THAT ARE NOT ALLOLLIKULTTUUS009958363B2 (12 ) United States Patent ( 10 ) Patent No. : US 9 , 958 ,363 B2 Smart et al. (45 ) Date of Patent: May 1 , 2018 ( 54 ) FLUOROUS AFFINITY EXTRACTION FOR (56 ) References Cited IONIC LIQUID - BASED SAMPLE PREPARATION U . S . PATENT DOCUMENTS 7 ,273 ,587 B1 9 / 2007 Birkner et al . ( 71 ) Applicant: Agilent Technologies , Inc. , Loveland , 7 ,273 ,720 B1 9 / 2007 Birkner et al. CA (US ) ( Continued ) ( 72 ) Inventors: Brian Phillip Smart, San Jose , CA (US ) ; Brooks Bond - Watts , Fremont, FOREIGN PATENT DOCUMENTS CA (US ) ; James Alexander Apffel, Jr ., WO WO2007110637 10 /2007 Mountain View , CA (US ) WO WO2011155829 12 / 2011 ( 73 ) Assignee : Agilent Technologies , Inc ., Santa Clara , OTHER PUBLICATIONS CA (US ) Yuesheng Ye , Yossef A . Elabd “ Anion exchanged polymerized ionic ( * ) Notice : Subject to any disclaimer, the term of this liquids: High free volume single ion conductors ” Polymer 52 ( 2011 ) patent is extended or adjusted under 35 1309 - 1317 , plus supplementary data ( pp . 1 - 6 ) . * U . S . C . 154 (b ) by 168 days . (Continued ) ( 21) Appl . No. : 14 /724 ,656 Primary Examiner — Christine T Mui ão( 22 ) Filed : May 28 , 2015 Assistant Examiner - Emily R . Berkeley (6565 ) Prior Publication Data (57 ) ABSTRACT US 2015 /0369711 A1 Dec . 24 , 2015 A method for removing an ionic liquid from an aqueous Related U . S . Application Data sample is provided . In some embodiments , the method includes : ( a ) combining an aqueous sample including an ( 60 ) Provisional application No . 62/ 016 ,000 , filed on Jun . ionic liquid with an ion exchanger composition including an 23 , 2014 , provisional application No . 62 /016 , 003 , ion exchanger counterion to produce a solution including a (Continued ) fluorous salt of the ionic liquid , where at least one of the ionic liquid and the ion exchanger counterion is fluorinated ; (51 ) Int . Cl. ( b ) contacting the solution with a fluorous affinity material, GOIN 1 / 00 ( 2006 . 01 ) thereby removing fluorous salt from the solution and pro GOIN 1 / 34 ( 2006 . 01 ) ducing an aqueous eluate ; and ( c ) collecting the aqueous (Continued ) eluate . In certain embodiments, the method further includes: ( 52 ) U . S . CI. contacting a cell with an ionic liquid composition to lyse the CPC .. .. .. GOIN 1 / 34 (2013 .01 ) ; B01D 11/ 04 cell and produce an aqueous sample ; and contacting the ( 2013 .01 ); GOIN 1/ 405 ( 2013. 01 ) ; GOIN aqueous sample with a reverse phase substrate , thereby 1 /4055 (2013 .01 ) ; adsorbing proteins and / or lipids of the cell on the substrate . (Continued ) Compositions, kits and systems for practicing the subject ( 58 ) Field of Classification Search methods are also provided . CPC . .. .. .. .. .. .. .. .. GOIN 1 / 34 (Continued ) 15 Claims, 14 Drawing Sheets Ion Exchanger Teg. LiNF , Hydrophilic IL A Hydrophilic Aqueous sample metabolites : Organic Lipids Hydrophetic 1L w hydrophilic analytes Alkyny ! solid phase , Could be simple alkyre accorctyne. to go N . Azide - containing Solid phase alkyne , Remaining ionic liquid renoved , i ionic liquid . shown as cyclooctyne . front aqueous layer. US 9 , 958 , 363 B2 Page 2 Related U . S . Application Data 2009 /0004048 AL 1 /2009 Elliott et al. 2011/ 0124034 A15 / 2011 Kuehnle et al . filed on Jun . 23 , 2014 , provisional application No . 2011/ 0192793 A1* 8 / 2011 Chew .. C12N 1 /06 62 / 049 ,285 , filed on Sep . 11 , 2014 , provisional ap 210 /633 plication No . 