IP Library › Granted Patent US 12,203,129
Granted Patent B2
US 12,203,129 · App. 16/128,343 · Granted Jan 21, 2025

Formulations and signal encoding and decoding methods for massively multiplexed biochemical assays

Inventors: Christopher MacDonald (San Diego, CA); Aditya Rajagopal (Orange, CA); Paul Flook (San Diego, CA); Yaser Abu-Mostafa (Pasadena, CA); Dominic Yurk (Garden Grove, CA)
Assignee: ChromaCode, Inc.
C12Q1/6816
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Quick Facts
Patent No.
US 12,203,129
App. No.
16/128,343
Granted
Jan 21, 2025
Kind
B2
Abstract

The present disclosure provides methods and compositions for the multiplexed detection of multiple analytes from a sample. Analytes may be nucleic acid analytes. Detection of analytes may comprise contacting one or more sample subsets with hybridization probes, thereby generating one or more cumulative signal measurements capable of detecting the presence of absence of a plurality of analytes.

Claims (23)

1. A method of unambiguously detecting the presence or absence of at least three polynucleotide analytes in a sample, in any combination of presence or absence, the method comprising:

(a) providing a first reaction mixture comprising the sample and a first plurality of hybridization probes,

wherein a hybridization probe of the first plurality of hybridization probes is specific for an analyte of the at least three polynucleotide analytes, wherein the first plurality of hybridization probes comprises hybridization probes specific for at least two of the at least three polynucleotide analytes, wherein the hybridization probes specific for the at least two of the at least three polynucleotide analytes comprise a first fluorophore that is identical for the first plurality of hybridization probes, wherein a first hybridization probe generates a first signal intensity in an amplification reaction, wherein a second hybridization probe generates a second signal intensity in the amplification reaction different from the first signal intensity, wherein a signal intensity of the first reaction mixture in the amplification reaction corresponds to a combination of presence or absence of the at least three polynucleotide analytes, wherein at least one combination of analytes produces a same signal intensity as a second combination of analytes, thereby producing an ambiguity between at least two combinations of analytes;

(b) providing a second reaction mixture comprising the sample and a second plurality of hybridization probes,

wherein a hybridization probe of the second plurality of hybridization probes is specific for an analyte of the at least three polynucleotide analytes, wherein the second plurality of hybridization probes comprises hybridization probes specific for at least two of the at least three polynucleotide analytes, wherein the hybridization probes specific for the at least two of the at least three polynucleotide analytes comprise a second fluorophore that is identical for the second plurality of hybridization probes, wherein a third hybridization probe generates a third signal intensity in an amplification reaction, wherein a fourth hybridization probe generates a fourth signal intensity in the amplification reaction different from the third signal intensity, wherein a signal intensity of the second reaction mixture in the amplification reaction corresponds to a combination of presence or absence of the at least three polynucleotide analytes;

(c) generating the signal intensity of the first reaction mixture using a first amplification reaction and generating the signal intensity of the second reaction mixture using a second amplification reaction; and

(d) processing the signal intensity of the first reaction mixture and the signal intensity of the second reaction mixture to generate a combined output, wherein the combined output unambiguously identifies a given combination of presence or absence of the at least three polynucleotide analytes in the sample, thereby resolving the ambiguity.

2. The method of claim 1 , wherein a number of unique hybridization probes in the first plurality of hybridization probes is less than or equal to a number of unique polynucleotide analytes in the at least three polynucleotide analytes.

3. The method of claim 1 , wherein a number of unique hybridization probes in the second plurality of hybridization probes is less than or equal to a number of unique polynucleotide analytes in the at least three polynucleotide analytes.

4. The method of claim 1 , wherein the first plurality of hybridization probes and the second plurality of hybridization probes are oligonucleotide probes.

5. The method of claim 1 , wherein the method does not require any step of immobilization of the at least three polynucleotide analytes, microscopy, flow cytometry, physical separation of the at least three polynucleotide analytes, mass spectrometry, or melting curve analysis.

6. The method of claim 1 , wherein each hybridization probe of the first plurality of hybridization probes and the second plurality of hybridization probes comprises a fluorophore capable of being detected in the same optical channel.

7. The method of claim 1 , wherein each hybridization probe of the first plurality of hybridization probes and the second plurality of hybridization probes comprises an identical fluorophore.

8. The method of claim 1 , wherein each hybridization probe of the first plurality of hybridization probes and the second plurality of hybridization probes is provided at a different concentration.

9. The method of claim 1 , wherein the at least three polynucleotide analytes are at least seven polynucleotide analytes.

10. The method of claim 1 , wherein the method does not require any step of immobilization of the polynucleotide analytes, microscopy, flow cytometry, physical separation of the polynucleotide analytes, mass spectrometry, or melting curve analysis.

11. The method of claim 1 , wherein each of the first plurality of hybridization probes and the second plurality of hybridization probes corresponds to one of the at least three polynucleotide analytes.

12. The method of claim 1 , wherein each of the first plurality of hybridization probes and the second plurality of hybridization probes has complementarity to one of the at least three polynucleotide analytes.

13. The method of claim 1 , wherein the processing further comprises comparing said combined output to an expected value.

14. The method of claim 1 , wherein the first amplification reaction or second amplification reaction comprises a digital polymerase chain reaction.

15. The method of claim 14 , wherein prior to (c), the first reaction mixture or the second reaction mixture is divided into a plurality of partitions.

