polynucleotide.

28\. (Previously Presented) The apparatus of claim 21, wherein the apparatus comprises a plurality of sensors, the plurality of sensors comprising the sensor, each sensor of the plurality configured to sense one or more signals produced from incorporation of the nucleotide species.

29\. (Previously Presented) The apparatus of claim 21, wherein the sensor is one of a plurality of sensors of a sensor array, and the apparatus further comprises a semiconductor substrate, the semiconductor substrate comprising the sensor array.

30\. (Previously Presented) The apparatus of claim 21, further comprising a reference electrode operatively coupled to the sensor.

31\. (Previously Presented) The apparatus of claim 21, wherein the polynucleotide is coupled to a support.

32\. (Previously Presented) The apparatus of claim 31, wherein the support comprises a bead in the flow cell.

33\. (Previously Presented) The apparatus of claim 31, wherein the support is operatively coupled to the sensor.

34\. (Previously Presented) The apparatus of claim 21, further comprising a valve block fluidically coupling the plurality of reservoirs and the flow cell, the fluidic controller operably coupled to control the valve block.

35\. (Previously Presented) The apparatus of claim 21, wherein two or more of the three different nucleotide species are flowed at least twice before the fourth different nucleotide species is flowed in the nucleotide flow sequence.

36\. (Previously Presented) The apparatus of claim 21, wherein all three of the three different nucleotide species are flowed at least twice before the fourth different nucleotide species is flowed in the nucleotide flow sequence.

37\. (Previously Presented) The apparatus of claim 21, wherein one or more of the three different nucleotide species are flowed at least three times before the fourth different nucleotide species is flowed in the nucleotide flow sequence.

38\. (Previously Presented) The apparatus of claim 21, wherein a first and second different nucleotide species of the three different nucleotide species are flowed at least twice and a third nucleotide species of the three different nucleotide species occurs at least three times before the fourth different nucleotide species is flowed in the nucleotide flow sequence.

39\. (Previously Presented) The apparatus of claim 21, wherein two or more of the three different nucleotide species are flowed at least three times before the fourth different nucleotide species is flowed in the nucleotide flow sequence.40.-50. (Canceled)

OFFICE ACTION:
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 .
Application Status
This action is written in response to applicant’s correspondence received on 01/17/2025.  Claims 21-39 are pending. Claims 21 and 24 have been amended. Claims 1-20 and 40-50 have been cancelled.  All pending claims are currently under examination.
Any rejection or objection not reiterated herein has been overcome by amendment.
Withdrawn Claim Rejection – 35 USC 112(b)
The Applicant’s amendments to claim 21 render the claim definite.  The 112(b) rejection is therefore withdrawn.
Withdrawn – Double Patenting Rejection
The Applicant and owner of patent US 9,605,308 has submitted a terminal disclaimer along with the present application.  Thus, the double patenting rejection on the grounds of US 9,605,308 are hereby withdrawn.
Reasons for Allowance
Claims 21-39 are allowed.  With regards to claim 21, the only remaining outstanding rejections were the above-mentioned 112(b) and Double Patenting rejections.  The Applicant has amended claim 21 rendering the claim definite.  Furthermore, the Applicant has filed a terminal disclaimer with their existing patent US 9,605,308, the subject matter and claims of which are substantially similar to the present invention.
With regards to the prior art, as discussed in previous office actions (e.g., the Final action mailed 05/03/2024), apparatus for sequencing and dispensing nucleotides were known, as taught by Rothberg (US 2009/0127589).  Additionally, sequencing strategies with alternative nucleotide flow orderings, where such alternative flow orderings reduce dephasing effects, are also known as taught by Garcia (Garcia et al. Gene. 253:249-257, 2000, supplied with Final Office action mailed 05/03/2024, see 103 rejection of this action for discussion on obviousness).  However, the flow orderings of Garcia were based on alternative flow dispensations created using an anticipated sequence of the nucleotide to be sequenced.  The present apparatus, as recited, relies on successive, sequential flows of predetermined nucleotides interspersed with a flow ordering to reduce dephasing effects (see claim 21).  Previous rejections of the claims have relied upon sequences which could be sequenced using the predetermined flow ordering method of Garcia.  However, the amended claims do not appear to read on known sequences which would be sequenced using the method of Garcia, to the extent that such sequences could be searched.  Thus, the present invention appears to be free of the art.
Furthermore, the Applicants have reduced to practice the recited apparatus to sequence a fragment (Figure 7).  Such sequencing methodologies could therefore reasonably be applied to other sequences.  Furthermore, such sequencing apparatus, technologies, and methods are common as taught by Rothberg and Garcia:  a practitioner is therefore enabled to use the invention with a reasonable expectation of success.
Additionally, the Applicants have submitted a terminal disclaimer along with the present application in relation to their issued patent US 9,605,308.  Thus, the Applicant has nullified the original double patenting rejection.
Conclusion
Claims 21-39 are allowed.