62 / 051, 804 , filed on Sep . 17 , 2014 . 2014 /0273080 A1 9 /2014 Apffel , Jr. ( 51 ) Int . Cl. OTHER PUBLICATIONS B01D 11 /04 ( 2006 .01 ) Wei Ren , Aaron M . Scurto “ Phase equilibria of imidazolium ionic GOIN 1 / 40 ( 2006 .01 ) liquids and the refrigerant gas , 1 , 1 , 1 , 2 - tetrafluoroethane ( R - 134a )” (52 ) U . S . CI. Fluid Phase Equilibria 286 ( 2009 ) 1 - 7 . * CPC . .. .. Y10T 436 / 145555 ( 2015 .01 ); Y10T Mark B . Shiflett and A . Yokozeki “ Liquid - Liquid Equilibria of 436 / 147777 ( 2015 .01 ) ; Y1OT 436 / 24 ( 2015 .01 ) Hydrofluoroethers and Ionic Liquid 1 - Ethyl- 3 -methylimidazolium (58 ) Field of Classification Search Bis ( trifluoromethylsulfonyl ) imide” J . Chem . Eng. Data 2007 , 52 , USPC . .. .. .. .. .. .. 436 / 178 2413 - 2418 . * Lu , et al. , “ A Bioelectrochemical Method for the Quantitative See application file for complete search history . Description of the Hofmeister Effect of Ionic Liquids in Aqueous Solution ” , J . Phys . Chem ., 2012 , 116 , 11075 - 11080 . ( 56 ) References Cited Rezaee , et al. , “ Determination of organic compounds in water using dispersive liquid - liquid microextraction ” , Journal of Chromatogra U . S . PATENT DOCUMENTS phy A , 1116 , 2006 , 1 - 9 . 8 ,143 ,381 B2 * 3 /2012 Von Hagen . .. .. CO7K 14 / 705 Shahriari , et al ., “ Role of the Hofmeister Series in the Formation of 530 / 350 Ionic - Liquid - Based Aqueous Biphase Systems” , J . Phys . Chem ., 8 , 211 ,307 B2 7 / 2012 Chew et al. 2012 , 116 , 7252 - 7258 . 2002 /0072619 Al * 6 /2002 Bonrath . C07D 311/ 72 Yao , et al. , “ Dispersive liquid - liquid microextraction using an in situ 549 /411 metathesis reaction to form an ionic liquid extraction phase for the 2006 /0178507 A1 * 8 / 2006 Berry .. .. .. .. C07B 63 /00 preconcentration of aromatic compounds from water ” , Anal Bioanal 536 / 25 . 3 Chem . , 2009 , 395 : 1491 - 1502 . 2007 /0093462 A1 * 4 / 2007 Rogers . .. .. .. .. .. A61K 9 / 143 514 / 184 * cited by examiner U . S . Patent May1, 2018 Sheet 1 of 14 US 9, 958, 363 B2 Repeat1-4times CITI ? Moveto secondary extraction Vortex Spin FIG.1 14 : -??????A?? (1)2 U . S . Patent May 1 , 2018 Sheet 2 of 14 US 9 , 958 , 363 B2 4 Repeat1-4times Moveto secondary extraction FIG.2 Vortex Spin =-4-- (2) N-> U . S . Patent May 1, 2018 Sheet 3 of 14 US 9 , 958 , 363 B2 hings the balance bilan Ag®Agvb MAAAAAAAAAAA FIG . 3 U . S . Patent May 1 , 2018 Sheet 4 of 14 US 9 ,958 ,363 B2 Yeast cells Yeast cells 1000L water 500L water 50 UL HMIM - CI FIG . 4 U . S . Patent May 1, 2018 Sheet 5 of 14 US 9 , 958 , 363 B2 10% ? funt 30% EndogenousATPat60min YYYYYYYYYYYYYYYYYYYY 40% HMIM-CIaqueoussolutions 50% 70% (wn ) suopequeouos diV FIG.5 muleren ondoren Z ZZZZZZ .L€ U ZZIZIIDZZZZZZZZZZ CIHMIM-%ATPin80Endogenous EZZ77777777 RT Kagamanya ZZZZZZZZZZZZZZZZZZZZ f4bulanONUW062099OO funn y be - - - Jewe l d / morn www A ZZITIILIZOZITO w ÖLE : (wn ) uopejjuaquoo di U . S . Patent May 1 , 2018 Sheet 6 of 14 US 9 , 958 , 363 B2 Metabolism stays quenched using C18 column 00 230 min 2260 min Overnight Overnight2 ATPconcentration(UM) 0 .10 0 Dilute to 10 % (5X ) C18 Cleanup - 1 C18 Cleanup - 2 FIG . 6 U . S . Patent May 1 , 2018 Sheet 7 of 14 US 9 , 958 , 363 B2 womenin centerandfinit * * o 0.05101520253035404550556065707580859095 Countsvs.AcquisitionTime(min) FIG.7A . writualesdeinteresti wan wanne wwwww ini moment 0000 TOOTVO0010 NOQOTOQOTNOOT VOOTVO COCOOOOOLLOW NOON U . S . 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