16. The method of claim 15 , wherein the plurality of partitions is a plurality of wells.

17. The method of claim 1 , wherein the first amplification reaction or second amplification reaction comprises a polymerase chain reaction.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 3, 2018
From: MACDONALD, CHRISTOPHER; RAJAGOPAL, ADITYA; FLOOK, PAUL; ABU-MOSTAFA, YASER; YURK, DOMINIC
To: CHROMACODE, INC.
Reel/Frame 047060/0458 →
Continuity (2)
Provisional Application 62693777 · Jul 3, 2018
Related Publication 20200010876A1 · Jan 9, 2020
References Cited (400)
US 5079351A · Sninsky et al. · 1992 [cited by applicant]
US 5538848A · Livak et al. · 1996 [cited by applicant]
US 5618711A · Gelfand et al. · 1997 [cited by applicant]
US 5677152A · Birch et al. · 1997 [cited by applicant]
US 5723591A · Livak et al. · 1998 [cited by applicant]
US 5773258A · Birch et al. · 1998 [cited by applicant]
US 5789224A · Gelfand et al. · 1998 [cited by applicant]
US 5804375A · Gelfand et al. · 1998 [cited by applicant]
US 5834203A · Katzir et al. · 1998 [cited by applicant]
US 5876930A · Livak et al. · 1999 [cited by applicant]
US 5882856A · Shuber · 1999 [cited by applicant]
US 5928862A · Morrison · 1999 [cited by applicant]
US 5948360A · Rao et al. · 1999 [cited by applicant]
US 5981180A · Chandler et al. · 1999 [cited by applicant]
US 5994056A · Higuchi · 1999 [cited by applicant]
US 6030787A · Livak et al. · 2000 [cited by applicant]
US 6057134A · Lader et al. · 2000 [cited by applicant]
US 6103463A · Chetverin · 2000 [cited by examiner]
US 6127155A · Gelfand et al. · 2000 [cited by applicant]
US 6171785B1 · Higuchi · 2001 [cited by applicant]
US 6248526B1 · Weimer · 2001 [cited by applicant]
US 6258569B1 · Livak et al. · 2001 [cited by applicant]
US 6379888B1 · Nadeau et al. · 2002 [cited by applicant]
US 6534266B1 · Singer · 2003 [cited by applicant]
US 6534274B2 · Becker et al. · 2003 [cited by applicant]
US 6548259B2 · Ward et al. · 2003 [cited by applicant]
US 6642062B2 · Kauvar et al. · 2003 [cited by applicant]
US 6893875B2 · Tsuji et al. · 2005 [cited by applicant]
US 7101663B2 · Godfrey et al. · 2006 [cited by applicant]
US 7141377B2 · Gelfand et al. · 2006 [cited by applicant]
US 7348141B2 · French et al. · 2008 [cited by applicant]
US 7385043B1 · Kramer · 2008 [cited by applicant]
US 7410764B2 · Gocke et al. · 2008 [cited by applicant]
US 7413708B2 · Mayrand · 2008 [cited by applicant]
US 7473767B2 · Dimitrov · 2009 [cited by applicant]
US 7507575B2 · Bedingham et al. · 2009 [cited by applicant]
US 7575864B2 · Bedzyk et al. · 2009 [cited by applicant]
US 7667024B2 · Mao et al. · 2010 [cited by applicant]
US 7671184B2 · Haener et al. · 2010 [cited by applicant]
US 7709249B2 · Bedingham et al. · 2010 [cited by applicant]
US 7767423B2 · Kopreski et al. · 2010 [cited by applicant]
US 7771949B2 · Kramer · 2010 [cited by applicant]
US 7919237B2 · Dimitrov et al. · 2011 [cited by applicant]
US 7919244B2 · Madejon et al. · 2011 [cited by applicant]
US 7930106B2 · Carrick · 2011 [cited by applicant]
US 7941279B2 · Hwang et al. · 2011 [cited by applicant]
US 8039215B2 · Higuchi et al. · 2011 [cited by applicant]
US 8148512B2 · Dimitrov et al. · 2012 [cited by applicant]
US 8426132B2 · Li et al. · 2013 [cited by applicant]
US 8455184B2 · Atchley et al. · 2013 [cited by applicant]
US 8492094B2 · Dimitrov et al. · 2013 [cited by applicant]
US 8519115B2 · Webster et al. · 2013 [cited by applicant]
US 8614061B2 · Brabetz et al. · 2013 [cited by applicant]
US 8771955B2 · Reed et al. · 2014 [cited by applicant]
US 8838394B2 · Kartalov et al. · 2014 [cited by applicant]
US 8877464B2 · Babiel et al. · 2014 [cited by applicant]
US 8962250B2 · Stanley · 2015 [cited by applicant]
US 9133506B2 · Katzir et al. · 2015 [cited by applicant]
US 9222128B2 · Saxonov et al. · 2015 [cited by applicant]
US 9260761B2 · Tyagi et al. · 2016 [cited by applicant]
US 9366632B2 · Link et al. · 2016 [cited by applicant]
US 9422593B2 · Rothmann et al. · 2016 [cited by applicant]
US 9441266B2 · Larson et al. · 2016 [cited by applicant]
US 9447457B2 · Chun et al. · 2016 [cited by applicant]
US 9458497B2 · Hassibi et al. · 2016 [cited by applicant]
US 9791372B2 · Malik et al. · 2017 [cited by applicant]
US 10066263B2 · Rajagopal et al. · 2018 [cited by applicant]
US 10068051B2 · Kartalov et al. · 2018 [cited by applicant]
US 10770170B2 · Kartalov · 2020 [cited by examiner]
US 20020022273A1 · Empedocles et al. · 2002 [cited by applicant]
US 20020132260A1 · Erlander · 2002 [cited by examiner]
US 20020146734A1 · Ortyn et al. · 2002 [cited by applicant]
US 20030134320A1 · Barrus · 2003 [cited by examiner]
