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Abstract
Background
In the search for more powerful tools for diagnoses of endemic diseases in resource-limited settings, we have been analyzing technologies with potential applicability. Increasingly, the process focuses on readily accessible bodily fluids combined with increasingly powerful multiplex capabilities to unambiguously diagnose a condition without resorting to reliance on a sophisticated reference laboratory. Although these technological advances may well have important implications for the sensitive and specific detection of disease, to date their clinical utility has not been demonstrated, especially in resource-limited settings. Furthermore, many emerging technological developments are in fields of physics or engineering, which are not readily available to or intelligible to clinicians or clinical laboratory scientists.
Content
This review provides a look at technology trends that could have applicability to high-sensitivity multiplexed immunoassays in resource-limited settings. Various technologies are explained and assessed according to potential for reaching relevant limits of cost, sensitivity, and multiplex capability. Frequently, such work is reported in technical journals not normally read by clinical scientists, and the authors make enthusiastic claims for the potential of their technology while ignoring potential pitfalls. Thus it is important to draw attention to technical hurdles that authors may not be publicizing.
Figures and Tables
Table 1
Summary of reports of immunoassays with detection limit information
aLimits of detection (LOD), converted to common unit of molarity from original, and rounded off to nearest integer. Values may be approximate and derived from the lowest value reported, not necessarily a complete statistical analysis. Determinations may be on pure substances in diluent with no information on sample matrix effects. Ranges are given for publications reporting more than 1 analyte; bNot always based on actual number of simultaneous analytes, but may be a potential value based on the number of sites available in the device; cSERS, surface-enhanced Raman spectroscopy; OWG, optical waveguide; EIA, enzyme immunoassay.
References
1. Hawkins KR, Weigl BH. Becker H, Wang W, editors. Microfluidic diagnostics for low-resource settings. Microfluidics, bioMEMs, and medical Microsystems VIII. 2010. Vol. 7593. Bellingham (WA): SPIE;75930L1–75930L15.
2. Patolsky F, Zheng GF, Hayden O, Lakadamyali M, Zhuang XW, Lieber CM. Electrical detection of single viruses. Proc Natl Acad Sci U S A. 2004. 101:14017–14022.
3. Gordon J, Michel G. Analytical sensitivity limits for lateral flow immunoassays. Clin Chem. 2008. 54:1250–1251.
4. Parpia ZA, Elghanian R, Nabatiyan A, Hardie DR, Kelso DM. P24 antigen rapid test for diagnosis of acute pediatric HIV infection. J Acquir Immune Defic Syndr. 2010. 55:413–419.
5. Leung WM, Chan CP, Leung MF, Renneberg R, Lehmann K, Renneberg I, et al. Novel "digitalstyle" rapid test simultaneously detecting heart attack and predicting cardiovascular disease risk. Anal Lett. 2005. 38:423–439.
6. Buechler KF, Moi S, Noar B, McGrath D, Villela J, Clancy M, et al. Simultaneous detection of 7 drugs of abuse by the Triage(tm) panel for drugs of abuse. Clin Chem. 1992. 38:1678–1684.
7. Buechler KF, McPherson P, Anderberg J, Lesefko S, Nakamura K, Briggs J, et al. Triage (r) point of care quantitative immunoassay system. J Clin Ligand Assay. 1999. 22:208–213.
8. Biosite triage TOX drug screen [product insert]. 2007.
9. Hong JW, Chung KH, Yoon HC. Fluorescence affinity sensing by using a self-contained fluid manoeuvring microfluidic chip. Analyst. 2008. 133:499.
10. Sia SK, Linder V, Parviz BA, Siegel A, Whitesides GM. An integrated approach to a portable and low-cost immunoassay for resource-poor settings. Angew Chem Int Ed Engl. 2004. 43:498–502.
11. Chin CD, Laksanasopin T, Cheung YK, Steinmiller D, Linder V, Parsa H, et al. Microfluidics-based diagnostics of infectious diseases in the developing world. Nat Med. 2011. 17:1015–1019.
12.
S Ching
J Gordon
ME McMahon
. Abbott Laboratories. Chromatographic test strips for determining ligands or receptors. US patent. 4,960,691. 1990. 10. 02.