APPLICANT REBUTTAL: R
EMARKS
I.
Claim Status:
Claims 21 and 24 are amended. Claims 1-20 and 40-50 are cancelled. After the foregoing amendments are entered into the record, claims 21 - 39 will be pending in this case.
Support for the claim amendments can be found in the application as-filed, e.g., at paragraphs [0037]
- [0044]. Thus, no new subject matter is added as a result of these amendments.
II.
Claim Re
j
ections Under 35 U.S.C.
Withdrawn:
Applicant thanks the Examiner for withdrawal of the rejection under 35 U.S.C. § 103.
III.
Claim Re
j
ections Under 35 U.S.C.
X
Claims 21-39 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.
In response, Applicant has amended claim 21 in accordance with the Examiner's recommendations for amendments to claim 21 on page 4 of the Office Action. Applicant respectfully asserts that claim 21, as amended, is definite. Claims 22-39 depend from claim 21 and are defimite for at least the same reason as claim 21. Applicant respectfully requests reconsideration and withdrawal of the rejection of claims 21-39 under 35 U.S.C. §112.
IV.
Claim Re
j
ections Under Double Patenting:
Claims 21-39 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,605,308.
Applicant respectfully traverses the above rejection. However, solely in an effort to expedite allowance and without acquiescing to the Action's grounds for rejection, Applicant submits a timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) herewith. Applicant requests that the nonstatutory obviousness-type double patenting rejection of claims 21-39 be withdrawn accordingly.
Conclusion