US 20030148280A1 · Harris et al. · 2003 [cited by applicant]
US 20030148544A1 · Nie et al. · 2003 [cited by applicant]
US 20040023207A1 · Polansky · 2004 [cited by applicant]
US 20040053230A1 · Schaffer et al. · 2004 [cited by applicant]
US 20040180378A1 · Tozer · 2004 [cited by examiner]
US 20040191794A1 · Weindel et al. · 2004 [cited by applicant]
US 20040248082A1 · Scallon · 2004 [cited by applicant]
US 20050053950A1 · Zudaire et al. · 2005 [cited by applicant]
US 20050064435A1 · Su et al. · 2005 [cited by applicant]
US 20050106607A1 · Yin · 2005 [cited by examiner]
US 20050164264A1 · Shipwash · 2005 [cited by applicant]
US 20050214753A1 · Shultz et al. · 2005 [cited by applicant]
US 20050250146A1 · McMillan · 2005 [cited by applicant]
US 20050260640A1 · Andersen et al. · 2005 [cited by applicant]
US 20060039918A1 · Albani et al. · 2006 [cited by applicant]
US 20060216708A1 · Venema · 2006 [cited by applicant]
US 20070072211A1 · Newton et al. · 2007 [cited by applicant]
US 20070161043A1 · Nie et al. · 2007 [cited by applicant]
US 20070178485A1 · El-Deiry et al. · 2007 [cited by applicant]
US 20070231824A1 · Chee et al. · 2007 [cited by applicant]
US 20080003599A1 · Dary et al. · 2008 [cited by applicant]
US 20080050737A1 · Arieli et al. · 2008 [cited by applicant]
US 20080069733A1 · Maltezos et al. · 2008 [cited by applicant]
US 20080096767A1 · Kohn · 2008 [cited by examiner]
US 20080124705A1 · Kramer · 2008 [cited by applicant]
US 20090042735A1 · Blair et al. · 2009 [cited by applicant]
US 20090048785A1 · Katzir et al. · 2009 [cited by applicant]
US 20090062129A1 · McKernan et al. · 2009 [cited by applicant]
US 20100015607A1 · Geiss et al. · 2010 [cited by applicant]
US 20100041092A1 · Lin et al. · 2010 [cited by applicant]
US 20100047924A1 · Webster et al. · 2010 [cited by applicant]
US 20100112710A1 · Geiss et al. · 2010 [cited by applicant]
US 20100120043A1 · Sood · 2010 [cited by examiner]
US 20100129792A1 · Makrigiorgos · 2010 [cited by applicant]
US 20100151443A1 · Xiang et al. · 2010 [cited by applicant]
US 20100159447A1 · Li et al. · 2010 [cited by applicant]
US 20100210472A1 · Empedocles et al. · 2010 [cited by applicant]
US 20100233686A1 · Higuchi et al. · 2010 [cited by applicant]
US 20100248257A1 · Jacobsen et al. · 2010 [cited by applicant]
US 20100261026A1 · Ferree et al. · 2010 [cited by applicant]
US 20100267064A1 · Kartalov et al. · 2010 [cited by applicant]
US 20100273173A1 · Hirai et al. · 2010 [cited by applicant]
US 20100317005A1 · Hardin et al. · 2010 [cited by applicant]
US 20100324834A1 · Treptow et al. · 2010 [cited by applicant]
US 20110104684A1 · Hooper · 2011 [cited by applicant]
US 20110151459A1 · Rothmann et al. · 2011 [cited by applicant]
US 20110151550A1 · Sagner et al. · 2011 [cited by applicant]
US 20110171658A1 · Carrick · 2011 [cited by applicant]
US 20110183884A1 · Miller et al. · 2011 [cited by applicant]
US 20110207623A1 · Dimitrov et al. · 2011 [cited by applicant]
US 20110223602A1 · Whitman et al. · 2011 [cited by applicant]
US 20110237459A1 · Nova et al. · 2011 [cited by applicant]
US 20120003646A1 · Joo et al. · 2012 [cited by applicant]
US 20120040349A1 · Von Lode et al. · 2012 [cited by applicant]
US 20120040352A1 · Wangh et al. · 2012 [cited by applicant]
US 20120045756A1 · Rothmann et al. · 2012 [cited by applicant]
US 20120077195A1 · Li et al. · 2012 [cited by applicant]
US 20120077692A1 · Hassibi et al. · 2012 [cited by applicant]
US 20120101740A1 · Orpana et al. · 2012 [cited by applicant]
US 20120122704A1 · Atchley et al. · 2012 [cited by applicant]
US 20120141995A1 · Li et al. · 2012 [cited by applicant]
US 20120164652A1 · Clemens · 2012 [cited by examiner]
US 20120171677A1 · Ludowise · 2012 [cited by applicant]
US 20120184017A1 · Chatterjee · 2012 [cited by applicant]
US 20120190030A1 · Chun et al. · 2012 [cited by applicant]
US 20120196283A1 · Babiel et al. · 2012 [cited by applicant]
US 20120244534A1 · Ching et al. · 2012 [cited by applicant]
US 20120252014A1 · Loeffert et al. · 2012 [cited by applicant]
US 20120252015A1 · Hindson · 2012 [cited by examiner]
US 20120252017A1 · Reed et al. · 2012 [cited by applicant]
US 20120258457A1 · Jarosch et al. · 2012 [cited by applicant]
US 20120302448A1 · Hutchison et al. · 2012 [cited by applicant]
US 20130017971A1 · Geiss et al. · 2013 [cited by applicant]
US 20130040841A1 · Saxonov et al. · 2013 [cited by applicant]
US 20130078626A1 · Wasserstrom et al. · 2013 [cited by applicant]
US 20130116780A1 · Miller et al. · 2013 [cited by applicant]
US 20130178378A1 · Hatch · 2013 [cited by examiner]
US 20130209997A1 · Whitney et al. · 2013 [cited by applicant]