13. Fu EL, Ramsey S, Kauffman P, Lutz B, Yager P. Transport in two-dimensional paper networks. Microfluid Nanofluidics. 2011. 10:29–35.
14. Martinez AW, Phillips ST, Whitesides GM. Threedimensional microfluidic devices fabricated in layered paper and tape. Proc Natl Acad Sci U S A. 2008. 105:19606–19611.
15. Melin J, Rundstrom G, Peterson C, Bakker J, MacCraith BD, Read M, et al. A multiplexed point-of-care assay for C-reactive protein and N-terminal pro-brain natriuretic peptide. Anal Biochem. 2011. 409:7–13.
16. Doering WE, Piotti ME, Natan MJ, Freeman RG. Sers as a foundation for nanoscale, optically detected biological labels. Adv Mater. 2007. 19:3100–3108.
17. Gopinath SCB. Biosensing applications of surface plasmon resonance-based biacore technology. Sens Actuators B Chem. 2010. 150:722–733.
18. Gauglitz G, Brecht A, Kraus G, Nahm W. Chem and biochemical sensors based on interferometry at thin (multi-)layers. Sens Actuators B Chem. 1993. 11:21–27.
19. Zavali M, Petrou PS, Goustouridis D, Raptis I, Misiakos K, Kakabakos SE. A regenerable flowthrough affinity sensor for label-free detection of proteins and DNA. J Chromatogr B Analyt Technol Biomed Life Sci. 2010. 878:237–242.
20. Zavali M, Petrou PS, Kakabakos SE, Kitsara M, Raptis I, Beltsios K, et al. Label-free kinetic study of biomolecular interactions by white light reflectance spectroscopy. Micro Nano Lett. 2006. 1:94–98.
21. Concepcion J, Witte K, Wartchow C, Choo S, Yao DF, Persson H, et al. Label-free detection of biomolecular interactions using biolayer interferometry for kinetic characterization. Comb Chem High Throughput Screen. 2009. 12:791–800.
22. Abdiche Y, Malashock D, Pinkerton A, Pons J. Determining kinetics and affinities of protein interactions using a parallel real-time label-free biosensor, the octet. Anal Biochem. 2008. 377:209–217.
23. Abdiche YN, Malashock DS, Pinkerton A, Pons J. Exploring blocking assays using octet, proteon, and biacore biosensors. Anal Biochem. 2009. 386:172–180.
24. Cleverley S, Chen I, Houle JF. Label-free and amplified quantitation of proteins in complex mixtures using diffractive optics technology. J Chromatogr B Analyt Technol Biomed Life Sci. 2010. 878:264–270.
25. Stimpson DI, Hoijer JV, Hsieh WT, Jou C, Gordon J, Theriault T, et al. Real-time detection of DNA hybridization and melting on oligonucleotide arrays by using optical-wave guides. Proc Natl Acad Sci U S A. 1995. 92:6379–6383.
26.
DI Stimpson
J Gordon
JV Hoijer
. Abbott Laboratories. Light scattering optical waveguide method for detecting specific binding events. US patent. 5599668. 1990. 09. 02.
27. Myatt CJ, Delaney M, Todorof K, Heil J, Givens M, Schooley RT, et al. Fauchet PM, editor. Low-cost, multiplexed biosensor for disease diagnosis. Frontiers in pathogen detection: from nanosensors to systems. 2009. Vol.7167. Bellingham (WA): SPIE;716703-1-9.
28. Bruls DM, Evers TH, Kahlman JAH, van Lankvelt PJW, Ovsyanko M, Pelssers EGM, et al. Rapid integrated biosensor for multiplexed immunoassays based on actuated magnetic nanoparticles. Lab Chip. 2009. 9:3504–3510.
29. Dittmer WU, Evers TH, Hardeman WM, Huijnen W, Kamps R, de Kievit P, et al. Rapid, high sensitivity, point-of-care test for cardiac troponin based on optomagnetic biosensor. Clin Chim Acta. 2010. 411:868–873.
30. Wang XF, Zhao M, Nolte DD. Prostate-specific antigen immunoassays on the BioCD. Anal Bioanal Chem. 2009. 393:1151–1156.
31. Wang XF, Zhao M, Nolte DD, Ratliff TL. Prostate specific antigen detection in patient sera by fluorescence-free BioCD protein array. Biosens Bioelectron. 2011. 26:1871–1875.
