Abstract
Multiplex immunoassays (IAs) refer to IA formats that can simultaneously determine many analytes in a single sample. They are becoming critically important in healthcare for the diagnosis of complex diseases, which require the simultaneous monitoring of multiple disease biomarkers. The ongoing research efforts are based on the determination of clinical scores for such complex diseases by assigning appropriate weightages to various biomarkers based on their contribution to the disease. Although a wide range of multiplex IA formats have been demonstrated by researchers with few of them commercialized successfully, there is still a need for the development of advanced and bioanalytically superior multiplex IA formats that are clinically and commercially viable. Further, the multiplex IAs should align well with the established and clinically accredited IAs. We provide here an overview of various multiplex IA formats and technologies together with the challenges involved, prospects, and guided insights.
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References
Jung W, Han J, Choi J-W, Ahn CH. Point-of-care testing (POCT) diagnostic systems using microfluidic lab-on-a-chip technologies. Microelectron Eng. 2015;132:46–57.
Spindel S, Sapsford K. Evaluation of optical detection platforms for multiplexed detection of proteins and the need for point-of-care biosensors for clinical use. Sensors. 2014;14(12):22313–41.
Luppa PB, Bietenbeck A, Beaudoin C, Giannetti A. Clinically relevant analytical techniques, organizational concepts for application and future perspectives of point-of-care testing. Biotechnol Adv. 2016;34(3):139–60.
Vashist SK, Schneider EM, Luong JHT. Commercial smartphone-based devices and smart applications for personalized healthcare monitoring and management. Diagnostics. 2014;4(3):104–28.
Peacock PM, Zhang WJ, Trimpin S. Advances in ionization for mass spectrometry. Anal Chem. 2017;89(1):372–88.
Vashist SK, Luppa PB, Yeo LY, Ozcan A, Luong JHT. Emerging technologies for next-generation point-of-care testing. Trends Biotechnol. 2015;33(11):692–705.
Gauglitz G. Point-of-care platforms. Annu Rev Anal Chem. 2014;7:297–315.
Vashist SK, Mudanyali O, Schneider EM, Zengerle R, Ozcan A. Cellphone-based devices for bioanalytical sciences. Anal Bioanal Chem. 2014;406(14):3263–77.
Araz MK, Tentori AM, Herr AE. Microfluidic multiplexing in bioanalyses. J Lab Autom. 2013;18(5):350–66.
Gordon J, Michel G. Discerning trends in multiplex immunoassay technology with potential for resource-limited settings. Clin Chem. 2012;58(4):690–8.
Chin CD, Linder V, Sia SK. Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip. 2012;12(12):2118–34.
Rusling JF. Multiplexed electrochemical protein detection and translation to personalized cancer diagnostics. Anal Chem. 2013;85(11):5304–10.
Dunbar SA. Applications of Luminex® xMAP™ technology for rapid, high-throughput multiplexed nucleic acid detection. Clin Chim Acta. 2006;363(1):71–82.
Skogstrand K, Thorsen P, Norgaard-Pedersen B, Schendel DE, Sorensen LC, Hougaard DM. Simultaneous measurement of 25 inflammatory markers and neurotrophins in neonatal dried blood spots by immunoassay with xMAP technology. Clin Chem. 2005;51(10):1854–66.
Kofoed K, Schneider UV, Scheel T, Andersen O, Eugen-Olsen J. Development and validation of a multiplex add-on assay for sepsis biomarkers using xMAP technology. Clin Chem. 2006;52(7):1284–93.
Braeckmans K, De Smedt SC, Leblans M, Pauwels R, Demeester J. Encoding microcarriers: present and future technologies. Nat Rev Drug Discov. 2002;1(6):447–56.
Ateya DA, Erickson JS, Howell PB Jr, Hilliard LR, Golden JP, Ligler FS. The good, the bad, and the tiny: a review of microflow cytometry. Anal Bioanal Chem. 2008;391(5):1485–98.
Godin J, Chen CH, Cho SH, Qiao W, Tsai F, Lo YH. Microfluidics and photonics for bio-system-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip. J Biophotonics. 2008;1(5):355–76.
MSD Technology Platform. 2017. https://www.mesoscale.com/~/media/files/brochures/techbrochure.pdf
Chowdhury F, Williams A, Johnson P. Validation and comparison of two multiplex technologies, Luminex® and Mesoscale discovery, for human cytokine profiling. J Immunol Methods. 2009;340(1):55–64.
Fu Q, Zhu J, Van Eyk JE. Comparison of multiplex immunoassay platforms. Clin Chem. 2010;56(2):314–8.
Breen EC, Reynolds SM, Cox C, Jacobson LP, Magpantay L, Mulder CB, et al. Multisite comparison of high-sensitivity multiplex cytokine assays. Clin Vaccine Immunol. 2011;18(8):1229–42.