US 20130261019A1 · Lin et al. · 2013 [cited by applicant]
US 20130288244A1 · Deciu et al. · 2013 [cited by applicant]
US 20140004520A1 · Mohapatra · 2014 [cited by examiner]
US 20140038195A1 · Malik et al. · 2014 [cited by applicant]
US 20140171341A1 · Jouvenot et al. · 2014 [cited by applicant]
US 20140213471A1 · Rajagopal et al. · 2014 [cited by applicant]
US 20140274774A1 · Li et al. · 2014 [cited by applicant]
US 20150057178A1 · Kartalov et al. · 2015 [cited by applicant]
US 20150072887A1 · Chun et al. · 2015 [cited by applicant]
US 20150111776A1 · Chen · 2015 [cited by applicant]
US 20150140554A1 · Snyder et al. · 2015 [cited by applicant]
US 20150211054A1 · Kostem · 2015 [cited by examiner]
US 20150275295A1 · Wang et al. · 2015 [cited by applicant]
US 20160040249A1 · Ceppi · 2016 [cited by examiner]
US 20160040256A1 · Chen et al. · 2016 [cited by applicant]
US 20160108464A1 · Saxonov et al. · 2016 [cited by applicant]
US 20160201122A1 · Bushkin · 2016 [cited by examiner]
US 20160273048A1 · Roperch · 2016 [cited by applicant]
US 20160281130A1 · Dahl · 2016 [cited by examiner]
US 20170145490A1 · Chiu et al. · 2017 [cited by applicant]
US 20170314073A1 · Grömminger et al. · 2017 [cited by applicant]
US 20170362636A1 · Rajagopal et al. · 2017 [cited by applicant]
US 20180030551A1 · Rajagopal et al. · 2018 [cited by applicant]
US 20180052110A1 · Malik et al. · 2018 [cited by applicant]
US 20180057864A1 · Jacky et al. · 2018 [cited by applicant]
US 20190002963A1 · Rajagopal · 2019 [cited by applicant]
US 20190032112A1 · Rajagopal et al. · 2019 [cited by applicant]
US 20190112636A1 · Rajagopal et al. · 2019 [cited by applicant]
US 20190233882A1 · Jacky et al. · 2019 [cited by applicant]
US 20200087709A1 · Bracht et al. · 2020 [cited by applicant]
CN 1172530A · 1998 [cited by applicant]
CN 1936019A · 2007 [cited by applicant]
CN 101570782A · 2009 [cited by applicant]
CN 101646786A · 2010 [cited by applicant]
CN 101831496A · 2010 [cited by applicant]
CN 102269759A · 2011 [cited by applicant]
CN 102439171A · 2012 [cited by applicant]
CN 102559868A · 2012 [cited by applicant]
CN 102576390A · 2012 [cited by applicant]
CN 103293299A · 2013 [cited by applicant]
CN 104404162A · 2015 [cited by applicant]
CN 106148521A · 2016 [cited by applicant]
CN 106636409A · 2017 [cited by applicant]
CN 104662172B · 2018 [cited by applicant]
EP 0519338A1 · 1992 [cited by applicant]
EP 1087020A2 · 2001 [cited by applicant]
EP 1448581B1 · 2008 [cited by applicant]
EP 2224017A1 · 2010 [cited by applicant]
EP 1963531B1 · 2011 [cited by applicant]
EP 1629108B1 · 2014 [cited by applicant]
GB 2526445A · 2015 [cited by applicant]
JP 2005508493A · 2005 [cited by applicant]
JP 2007525184A · 2007 [cited by applicant]
WO WO9624044A1 · 1996 [cited by applicant]
WO WO9746714A1 · 1997 [cited by applicant]
WO WO9919515A1 · 1999 [cited by applicant]
WO WO9952708A1 · 1999 [cited by applicant]
WO WO0107640A2 · 2001 [cited by applicant]
WO WO0159144A1 · 2001 [cited by applicant]
WO WO02056014A2 · 2002 [cited by applicant]
WO WO03002979A2 · 2003 [cited by applicant]
WO WO03003015A2 · 2003 [cited by applicant]
WO WO03020967A1 · 2003 [cited by applicant]
WO WO02056014A3 · 2003 [cited by applicant]
WO WO2004087950A2 · 2004 [cited by applicant]
WO WO2004099434A2 · 2004 [cited by applicant]
WO WO2006079049A2 · 2006 [cited by applicant]
WO WO2006138679A2 · 2006 [cited by applicant]
WO WO2007076128A2 · 2007 [cited by applicant]
WO WO2007076129A2 · 2007 [cited by applicant]
WO WO2007076132A2 · 2007 [cited by applicant]
WO WO2007076132A3 · 2007 [cited by applicant]
WO WO2007076128A3 · 2007 [cited by applicant]
WO WO2007139766A2 · 2007 [cited by applicant]
WO WO2007076129A3 · 2008 [cited by applicant]
WO WO2008118998A2 · 2008 [cited by applicant]
WO WO2008124847A2 · 2008 [cited by applicant]
WO WO2007139766A3 · 2008 [cited by applicant]
WO WO2008124847A3 · 2009 [cited by applicant]
WO WO2009036514A2 · 2009 [cited by applicant]
WO WO2009081967A1 · 2009 [cited by applicant]
WO WO2010007355A1 · 2010 [cited by applicant]
WO WO2010013017A1 · 2010 [cited by applicant]
WO WO2010017543A1 · 2010 [cited by applicant]
WO WO2010019826A1 · 2010 [cited by applicant]
WO WO2010075413A1 · 2010 [cited by applicant]
WO WO2010128206A1 · 2010 [cited by applicant]
WO WO2011047087A2 · 2011 [cited by applicant]
WO WO2011047087A3 · 2011 [cited by applicant]
WO WO2011100541A2 · 2011 [cited by applicant]
WO WO2011116088A2 · 2011 [cited by applicant]
WO WO2011100541A3 · 2012 [cited by applicant]
WO WO2011116088A3 · 2012 [cited by applicant]
WO WO2012056227A2 · 2012 [cited by applicant]
WO WO2012058638A2 · 2012 [cited by applicant]
