title: Capillary Array Waveguide Amplified Fluorescence Detector for mHealth.
abstract: Mobile Health (mHealth) analytical technologies are potentially useful for carrying out modern medical diagnostics in resource-poor settings. Effective mHealth devices for underserved populations need to be simple, low cost, and portable. Although cell phone cameras have been used for biodetection, their sensitivity is a limiting factor because currently it is too low to be effective for many mHealth applications, which depend on detection of weak fluorescent signals. To improve the sensitivity of portable phones, a capillary tube array was developed to amplify fluorescence signals using their waveguide properties. An array configured with 36 capillary tubes was demonstrated to have a ~100X increase in sensitivity, lowering the limit of detection (LOD) of mobile phones from 1000 nM to 10 nM for fluorescein. To confirm that the amplification was due to waveguide behavior, we coated the external surfaces of the capillaries with silver. The silver coating interfered with the waveguide behavior and diminished the fluorescence signal, thereby proving that the waveguide behavior was the main mechanism for enhancing optical sensitivity. The optical configuration described here is novel in several ways. First, the use of capillaries waveguide properties to improve detection of weak florescence signal is new. Second we describe here a three dimensional illumination system, while conventional angular laser waveguide illumination is spot (or line), which is functionally one-dimensional illumination, can illuminate only a single capillary or a single column (when a line generator is used) of capillaries and thus inherently limits the multiplexing capability of detection. The planar illumination demonstrated in this work enables illumination of a two dimensional capillary array (e.g. x columns and y rows of capillaries). In addition, the waveguide light propagationviathe capillary wall provides a third dimension for illumination along the axis of the capillaries. Such an array can potentially be used for sensitive analysis of multiple fluorescent detection assays simultaneously. The simple phone based capillary array approach presented in this paper is capable of amplifying weak fluorescent signals thereby improving the sensitivity of optical detectors based on mobile phones. This may allow sensitive biological assays to be measured with low sensitivity detectors and may make mHealth practical for many diagnostics applications, especially in resource-poor and global health settings.
authors.affiliation: Division of Biology, Office of Science and Engineering, FDA, Silver Spring, MD 20993 ; University of Maryland, College Park, MD 20742.
authors.forename: Joshua
authors.initials: J
authors.lastname: Balsam
authors.forename: Hugh Alan
authors.initials: HA
authors.lastname: Bruck
authors.forename: Avraham
authors.initials: A
authors.lastname: Rasooly
keywords: CMOS; fluorescence; microfabrication; microfluidics; mobile phone; smartphone
references.citation: Lab Chip. 2012 Apr 21;12(8):1454-62
references.pmid: 22374412
references.citation: Biosens Bioelectron. 2011 Aug 15;26(12):4708-14
references.pmid: 21676608
references.citation: Appl Environ Microbiol. 2004 Jan;70(1):152-8
references.pmid: 14711637
references.citation: Yale J Biol Med. 2012 Sep;85(3):425-7
references.pmid: 23012591
references.citation: Lab Chip. 2010 Jul 21;10(14):1787-92
references.pmid: 20445943
references.citation: Analyst. 2012 Nov 7;137(21):5011-7
references.pmid: 22973572
references.citation: Annu Rev Biomed Eng. 2008;10:107-44
references.pmid: 18358075
references.citation: Anal Chem. 1999 Sep 1;71(17):3846-52
references.pmid: 10489530
references.citation: Anal Bioanal Chem. 2003 Oct;377(3):469-77
