THOUTUS009810658B2 LIMUNUITUR (12 ) United States Patent ( 10 ) Patent No. : US 9 ,810 ,658 B2 Crooks et al. (45 ) Date of Patent: Nov . 7 , 2017 (54 ) METHOD FOR THE DETECTION AND 1 / 001 (2013 .01 ); C12Q 1 /6813 ( 2013. 01 ) ; QUANTIFICATION OF ANALYTES USING GOIN 33/ 5438 ( 2013 .01 ) ; GOIN 33 / 54373 THREE - DIMENSIONAL PAPER -BASED (2013 . 01 ) ; DEVICES (Continued ) (58 ) Field of Classification Search (71 ) Applicant: Board of Regents , The University of None Texas System , Austin , TX (US ) See application file for complete search history . ( 72 ) Inventors : Richard M . Crooks , College Station , TX (US ) ; Hong Liu , Nanjing (CN ) ; ( 56 ) References Cited Karen Scida , Austin , TX (US ) ; Christophe Renault , Austin , TX (US ) U . S . PATENT DOCUMENTS 2007/ 0000776 AL 1 / 2007 Karube et al. (73 ) Assignee : Board of Regents , The University of 2008 /0019866 AL 1 / 2008 Paek et al. Texas System , Austin , TX (US ) ( Continued ) ( * ) Notice : Subject to any disclaimer , the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 U . S . C . 154 ( b ) by 1192 days . KR 20110028019 3 / 2011 ( 21 ) Appl. No. : 13/ 865 , 352 OTHER PUBLICATIONS Liu et al. , Three - Dimensional Paper Microfluidic Devices ( 22 ) Filed : Apr. 18 , 2013 Assembled Using the Principles of Origami, Journal of the Ameri (65 ) Prior Publication Data can Chemical Society , 133 (44 ) , pp . 17564 - 17566 , published online Oct. 17 , 2011. * US 2015 /0355132 A1 Dec . 10 , 2015 (Continued ) Related U . S . Application Data Primary Examiner — Rebecca Martinez (60 ) Provisional application No . 61 /635 ,081 , filed on Apr. (74 ) Attorney , Agent, or Firm — Meunier Carlin & 18 , 2012 , provisional application No . 61 /641 , 880 , Curfman LLC ( Continued ) (57 ) ABSTRACT ( 51 ) Int. Ci. Described herein are three- dimensional ( 3 - D ) paper fluidic BOIL 3 / 00 ( 2006 . 01 ) devices. The entire 3 - D device is fabricated on a support GOIN 27 / 327 ( 2006 .01 ) layer formed from a single sheet of material and assembled ( Continued ) by folding the support layer . The folded structure may be ( 52 ) U . S . CI. enclosed in an impermeable cover or package . Chemically (52 ) UPC CPC .. GOIN 27 /3276 (2013 .01 ) ; BOIL 3 /5023 sensitive particles may be disposed in the support layer for ( 2013 . 01 ) ; BOIL 3 / 50273 ( 2013 .01 ) ; BOIL use in detecting analytes . 3 /502707 ( 2013 .01 ) ; BOIL 3 /502715 ( 20132013 .01 0315027011 ) ; BOIL 37502 3 /502738 ( 2013 .01 ) ; C12Q 19 Claims, 16 Drawing Sheets US 9 ,810 ,658 B2 Page 2 Related U . S . Application Data Schilling et al . “ Fully Enclosed Microfluidic Paper -Based Analyti cal Devices ” Anal . Chem . , 2012 , 84 ( 3 ), pp . 1579 - 1585 . filed on May 2 , 2012 , provisional application No . Kartalov et al. “ Microfluidic vias enable nested bioarrays and 61/ 756 ,772 , filed on Jan . 