WO WO2012106428A2 · 2012 [cited by applicant]
WO WO2012135340A2 · 2012 [cited by applicant]
WO WO2012058638A3 · 2012 [cited by applicant]
WO WO2012135340A3 · 2012 [cited by applicant]
WO WO2013096851A1 · 2013 [cited by applicant]
WO WO2013116780A1 · 2013 [cited by applicant]
WO WO2014022827A1 · 2014 [cited by applicant]
WO WO2014116884A1 · 2014 [cited by applicant]
WO WO2014149480A1 · 2014 [cited by applicant]
WO WO2014164874A2 · 2014 [cited by applicant]
WO WO2015147370A1 · 2015 [cited by applicant]
WO WO2016154600A1 · 2016 [cited by examiner]
WO WO2016172632A2 · 2016 [cited by applicant]
WO WO2017139354A1 · 2017 [cited by applicant]
WO WO2017173035A1 · 2017 [cited by applicant]
WO WO2017218777A1 · 2017 [cited by applicant]
WO WO2018081178A1 · 2018 [cited by applicant]
WO WO2019006023A1 · 2019 [cited by applicant]
WO WO2019079204A1 · 2019 [cited by applicant]
WO WO2019169043A1 · 2019 [cited by applicant]
WO WO2019204357A1 · 2019 [cited by applicant]
WO WO2019236447A1 · 2019 [cited by applicant]
WO WO2020010137A1 · 2020 [cited by applicant]
WO WO2020014388A1 · 2020 [cited by applicant]
WO WO2020051521A1 · 2020 [cited by applicant]
WO WO2021211613A1 · 2021 [cited by applicant]
WO WO2023014898A1 · 2023 [cited by applicant]
Rajagopal, et al. Anal. Chem., vol. 85, pp. 7629-7636, published Jun. 13, 2013. [cited by examiner]
Beige, et al. Clinical evaluation of a [cited by applicant]
Chamberlain, et al. Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res. Dec. 9, 1988;16(23):11141-56. [cited by applicant]
Chapin et al., Rapid microRNA profiling on encoded gel microparticles. Angewandte Chemie International Edition, 50(10):2289-2293, 2011. [cited by applicant]
Chen, et al. A Homogeneous, ligase-mediated DNA diagnostic test. Genome Research, 1998, vol. 8, pp. 549-556. [cited by applicant]
Chong, et al. Single-tube multiplex-PCR screen for common deletional determinants of alpha-thalassemia. Blood. Jan. 1, 2000;95(1):360-2. [cited by applicant]
Chromatogram, 2011, 2 pages. Dorland's illustrated medical dictionary. Retrieved online on Jan. 22, 2014 from «http://www.credoreference.com». [cited by applicant]
Chun, et al. Dual priming oligonucleotide system for the multiplex detection of respiratory viruses and SNP genotyping of CYP2C19 gene. Nucleic Acids Res. 2007;35(6):e40. Epub Feb. 7, 2007. [cited by applicant]
Co-pending U.S. Appl. No. 15/914,356, filed Mar. 7, 2018. [cited by applicant]
Craig, et al. Ordering of cosmid clones covering Herpes simplex virus type I (HSV-I) genome: a test case for fingerprinting by hybridisation. Nucleic Acids Research, 1990, vol. 18, pp. 2653-2660. [cited by applicant]
Dos Santos, et al. A simple one-step real-time RT-PCR for diagnosis of dengue virus infection. J Med Virol. Aug. 2008;80(8):1426-33. doi: 10.1002/jmv.21203. [cited by applicant]
El-Hajj, et al. Detection of rifampin resistance in [cited by applicant]
EMBL-Bank: AJ303204. http://www.ebi.ac.uk/Tools/dbfetch/emblfetch?db=embl&id=AJ303204&format=default&style=default&Retrieve=Retrieve. Accessed Feb. 2012. [cited by applicant]
EMBL-Bank: GQ395623. http://www.ebi.ac.uk/Tools/dbfetch/emblfetch?db=embl&id=GQ395623&format=default&style=default&Retrieve=Retrieve. Accessed Feb. 2012. [cited by applicant]
European Patent Application No. 13744261.2 Extended European Search Report dated May 3, 2016. [cited by applicant]
Evans et al. Digital PCR for Noninvasive Detection of Aneuploidy: Power Analysis Equations for Feasibility. Fetal Diagn. Ther. 31:244-247(2012). [cited by applicant]
Fodor, et al. Multiplexed biochemical assays with biological chips. Nature. Aug. 5, 1993;364(6437):555-6. [cited by applicant]
Fortina, et al. Digital mRNA profiling. Nat Biotechnol. Mar. 2008;26(3):293-4. doi: 10.1038/nbt0308-293. [cited by applicant]
Gandelman, et al., Novel Bioluminescent Quantitative Detection of Nucleic Acid Amplification in Real-Time, PLoS One, 2010, 5(11):e14155, 14 pages. [cited by applicant]
GenBank: M93130.1. Dengue type 3 virus complete genome RNA, complete cds. http://www.ncbi.nlm.nih.gov/nuccore/M93130. Accessed Feb. 2012. [cited by applicant]
Hartman, et al. Development of a novel internal positive control for Taqman based assays. Mol Cell Probes. Feb. 2005;19(1):51-9. Epub Dec. 10, 2004. [cited by applicant]
Heidari, et al. Detection of Plasmodium falciparum Directly from Blood Samples Using the Polymerase Chain Reaction. Journal of Sciences, Islamic Republic of Iran. 2005 16(1):21-24. [cited by applicant]
Henegariu, et al. Multiplex PCR: critical parameters and step-by-step protocol. Biotechniques. Sep. 1997;23(3):504-11. [cited by applicant]
