US 20130260367A1 (19) United States (12) Patent Application Publication oo) Pub. No.: US 2013/0260367 Al Lowery, JR. et al. (43) Pub. Date: Oct. 3,2013 (54) NMR SYSTEMS AND METHODS FOR THE (86) PCTNo.: PCT/US11/56936 RAPID DETECTION OF ANALYTES § 371 (c)(1), (2), (4) Date: Jun. 20, 2013 Related U.S. Application Data (75) Inventors: Thomas Jay Lowery, JR., Belmont, MA (US); Mark John Audeh, Brighton, (60) Provisional application No. 61/414,141, filed onNov. 16, 2010, provisional application No. 61/418,465, MA (US); Matthew Blanco, Boston, filed on Dec. I, 2010, provisional application No. MA (US); James Franklin Chepin, 61/497,374, filed on Jun. 15,2011. Arlington, MA (US); Vasiliki Demas, Arlington, MA (US); Rahul Dhanda, (30) Foreign Application Priority Data Needham, MA (US); Marilyn Lee Fritzemeier, Lexington, MA (US); Isaac Oct. 22, 2010 (US) .................................... 12/910594 Koh, Arlington, MA (US); Sonia Publication Classification Kumar, Cambridge, MA (US); Lori (51) Int. Cl. Anne Neely, Reading, MA (US); Brian GOlN 33/543 (2006.01) Mozeleski, Knox, ME (US); Daniella C12Q1/70 (2006.01) Lynn Plourde, Arlington, MA (US); GOlN 33/94 (2006.01) Charles William Rittershaus, Malden, C12Q1/68 (2006.01) MA (US); Parris Wellman, Reading, (52) U.S. Cl. MA (US) CPC ........ GOlN33/54326 (2013.01); C12Q1/6825 (2013.01); C12Q1/70 (2013.01); GOlN 33/9493 (2013.01); C12Q1/6895 (2013.01) USPC . 435/5; 436/501; 435/7.1; 435/6.11; 435/7.4; (73) Assignee: T2 Biosystems, Inc., Lexington, MA 435/287.2; 422/69; 422/554 (US) (57) ABSTRACT (21) Appl. No.: 13/384,051 This invention features systems and methods for the detection of analytes, and their use in the treatment and diagnosis of (22) PCT Filed: Oct. 19, 2011 disease. Patent Application Publication Oct. 3, 2013 Sheet I of 57 US 2013/0260367 Al Figure I A 100 r 102 #v s? s/ I\ * * * I t * ttft f/ 55 H 5! StfSfSff. /H f tf/f /' * t S ft ft ff RF OSCtLlATOR VOLTAGE (SIGNAL) Patent Application Publication Oct. 3, 2013 Sheet 2 of 57 US 2013/0260367 Al Figure IB Patent Application Publication Oct. 3, 2013 Sheet 3 of 57 US 2013/0260367 Al Figure 2 FIG, 2D 2D FIG, 2E FIG. 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I ............. 400 I------------- *•-. f 300 j----------------- p 200 I---------------- "T 10o [■--------------- 0 i------------------- 0.01 0.1 I 10 Crea, mg/dL Figure 25 A 12 Oustmni* Assay edits 2 Dsfferssti Asttibooy fAspa-atfem of IAOl SUaopdssS’rm i -¾- (-'rrpiaetssso a iprodssriiosy SOO SOi> A I £ t<50 £ 200 ■y O A 0 ,SatSSsody iOOOBHO’aOost. sig/fssi Figure 25 B Cmaimme Asttibody Titratfeso with AACs’2-3- 4, Creafsdesiwstfmd particles SOO - SGO '*00 y MvtilKWSf k s d 14H03 &Cm,5A a ■500 I ^OO <&• 4QQ v ^ £ & iOf> :•$ StJ on ny1 * I $ tiVb <r<y 30f> (¾ & (iiJC'Oi C -)1 i riy {vg/tr$ Figure 25 C PatentApplicationPublication Oct. 3, 2013 Sheet 26 of 57 US 2013/0260367 Al Figure 26 Effect of gMAA Processing Method on T2 510 490 Ij 600 ............. 470 | - i 500 ! f ' X " ] « * » 450 400 ■■ 77T JL 430 XControI ; I 300 i—— — LiJ 410 w -S-Twist : X 200 \ ! 390 0 1 8 0 ° turn X 100 i ............... ............. i ................................... ............. .............. 370 ■■ Remove 5s ; X 0 - ........... i 350 0 3 0 4 0.4 0 5 0.6 [AB] ng/mL [AB] |ig/mL Patent Application Publication Oct. 3, 2013 Sheet 27 of 57 US 2013/0260367 Al Figure 27 Creatinine Competitive Assay - sbgMAA Processing 450 r ................. 400 -- 350 j-.................. 300 j------------- -X- I 250 I.................. N 200 h ................. 150 j-.................. 100 F -.............. 50 ------------- 0 : 0.01 0.1 1 10 [Creat] mg/d L Patent Application Publication Oct. 3, 2013 Sheet 28 of 57 US 2013/0260367 Al Figure 28 AntigeirPrtftem Conjugate Jm Free Analyte Antibody-coated Particle Patent Application Publication Oct. 3, 2013 Sheet 29 of 57 US 2013/0260367 Al Figure 29 Tacrolimus Competitive Assay, Extracted Whole Blood • 5 PL Curve Fit Data 7 0 0 f I ■ 6 0 0 I- ...........