25 , 2013 . autoregulatory devices in Newtonian fluids” PNAS (2006 ) 103: 33 , 12280 - 12284 . (51 ) Int. CI. Martinez et al. “ Three - dimensional microfluidic devices fabricated GOIN 33 / 543 ( 2006 .01 ) in layered paper and tape” PNAS (2008 ) 105 :50 , 19606 - 19611 . c120 1 / 00 ( 2006 . 01 ) Martinez et al . “ Patterned Paper as a Platform for Inexpensive , Low C120 1 /68 ( 2006 . 01 ) Volume, Portable Bioassays” Angew Chem Int Ed Engl. 2007 ; GOIN 35 / 00 ( 2006 . 01 ) 46 ( 8 ) : 1318 - 1320 . GOIN 33 /487 (2006 .01 ) Marinez et al . “ FLASH : A rapid method for prototyping paper based microfluidic devices" Lab Chip . Dec . 2008 ; 8 ( 12 ) : 2146 (52 ) U . S . CI. 2150 . CPC .. BOIL 3 /5055 (2013 .01 ) ; BOIL 2200 / 12 Cheng et al. “ Paper - Based ELISA ” Angew Chem Int Ed Engl . ( 2013 .01 ) ; BOIL 2300 / 045 ( 2013 .01 ) ; BOIL 49 : 28 , pp . 4771- 4774 , 2010 . 2300 / 0627 ( 2013 .01 ) ; BOIL 2300 /0645 International Preliminary Report on Patentability for PCT Applica ( 2013 . 01 ) ; BOIL 2300 /0816 ( 2013 .01 ) ; BOIL tion No. PCT/ US2013 /037082 issued Oct. 21, 2014 . 2300 /0877 ( 2013 .01 ) ; BOIL 2300 / 126 Dungchai et al . “ Electrochemical Detection for Paper - Based ( 2013 .01 ) ; BOIL 2400 /0406 ( 2013 .01 ) ; BOIL Microfluidics” Anal. Chem . 2009 , 81, 5821- 5826 . 2400 /065 (2013 .01 ) ; GOIN 33 / 48707 Lu et al. “ Rapid prototyping of paper - based microfluidics with wax for low -cost , portable bioassay " Electrophoresis ( 2009 ) 30 : 1497 ( 2013 .01 ) ; GOIN 2035 / 00158 ( 2013 . 01 ) ; Y1OT 1500 . 29 /49984 ( 2015 .01 ) Osborn et al. “ Microfluidics without pumps: reinventing the T - sen sor and H - filter in paper networks ” Lab Chip , 2010 , 10 , 2659 -2665 . ( 56 ) References Cited Nie et al . “ Integration of paper -based microfluidic devices with commercial electrochemical readers " Lab Chip . Nov . 21, 2010 ; U . S . PATENT DOCUMENTS 10 (22 ) : 3163 - 3169 . Martinez et al . “ Diagnostics for the Developing World : Microfluidic 2011/ 0111517 A1 * 5 / 2011 Siegel . .. .. B01L 3 /502707 Paper - Based Analytical Devices” Anal. Chem . 2010 , 82 , 3 - 10 . 436 / 164 Martinez et al. “ Programmable diagnostic devices made from paper 2011/ 0123398 AL 5 /2011 Carrilho et al. and tape” Lab Chip , 2010 , 10 , 2499 - 2504 . Siegel et al. “ Foldable Printed Circuit Boards on Paper Substrates” OTHER PUBLICATIONS Adv . Funct . Mater . 2010 , 20 , 28 -35 . Xiang et al. “Using personal glucose meters and functional DNA Govindarajan et al ., A low cost point - of - care viscous sample prepa sensors to quantify a variety of analytical targets ” Nature Chemistry ration device for molecular diagnosis in the developing world ; an 3 , 697 - 703 . example of microfluidic origami, Lab Chip , 12 , pp . 