HIV databases. http://www.hiv.lanl.gov/content/index. Accessed Feb. 2012. [cited by applicant]
Holland, et al., Detection of specific polymerase chain reaction product by utilizing the 5′ to 3′ exonuclease activity of Thermus aquaticus DNA polymerase. PNAS (USA) 88:7276-7280, 1991. [cited by applicant]
Horejsh, et al. A molecular beacon, bead-based assay for the detection of nucleic acids by flow cytometry. Nucleic Acids Res. Jan. 19, 2005;33(2):e13. [cited by applicant]
Huang, et al. Identification of 8 foodborne pathogens by multicolor combinational probe coding technology in a single real-time PCR. Clin Chem. Oct. 2007;53(10):1741-8. Epub Aug. 10, 2007. [cited by applicant]
Huang, et al. Multicolor combinatorial probe coding for real-time PCR. PLoS One. Jan. 14, 2011;6(1):e16033. doi: 10.1371/journal.pone.0016033. [cited by applicant]
International Search Report and Written Opinin dated Nov. 16, 2017 for International PCT Patent Application No. PCT/US2017/37682. [cited by applicant]
International search report and written opinion dated Apr. 12, 2013 for PCT/US2013/024509. [cited by applicant]
International search report and written report dated Jun. 22, 2017 for PCT Application No. PCT/US2017/24933. [cited by applicant]
Jothikumar, et al. Design of FRET-TaqMan probes for multiplex real-time PCR using an internal positive control. Biotechniques. Jun. 2009;46(7):519-24. doi: 10.2144/000113127. [cited by applicant]
Klostranec et al., Convergence of quantum dot barcodes with microfluidics and signal processing for multiplexed high-throughout infectious disease diagnostics. Nano Letters, 7(9):2812-2818, 2007. [cited by applicant]
Kuhn, et al. Hybridization of DNA and PNA molecular beacons to single-stranded and double-stranded DNA targets. J Am Chem Soc. Feb. 13, 2002;124(6):1097-103. [cited by applicant]
Lao, et al. Multiplexing RT-PCR for the detection of multiple miRNA species in small samples. Biochem Biophys Res Commun. Apr. 28, 2006;343(1):85-9. Epub Feb. 28, 2006. [cited by applicant]
Lee, et al. Novel multiplex PCR using dual-priming oligonucleotides for detection and discrimination of the [cited by applicant]
Lee, et al. Seven-color, homogeneous detection of six PCR products. Biotechniques. Aug. 1999;27(2):342-9. [cited by applicant]
Li et al., Multiplexed detection of pathogen DNA with DNA-based fluorescence nanobarcodes. Nature Biotechnology, 23(7):885-889, 2005. [cited by applicant]
Liew, et al. Validating a custom multiplex ELISA against individual commercial immunoassays using clinical samples. Biotechniques. Mar. 2007;42(3):327-8, 330-3. [cited by applicant]
Lin et al., Self-assembled combinatorial encoding nanoarrays for multiplexed biosensing. Nano Letters, 7(2):507-512, 2007. [cited by applicant]
Livak, et al. Oligonucleotides with fluorescent dyes at opposite ends provide a quenched probe system useful for detecting PCR product and nucleic acid hybridization. PCR Methods Appl. Jun. 1995;4(6):357-62. [cited by applicant]
Morrison, et al. Two-color ratio-coding of chromosome targets in fluorescence in situ hybridization: quantitative analysis and reproducibility. Cytometry. Apr. 1, 1997;27(4):314-26. [cited by applicant]
Noordhoek, et al. Sensitivity and specificity of PCR for detection of [cited by applicant]
Notice of allowance dated Jun. 2, 2014 for U.S. Appl. No. 13/756,760. [cited by applicant]
Office action dated Jan. 24, 2014 for U.S. Appl. No. 13/756,760. [cited by applicant]
Office action dated Jun. 6, 2017 for U.S. Appl. No. 14/451,876. [cited by applicant]
Office action dated Nov. 23, 2016 for U.S. Appl. No. 14/451,876. [cited by applicant]
Oliveira, et al. Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant [cited by applicant]
Ou, et al. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. Jan. 15, 1988;239(4837):295-7. [cited by applicant]
Paton, et al. Detection and characterization of Shiga toxigenic [cited by applicant]
Patterson, et al. Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry. Science. May 14, 1993;260(5110):976-9. [cited by applicant]
Petersen, et al. Short PNA molecular beacons for real-time PCR allelic discrimination of single nucleotide polymorphisms. Mol Cell Probes. Apr. 2004;18(2):117-22. [cited by applicant]
Plasmodium falciparum (Plasmodium falciparum) Genome Browser Gateway. http://microbes.ucsc.edu/cgi-bin/hgGateway?hgsid=612764&clade=eukaryota-protista&org=0&db=0. Accessed Feb. 2012. [cited by applicant]
Ptak, et al. Inhibition of human immunodeficiency virus type 1 replication in human cells by Debio-025, a novel cyclophilin binding agent. Antimicrob Agents Chemother. Apr. 2008;52(4):1302-17. doi: 10.1128/AAC.01324-07.… [cited by applicant]