32. Zhao M, Wang XF, Lawrence GM, Espinoza P, Nolte DD. Molecular interferometric imaging for biosensor applications. IEEE J Sel Top Quantum Electron. 2007. 13:1680–1690.
33. Morais S, Carrascosa J, Mira D, Puchades R, Maquieira A. Microimmunoanalysis on standard compact discs to determine low abundant compounds. Anal Chem. 2007. 79:7628–7635.
34. Morais S, Tamarit-López J, Carrascosa J, Puchades R, Maquieira Á. Analytical prospect of compact disk technology in immunosensing. Anal Bioanal Chem. 2008. 391:2837–2844.
35. Tamarit-López J, Morais S, Puchades R, Maquieira A. Use of polystyrene spin-coated compact discs for microimmunoassaying. Anal Chim Acta. 2008. 609:120–130.
36. Morais S, Tortajada-Genaro LA, Arnandis-Chover T, Puchades R, Maquieira A. Multiplexed microimmunoassays on a digital versatile disk. Anal Chem. 2009. 81:5646–5654.
37. Tamarit-Lopez J, Morais S, Banuls MJ, Puchades R, Maquieira A. Development of hapten-linked microimmunoassays on polycarbonate discs. Anal Chem. 2010. 82:1954–1963.
38. Tamarit-Lopez J, Morais S, Puchades R, Maquieira A. Direct hapten-linked multiplexed immunoassays on polycarbonate surface. Biosens Bioelectron. 2011. 26:2694–2698.
39. Li YC, Ou LML, Yu HZ. Digitized molecular diagnostics: reading disk-based bioassays with standard computer drives. Anal Chem. 2008. 80:8216–8223.
40. Mastichiadis C, Niotis A, Petrou P, Kakabakos S, Misiakos K. Capillary-based immunoassays, immunosensors and DNA sensors: steps towards integration and multi-analysis. Trends Analyt Chem. 2008. 27:771–784.
41. Petrou PS, Kakabakos SE, Christofidis I, Argitis P, Misiakos K. Multi-analyte capillary immunosensor for the determination of hormones in human serum samples. Biosens Bioelectron. 2002. 17:261–268.
42. Niotis AE, Mastichiadis C, Petrou PS, Christofidis I, Kakabakos SE, Siafaka-Kapadai A, et al. Dual-cardiac marker capillary waveguide fluoroimmunosensor based on tyramide signal amplification. Anal Bioanal Chem. 2009. 396:1187–1196.
43. Misiakos K, Petrou PS, Kakabakos SE, Yannoukakos D, Contopanagos H, Knoll T, et al. Fully integrated monolithic optoelectronic transducer for real-time protein and DNA detection: the NEMOSLAB approach. Biosens Bioelectron. 2010. 26:1528–1535.
44. Petrou PS, Kakabakos SE, Misiakos K. Silicon optocouplers for biosensing. Int J Nanotechnol. 2009. 6:4–17.
45. Elsholz B, Wörl R, Blohm L, Albers J, Feucht H, Grunwald T, et al. Automated detection and quantitation of bacterial RNA by using electrical microarrays. Anal Chem. 2006. 78:4794–4802.
46. Quiel A, Jurgen B, Piechotta G, Le Foll AP, Ziebandt AK, Kohler C, et al. Electrical protein array chips for the detection of staphylococcal virulence factors. Appl Microbiol Biotechnol. 2010. 85:1619–1627.
47. Elsholz B, Nitsche A, Achenbach J, Ellerbrok H, Blohm L, Albers J, et al. Electrical microarrays for highly sensitive detection of multiplex PCR products from biological agents. Biosens Bioelectron. 2009. 24:1737–1743.
48. Lawi W, Wiita C, Snyder ST, Wei F, Wong D, Wong PK, et al. A microfluidic cartridge system for multiplexed clinical analysis. JALA. 2009. 14:407–412.
49. Liao JC, Mastali M, Gau V, Suchard MA, Moller AK, Bruckner DA, et al. Use of electrochemical DNA biosensors for rapid molecular identification of uropathogens in clinical urine specimens. J Clin Microbiol. 2006. 44:561–570.