174 - 181 , Carrilho et al. “ Understanding Wax Printing : A Simple Micropat published on Nov . 8 , 2011. * terning Process for Paper - Based Microfluidics ” Anal . Chem . 2009 , Fenton et al . “ Multiplex Lateral- Flow Test Strips Fabricated by 81 , 7091 - 7095 . Two - Dimensional Shaping " ACS Appl. Mater . Interfaces , 2009 , 1 International Search Report /Written Opinion for PCT Application ( 1 ) , 124 - 129 . No . PCT /US2013 /037082 issued Aug . 12 , 2013 . Unger et al . “ Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography ” Science 2000 288 : 113 . * cited by examiner U . S . Patent Nov . 7 , 2017 Sheet 1 of16 US 9, 810 , 658 B2 ??????? ?????? | ????? FIG . 1 .… ., FIG. 2 U . S . Patent Nov . 7 , 2017 Sheet 2 of 16 US 9 , 810 .658 B2 ? ATTA - ALL_ ????? ??????? ???. ” … … ???*-restattact.Eversitestests FIG . 3 atent Nov . 7 , 2017 Sheet 3 of 16 US 9 ,810 ,658 B2 glucose. : : : : : :Cotos : : : : : : . .. en. els. OnSetelah mencie FIG . 4 2005 MeanIntensity WMWM 23 Concentration: . : : : : : : :: : : : : . (uM FIG . 5 U . S . Patent Nov . 7, 2017 Sheet 4 of 16 US 9 ,810 ,658 B2 adenosineI FIG . 6A O mM adenosine 5 mM adenosine 6 mm FIG . 6B U . S . Patent Nov . 7, 2017 Sheet 5 of 16 US 9 ,810 ,658 B2 150 o ns o tushintensidigest 22 4 6 adenosine MM FIG . 6C Folding Lamination 17:4,;1 Sample loading Multimeter Capacitor ???????? FIG . 7 U . S . Patent Nov . 7 , 2017 Sheet 6 of 16 US 9 .810 , 658 B2 FIG . 8A FIG . BB U. S. Patentatent NovNov . 7 , 2017 SheeSheet 7 of 16 US 9 ,810 ,658 B2 soor ernoor1000000 . FIG . 9A : te FIG . 9B atent Nov . 7 , 2017 Sheet 8 of 16 US 9 ,810 ,658 B2 SGOX ODNA SGOXIDDNA 1 : 1 1st filtrate 3rd filtrate retentate Absorbance 0. 04 N I - I - II- I - J - I - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 -V 1 LLLLLLLL wwwwwwwwwwwwww bonbonitinhonhoitoaineen* 5555555555555 historike . 250 300 350 400 450 500 Wavelength (nm ) FIG . 10 www with capacitor w without capacitor Current(UA) 0 50 100 150 200 250 adenosine (UM ) FIG . 11 U . S . Patent Nov . 7, 2017 Sheet 9 of 16 US 9 ,810 , 658 B2 Antibody Present Antibody Not Present + A Mix 2° Ab /Gox with - ? sample= 0 Mix with supported î meAntigen that OCHO 8+ 8 Separate beads from 1 =liquids C ou = 2° Antibody / Glucose Oxidase (* 2°Ab /GOX " ) A = 90 Antibody (* 10AB " ) = Particle with support Antigen FIG . 1212 U . S . Patent Nov . 7, 2017 Sheet 10 of 16 US 9 ,810 ,658 B2 Antibody Present Antibody Not Present Sample contacts supported antigen 400-HO -100% Mixner wahwith PANDO2°Ab /GO 8: 8 Separate liquid from 100 1 separatebeads ligue trom No GOX Y = 2º Antibody /Glucose Oxidase (" 2ºAb/ GOx " ) A = 1º Antibody (* 1°AB " ) = Particle with support Antigen FIG . 13 atent Nov . 7 , 2017 Sheet 11 of 16 US 9 ,810 ,658 B2 Fepete ( CNi Fe( CN ), " Glucose ES * * * FIG . 14 U . S . 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