Rosenstraus, et al. An internal control for routine diagnostic PCR: design, properties, and effect on clinical performance. J Clin Microbiol. Jan. 1998;36(1):191-7. [cited by applicant]
Roth, et al. Feasibility and efficacy of routine PCR screening of blood donations for hepatitis C virus, hepatitis B virus, and HIV-1 in a blood-bank setting. Lancet. Jan. 30, 1999;353(9150):359-63. [cited by applicant]
Sambrook, et al. Molecular Cloning: A Laboratory Manual. 2nd Edition, 1989. [cited by applicant]
Sanger, et al. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. Dec. 1977;74(12):5463-7. [cited by applicant]
U.S. Appl. No. 15/623,974 Notice of Allowance dated Jul. 3, 2018. [cited by applicant]
Hudecova, I. et al. Maternal Plasma Fetal DNA Fractions in Pregnancies with Low and High Risks for Fetal Chromosomal Aneuploidies. PLoS ONE 9(2): e88484. [cited by applicant]
Speicher, et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nat Genet. Apr. 1996;12(4):368-75. [cited by applicant]
Tirasophon, et al. A novel detection of a single Plasmodium falciparum in infected blood. Biochem Biophys Res Commun. Feb. 28, 1991;175(1):179-84. [cited by applicant]
Tyagi, et al. Multicolor molecular beacons for allele discrimination. Nat Biotechnol. Jan. 1998;16(1):49-53. [cited by applicant]
Tyagi, et al. Wavelength-shifting molecular beacons. Nat Biotechnol. Nov. 2000;18(11):1191-6. [cited by applicant]
Urdea, et al. Requirements for high impact diagnostics in the developing world. Nature. Nov. 23, 2006;444 Suppl 1:73-9. [cited by applicant]
U.S. Appl. No. 15/677,772 Final Office Action Mailed Jun. 7, 2018. [cited by applicant]
U.S. Appl. No. 15/677,772 Non-Final Office Action Mailed Feb. 8, 2018. [cited by applicant]
U.S. Appl. No. 15/892,245 Preinterview First Interview Office Action Mailed May 11, 2018. [cited by applicant]
U.S. Appl. No. 14/451,876 Notice of Allowance dated Jul. 11, 2018. [cited by applicant]
U.S. Appl. No. 14/451,876 Notice of Allowance dated Jun. 14, 2018. [cited by applicant]
U.S. Appl. No. 15/623,974 Office Action dated Feb. 22, 2018. [cited by applicant]
U.S. Appl. No. 15/677,772 Office Action dated Feb. 8, 2018. [cited by applicant]
Vet, et al. Multiplex detection of four pathogenic retroviruses using molecular beacons. Proc Natl Acad Sci U S A. May 25, 1999;96(11):6394-9. [cited by applicant]
Wang, et al. Locked nucleic acid molecular beacons. J Am Chem Soc. Nov. 16, 2005;127(45):15664-5. [cited by applicant]
Waters, et al. Microchip device for cell lysis, multiplex PCR amplification, and electrophoretic sizing. Anal Chem. Jan. 1, 1998;70(1):158-62. [cited by applicant]
Weidmann, et al. Rapid detection of herpes simplex virus and varicella-zoster virus infections by real-time PCR. J Clin Microbiol. Apr. 2003;41(4):1565-8. [cited by applicant]
Wiese, et al. Simultaneous multianalyte ELISA performed on a microarray platform. Clin Chem. Aug. 2001;47(8):1451-7. [cited by applicant]
Xu et al., Multiplexed SNP genotyping using the Qbead system: a quantum dot-encoded microspere-based assay. Nucleic Acids Research, 31(8):e43, 2003. [cited by applicant]
Yang, L. et al. A novel universal real-time PCR system using the attached universal duplex probes for quantitative analysis of nucleic acids. BMC Molecular Biology, 9:54 (1-13) Jun. 4, 2008. [cited by applicant]
Zhang, et al. A novel real-time quantitative PCR method using attached universal template probe. Nucleic Acids Res. Oct. 15, 2003;31(20):e123(pp. 1-8). [cited by applicant]
Zhang, et al. Novel Multiplex PCR Assay for Characterization and Concomitant Subtyping of Staphylococcal Cassette Chromosome mec Types I to V in Methicillin-Resistant [cited by applicant]
International Application No. PCT/US18/39846 International Search Report and Written Opinion Mailed Sep. 14, 2018. [cited by applicant]
Saiki, et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science, 239(4839):487-491 (Jan. 29, 1988). [cited by applicant]
Blacket et al. Universal primers for fluorescent labeling of PCR fragments—an efficient and cost-effective approach to genotyping by fluorescence. Molecular Ecology Resources 12(3):456-463 (2012) Epub Jan. 24, 2012. [cited by applicant]
Co-pending U.S. Appl. No. 16/537,415, filed Aug. 9, 2019. [cited by applicant]
EP17814096.8 Extended European Search Report dated Dec. 2, 2019. [cited by applicant]
EP1818686.9 Extended Search Report dated Jul. 23, 2019. [cited by applicant]
European Office Action for Patent Application No. EP13824744.0 dated Nov. 6, 2018. [cited by applicant]
Extended European Search Report for Patent Application No. EP13824744.0 dated Feb. 26, 2016. [cited by applicant]