50. Gau V, Wong D. Oral fluid nanosensor test (OFNASET) with advanced electrochemical-based molecular analysis platform. Ann N Y Acad Sci. 2007. 1098:401–410.
51. Apple FS, Murakami MM, Christenson RH, Campbell JL, Miller CJ, Hock KG, et al. Analytical performance of the i-STAT cardiac troponin I assay. Clin Chim Acta. 2004. 345:123–127.
52. Lee CS, Kim SK, Kim M. Ion-sensitive field-effect transistor for biological sensing. Sensors. 2009. 9:7111–7131.
53. Park HJ, Kim SK, Park K, Yil SY, Chung JW, Chung BH, et al. Monitoring of c-reactive protein using ion sensitive field effect transistor biosensor. Sens Lett. 2010. 8:233–237.
54. Bian C, Tong JH, Sun JZ, Zhang H, Xue QN, Xia SH. A field effect transistor (FET)-based immunosensor for detection of HbA1c and Hb. Biomed Microdevices. 2011. 13:345–352.
55. Zheng GF, Patolsky F, Cui Y, Wang WU, Lieber CM. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol. 2005. 23:1294–1301.
56. Gong JR. Label-free attomolar detection of proteins using integrated nanoelectronic and electrokinetic devices. Small. 2010. 6:967–973.
57. Patolsky F, Zheng GF, Lieber CM. Fabrication of silicon nanowire devices for ultrasensitive, labelfree, real-time detection of biological and chemical species. Nat Protoc. 2006. 1:1711–1724.
58. Gruner G. Carbon nanotube transistors for biosensing applications. Anal Bioanal Chem. 2006. 384:322–335.
59. Briman M, Artukovic E, Zhang L, Chia D, Goodglick L, Gruner G. Direct electronic detection of prostate-specific antigen in serum. Small. 2007. 3:758–762.
60. Stern E, Klemic JF, Routenberg DA, Wyrembak PN, Turner-Evans DB, Hamilton AD, et al. Labelfree immunodetection with CMOS-compatible semiconducting nanowires. Nature. 2007. 445:519–522.
61. Elfström N, Karlström AE, Linnros J. Silicon nanoribbons for electrical detection of biomolecules. Nano Lett. 2008. 8:945–949.
62. Chua JH, Chee RE, Agarwal A, Wong SM, Zhang GJ. Label-free electrical detection of cardiac biomarker with complementary metal-oxide semiconductor-compatible silicon nanowire sensor arrays. Anal Chem. 2009. 81:6266–6271.
63. Im HS, Huang XJ, Gu B, Choi YK. A dielectricmodulated field-effect transistor for biosensing. Nat Nanotechnol. 2007. 2:430–434.
64. Im M, Ahn JH, Han JW, Park TJ, Lee SY, Choi YK. Development of a point-of-care testing platform with a nanogap-embedded separated doublegate field effect transistor array and its readout system for detection of avian influenza. IEEE Sens J. 2011. 11:351–360.
65. Srinivasan B, Li Y, Jing Y, Xu Y, Yao X, Xing C, et al. A detection system based on giant magnetoresistive sensors and high-moment magnetic nanoparticles demonstrates zeptomole sensitivity: potential for personalized medicine. Angew Chem Int Ed Engl. 2009. 48:2764–2767.
66. Li YP, Srinivasan B, Jing Y, Yao XF, Hugger MA, Wang JP, et al. Nano-magnetic competition assay for low-abundance protein biomarker quantification in unprocessed human sera. J Am Chem Soc. 2010. 132:4388–4392.
67. Dittmer WU, de Kievit P, Prins MWJ, Vissers JLM, Mersch MEC, Martens M. Sensitive and rapid immunoassay for parathyroid hormone using magnetic particle labels and magnetic actuation. J Immunol Methods. 2008. 338:40–46.
68. Hall DA, Gaster RS, Lin T, Osterfeld SJ, Han S, Murmann B, et al. GMR biosensor arrays: a system perspective. Biosens Bioelectron. 2010. 25:2051–2057.
69. Hall DA, Gaster RS, Osterfeld SJ, Murmann B, Wang SX. GMR biosensor arrays: correction techniques for reproducibility and enhanced sensitivity. Biosens Bioelectron. 2010. 25:2177–2181.
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