references.pmid: 12811462
references.citation: Lab Chip. 2011 Aug 21;11(16):2725-30
references.pmid: 21725557
references.citation: Lab Chip. 2009 Nov 21;9(22):3275-81
references.pmid: 19865736
references.citation: Methods Mol Biol. 2009;503:259-72
references.pmid: 19151946
references.citation: J Food Prot. 2003 Oct;66(10):1851-6
references.pmid: 14572223
references.citation: Sens Actuators B Chem. 2012;171-172:141-147
references.pmid: 23990697
references.citation: BMC Cardiovasc Disord. 2011 May 31;11:26
references.pmid: 21624142
references.citation: Dermatology. 2011;223(3):244-50
references.pmid: 22095005
references.citation: Biosens Bioelectron. 2011 Jul 15;26(11):4349-54
references.pmid: 21621401
references.citation: Anal Chem. 2004 Jan 15;76(2):433-40
references.pmid: 14719894
references.citation: Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:6801-4
references.pmid: 22255900
references.citation: Sens Actuators B Chem. 2010 Apr 8;146(1-8):297-306
references.pmid: 20498728
references.citation: Anal Biochem. 2000 Dec 15;287(2):234-42
references.pmid: 11112269
references.citation: Anal Chem. 2002 Feb 1;74(3):713-9
references.pmid: 11838701
references.citation: Sens Actuators B Chem. 2011 Mar 31;153(1):176-181
references.pmid: 21503269
references.citation: Anal Chem. 1999 Oct 1;71(19):4344-52
references.pmid: 10517150
references.citation: Biosens Bioelectron. 2008 Dec 1;24(4):618-25
references.pmid: 18644709
references.citation: Infect Dis Clin North Am. 2011 Jun;25(2):385-98
references.pmid: 21628053
references.citation: Lab Chip. 2011 Oct 21;11(20):3411-8
references.pmid: 21881677
references.citation: Nature. 2006 Nov 23;444 Suppl 1:73-9
references.pmid: 17159896
references.citation: Microb Ecol. 2004 Feb;47(2):175-85
references.pmid: 14765282
references.citation: Analyst. 2012 Jun 7;137(11):2541-4
references.pmid: 22396952
references.citation: Biosens Bioelectron. 1998 Mar 1;13(3-4):407-15
references.pmid: 9642774
references.citation: J Biotechnol. 1994 Feb 14;32(2):127-38
references.pmid: 7764559
references.citation: Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:3180-3
references.pmid: 22255015
references.citation: Clin Chem. 1998 Sep;44(9):2036-43
references.pmid: 9733002
references.citation: Anal Chem. 2011 Sep 1;83(17):6641-7
references.pmid: 21774454
references.citation: Addict Sci Clin Pract. 2012 Jun 08;7:9
references.pmid: 23186301
references.citation: Stud Health Technol Inform. 2012;177:242-7
references.pmid: 22942062
references.citation: Anal Chem. 1996 Jul 1;68(13):2164-9
references.pmid: 21619301
references.citation: Nature. 2006 Nov 23;444 Suppl 1:1-2
references.pmid: 17159888
references.citation: Lab Chip. 2012 Aug 7;12(15):2678-86
references.pmid: 22596243
references.citation: IEEE Trans Inf Technol Biomed. 2004 Dec;8(4):405-14
references.pmid: 15615031
references.citation: Lab Chip. 2011 Mar 7;11(5):941-9
references.pmid: 21243150
references.citation: Anal Chem. 2001 Nov 15;73(22):5518-24
references.pmid: 11816582
references.citation: Biosens Bioelectron. 2002 Jan;17(1-2):95-103
references.pmid: 11742740
references.citation: Lab Chip. 2011 Jan 7;11(1):120-6
references.pmid: 21109898
references.citation: Pan Afr Med J. 2011;10:37
references.pmid: 22187619
references.citation: Biosens Bioelectron. 2005 Jun 15;20(12):2470-87
references.pmid: 15854820
references.citation: Anal Bioanal Chem. 2009 May;394(2):499-505
references.pmid: 19290511
references.citation: J Appl Microbiol. 2004;96(1):47-58
references.pmid: 14678158
references.citation: Lab Chip. 2010 Aug 21;10(16):2093-100
references.pmid: 20544092
references.citation: Biosens Bioelectron. 1998 Oct 1;13(7-8):825-30
references.pmid: 9828378
references.citation: Biosens Bioelectron. 2000 Jan;14(10-11):771-7
references.pmid: 10945451