First Office Action for Chinese Patent Application No. 201380049844.9 dated Dec. 28, 2015 (w/translation). [cited by applicant]
Fu et al. Multiplex detection and SNP genotyping in a single fluorescence channel. PLoS One 7(1):Article No. e30340 (Jan. 2012). [cited by applicant]
Han, et al., Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nature Biotechnology 19.99 (Jul. 2001): 631-635. [cited by applicant]
Haustein et al. Fluorescence correlation spectroscopy: novel variations of an established technique. Ann Rev Biophys Biomol Struct 36:151-69 (2007). [cited by applicant]
PCT/US19/40392 International Search Report and Written Opinion dated Nov. 6, 2019. [cited by applicant]
PCT/US2013/053512 International Search Report and Written Opinion dated Oct. 16, 2013. [cited by applicant]
Rajagopal et al. Supercolor Coding Methods for Large-Scale Multiplexing of Biochemical Assays. Analytical Chemistry 85:7629-7636 (2013). [cited by applicant]
Second Office Action for Chinese Patent Application No. 201380049844.9 dated Sep. 19, 2016 (w/translation). [cited by applicant]
ThermoFisher Scientific Fluorescence SpectraViewer. Retrieved from http://www.thermofisher.com/us/en/home/life-science/cell-analysis/labeling-chemistry/fluorescence-spectraviewer.html on Sep. 25, 2015. [cited by applicant]
U.S. Appl. No. 13/958,479 Office Action dated Mar. 1, 2016. [cited by applicant]
U.S. Appl. No. 15/892,245 First Action Interview—Office Action mailed Jul. 19, 2018. [cited by applicant]
U.S. Appl. No. 16/128,343 Office Action dated Oct. 15, 2019. [cited by applicant]
U.S. Appl. No. 15/914,356 Office Action dated Jul. 22, 2019. [cited by applicant]
U.S. Appl. No. 15/914,356 Office Action dated Mar. 8, 2019. [cited by applicant]
Vogelstein, et al., Digital PCR, PNAS Aug. 3, 1999 96 (16) 9236-9241; https://doi.org/10.1073/pnas.96.16.9236. [cited by applicant]
Zhao et al. Comprehensive Algorithm for Quantitative Real-Time Polymerase Chain Reaction. Journal of Computational Biology 12(8):1047-1064 (2005). [cited by applicant]
Arya, et al., Basic principles of real-time quantitative PCR, 2005, Expert Rev. Mol. Diagn., 5(2), p. 209-219. [cited by applicant]
Co-pending U.S. Appl. No. 16/864,744, inventors Kartalovemil; P. et al., filed May 1, 2020. [cited by applicant]
European Patent Application No. 17776626 Office Action dated Oct. 18, 2019. [cited by applicant]
International Search Report and Written Opinion dated Nov. 21, 2019 for PCT/US2019/050050. [cited by applicant]
Loftis et al., Principles of real-time PCR. Veterinary PCR Diagnostics pp. 3-17 (2012). [cited by applicant]
Logan, et al., An Overview of real-time PCR platforms. 2004, In Real-time PCR: An essential guide, p. 13-30. [cited by applicant]
Morgan et al., A commercial line probe assay for the rapid detection of rifampicin resistance in [cited by applicant]
Navarro et al., Real-time PCR detection chemistry. Clin Chim Acta. 439:231-250 (2015). [cited by applicant]
PCT/US2018/039846 International Preliminary Report on Patentability dated Dec. 31, 2019. [cited by applicant]
PCT/US2018/055927 International Preliminary Report on Patentability dated Apr. 21, 2020. [cited by applicant]
PCT/US2019/019906 International Preliminary Report on Patentability Sep. 1, 2020. [cited by applicant]
PCT/US2019/019906 International Search Report and Written Opinion dated May 6, 2019. [cited by applicant]
PCT/US2019/027751 International Preliminary Report on Patentability dated Oct. 20, 2020. [cited by applicant]
PCT/US2019/027751 International Search Report and Written Opinion dated Jun. 26, 2019. [cited by applicant]
PCT/US2019/035129 Invitation to Pay Additional Fees dated Aug. 19, 2019. [cited by applicant]
PCT/US2019/041239 International Search Report and Written Opinion dated Sep. 30, 2019. [cited by applicant]
Pierce, et al. Linear-After-The-Exponential (LATE)-PCR: primer design criteria for high yields of specific single-stranded DNA and improved real-time detection. Proc Natl Acad Sci U S A. Jun. 14, 2005;102(24):8609-14. E… [cited by applicant]
Rajagopal et al., Significant Expansion of Real-Time PCR Multiplexing with Traditional Chemistries using Amplitude Modulation. Scientific Reports. 9(1): 1053 (2019). [cited by applicant]
Rickert et al., “Multiplexed Real-Time PCR Using Universal Reporters,” Clin. Chem., 50(9):1680-1683, 2004. [cited by applicant]
U.S. Appl. No. 15/892,245 Office Action dated Dec. 31, 2018. [cited by applicant]
U.S. Appl. No. 16/020,673 Non-Final Office Action dated Nov. 27, 2020. [cited by applicant]
U.S. Appl. No. 15/892,245 Office Action dated Dec. 11, 2019. [cited by applicant]