CITED REFERENCE SUMMARIES: Ref US20090127589: Claims:
1. An apparatus, comprising:
an array (100) of CMOS-fabricated sensors (105), each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150) and occupying an area on a surface of the array of approximately ten micrometers by ten micrometers or less.
2-20. (canceled)
21. A sensor array (100), comprising:
a two-dimensional array of electronic sensors (105) including at least 512 rows and at least 512 columns of the electronic sensors, each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150) configured to provide at least one output signal representing a presence and/or concentration of an analyte proximate to a surface of the two-dimensional array.
22-40. (canceled)
41. An apparatus, comprising:
an array (100) of CMOS-fabricated sensors (105), each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150), wherein the array of CMOS-fabricated sensors includes more than 256 sensors, wherein a collection of chemFET output signals from all chemFETs of the array constitutes a frame of data, and wherein the apparatus further comprises: control circuitry (110, 192, 194, 198) coupled to the array and configured to generate at least one array output signal (Vout) to provide multiple frames of data from the array at a frame rate of at least 1 frame per second.
42-50. (canceled)
51. An apparatus, comprising:
an array (100) of CMOS-fabricated sensors (105), each sensor comprising a chemically-sensitive field effect transistor (chemFET) (150), the chemFET comprising:
a floating gate structure (170); and
a source (156) and a drain (158) having a first semiconductor type and fabricated in a region (154) having a second semiconductor type, wherein there is no electrical conductor that electrically connects the region having the second semiconductor type to either the source or the drain.
52-73. (canceled)
74. An apparatus, comprising:
an array (100) of electronic sensors (105), each sensor consisting of three field effect transistors (FETs) including one chemically-sensitive field effect transistor (chemFET) (150).
75. (canceled)
76. An apparatus, comprising:
an array (100) of electronic sensors (105), each sensor comprising three or fewer field effect transistors (FETs), wherein the three or fewer FETs includes one chemically-sensitive field effect transistor (chemFET) (150).
77. An apparatus, comprising:
an array (100) of electronic sensors (105), each sensor comprising:
a plurality of field effect transistors (FETs) including one chemically-sensitive field effect transistor (chemFET) (150); and
a plurality of electrical conductors electrically connected to the plurality of FETs,
wherein the plurality of FETs are arranged such that the plurality of electrical conductors includes no more than four conductors traversing an area occupied by each sensor and interconnecting multiple sensors of the array.
78. An apparatus, comprising:
an array (100) of CMOS-fabricated sensors (105), each sensor comprising a plurality of field effect transistors (FETs) including one chemically-sensitive field effect transistor (chemFET) (150), wherein all of the FETs in each sensor are of a same channel type and implemented in a single semiconductor region of an array substrate.
79. (canceled)
80. A sensor array (100), comprising:
a plurality of electronic sensors (105) arranged in a plurality of rows and a plurality of columns, each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150) configured to provide at least one output signal representing a presence and/or a concentration of an analyte proximate to a surface of the array, wherein for each column of the plurality of columns, the array further comprises: column circuitry (110) configured to provide a constant drain current and a constant drain-to-source voltage to respective chemFETs in the column, the column circuitry including two operational amplifiers and a diode-connected FET arranged in a Kelvin bridge configuration with the respective chemFETs to provide the constant drain-to-source voltage.
81. A sensor array (100), comprising:
a plurality of electronic sensors (105) arranged in a plurality of rows and a plurality of columns, each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150) configured to provide at least one output signal representing a concentration of ions in an analyte proximate to a surface of the array; at least one row select shift register (192) to enable respective rows of the plurality of rows; and at least one column select shift register (194) to acquire chemFET output signals from respective columns of the plurality of columns.
82-85. (canceled)
86. An apparatus, comprising:
an array (100) of CMOS-fabricated sensors (105), each sensor comprising a chemically-sensitive field effect transistor (chemFET) (150), the chemFET comprising:
a floating gate structure (170); and
a source (156) and a drain (158) having a first semiconductor type and fabricated in a region (154) having a second semiconductor type, wherein there is no electrical conductor that electrically connects the region having the second semiconductor type to either the source or the drain,
 wherein: the array includes a two-dimensional array of at least 512 rows and at least 512 columns of the CMOS-fabricated sensors; each sensor consists of three field effect transistors (FETs) including the chemFET; each sensor includes a plurality of electrical conductors electrically connected to the three FETs; the three FETs are arranged such that the plurality of electrical conductors includes no more than four conductors traversing an area occupied by each sensor and interconnecting multiple sensors of the array; all of the FETs in each sensor are of a same channel type and implemented in a single semiconductor region of an array substrate; and a collection of chemFET output signals from all chemFETs of the array constitutes a frame of data, and wherein the apparatus further comprises: control circuitry (110, 192, 194, 198) coupled to the array and configured to generate at least one array output signal (Vout) to provide multiple frames of data from the array at a frame rate of at least 20 frames per second.
87. A method for processing an array (100) of CMOS-fabricated sensors (105), each sensor comprising a chemically-sensitive field effect transistor (chemFET) (150), the method comprising:
A) dicing a semiconductor wafer including the array to form at least one diced portion including the array; and B) performing a forming gas anneal on the at least one diced portion.
88-93. (canceled)
94. A method for processing an array (100) of CMOS-fabricated sensors (105), each sensor comprising a chemically-sensitive field effect transistor (chemFET) (150) having a chemically-sensitive passivation layer of silicon nitride and/or silicon oxynitride deposited via plasma enhanced chemical vapor deposition (PECVD), the method comprising:
A) depositing at least one additional passivation material on the chemically-sensitive passivation layer so as to reduce a porosity and/or increase a density of the passivation layer.
95-101. (canceled)
102. An apparatus comprising
a chemical-sensitive field effect transistor (chemFET) having disposed on its surface a PPi receptor.
103. A fluidics assembly for use with an array of sensors on an active semiconductor device capped with a protective layer, comprising:
a first member having therein an aperture for mating to the sensor array; and a second member fixed to the first member in a fluid-tight seal therebetween, and having first and second fluid ports for supporting fluid passage, the first and second members and the sensor array defining a fluid chamber, whereby fluid introduced into one of said ports flows over the array before exiting via the other of said ports.
104. A fluidics assembly for use with an array of sensors on an active semiconductor device capped with a protective layer, comprising:
a microwell array configured and arranged to provide fluid access to said protective layer; a first member having therein an aperture for mating to the sensor array around the microwell array; and a second member fixed to the first member in a fluid-tight seal therebetween, and having first and second fluid ports for supporting fluid passage, the first and second members and the microwell array defining a fluid chamber over the protective layer of the semiconductor device when mated to the sensor array, whereby fluid introduced into one of said ports flows over the microwell array before exiting via the other of said ports and the active semiconductor device senses chemical activity in at least some of the microwells in the microwell array.
105-106. (canceled)
Ref US9605308H: [content unavailable]