The EUROLINE: a new technique for extensive antibody profiles. 2017. https://www.euroimmun.com/products/techniken/euroline/euroline-beschreibung.html
EUROLineScan. 2017. https://www.euroimmun.com/products/produkte-geraete-software/automatisierung-software/eurolinescan.html
Triage. 2018. https://www.quidel.com/immunoassays/triage-test-kits
Clark TJ, McPherson PH, Buechler KF. The triage cardiac panel: cardiac markers for the triage system. Point of Care. 2002;1(1):42–6.
sciFLEXARRAYER. 2018. https://www.scienion.com/products/sciflexarrayers/.
sciREADER. 2018. https://www.scienion.com/products/scireaders/.
sciCONSUMABLEs. 2018. https://www.scienion.com/products/sciconsumables/.
Array. 2018. https://clinical.r-biopharm.com/technologies/array/.
Biochip immunoassays. 2018. https://www.randox.com/biochip-immunoassays/.
Multiplex testing. 2018. https://www.randox.com/multiplex-testing/.
Multiplex assays. 2018. https://www.biovendor.com/multiplex-assays
PictArrayâ„¢. 2018. https://www.pictordx.com/technology
Technology. 2018. https://www.genspeed-biotech.com/genspeed-biotech.com/technology/2/181/.
Gyrolab xPlore. 2018. http://www.gyros.com/products/systems/gyrolab-xplore/.
Gyrolab CDs. 2018. http://www.gyrosproteintechnologies.com/gyrolab-cds-automated-immunoassays
Piccolo Xpress. 2017. http://www.abaxis.com/medical/piccolo-xpress
Gorkin R, Park J, Siegrist J, Amasia M, Lee BS, Park JM, et al. Centrifugal microfluidics for biomedical applications. Lab Chip. 2010;10(14):1758–73.
Samsung LABGEO IB10. 2017. http://www.samsung.com/global/business/healthcare/healthcare/in-vitro-diagnostics/BCA-IB10/DE
Sackmann EK, Fulton AL, Beebe DJ. The present and future role of microfluidics in biomedical research. Nature. 2014;507(7491):181–9.
Robinson T, Dittrich PS. Microfluidic technology for molecular diagnostics. Adv Biochem Eng Biotechnol. 2013;133:89–114.
Feng LN, Bian ZP, Peng J, Jiang F, Yang GH, Zhu YD, et al. Ultrasensitive multianalyte electrochemical immunoassay based on metal ion functionalized titanium phosphate nanospheres. Anal Chem. 2012;84(18):7810–5.
Kong F-Y, Xu B-Y, Xu J-J, Chen HY. Simultaneous electrochemical immunoassay using CdS/DNA and PbS/DNA nanochains as labels. Biosens Bioelectron. 2012;39(1):177–82.
Wang J, Liu G, Merkoci A. Electrochemical coding technology for simultaneous detection of multiple DNA targets. J Am Chem Soc. 2003;125(11):3214–5.
Tang D, Hou L, Niessner R, Xu M, Gao Z, Knopp DJB, et al. Multiplexed electrochemical immunoassay of biomarkers using metal sulfide quantum dot nanolabels and trifunctionalized magnetic beads. Biosens Bioelectron. 2013;46:37–43.
Tang J, Tang D, Niessner R, Chen G, Knopp D. Magneto-controlled graphene immunosensing platform for simultaneous multiplexed electrochemical immunoassay using distinguishable signal tags. Anal Chem. 2011;83(13):5407–14.
Sato K, Yamanaka M, Takahashi H, Tokeshi M, Kimura H, Kitamori T. Microchip-based immunoassay system with branching multichannels for simultaneous determination of interferon-gamma. Electrophoresis. 2002;23(5):734–9.
Ko YJ, Maeng JH, Ahn Y, Hwang SY, Cho NG, Lee SH. Microchip-based multiplex electro-immunosensing system for the detection of cancer biomarkers. Electrophoresis. 2008;29(16):3466–76.
Shriver-Lake LC, Golden J, Bracaglia L, Ligler FS. Simultaneous assay for ten bacteria and toxins in spiked clinical samples using a microflow cytometer. Anal Bioanal Chem. 2013;405(16):5611–4.
Hashemi N, Erickson JS, Golden JP, Ligler FS. Optofluidic characterization of marine algae using a microflow cytometer. Biomicrofluidics. 2011;5(3):032009.
Vashist SK, Luong JHT. Handbook of immunoassay technologies: approaches, performances, and applications. London: Academic Press; 2018.
Li J, Macdonald J. Multiplexed lateral flow biosensors: technological advances for radically improving point-of-care diagnoses. Biosens Bioelectron. 2016;83:177–92.
Li J, Macdonald J. Multiplex lateral flow detection and binary encoding enables a molecular colorimetric 7-segment display. Lab Chip. 2016;16(2):242–5.
Song S, Liu N, Zhao Z, Njumbe Ediage E, Wu S, Sun C, et al. Multiplex lateral flow immunoassay for mycotoxin determination. Anal Chem. 2014;86(10):4995–5001.
Taranova N, Berlina A, Zherdev A, Dzantiev BJB. ‘Traffic light’immunochromatographic test based on multicolor quantum dots for the simultaneous detection of several antibiotics in milk. Biosens Bioelectron. 2015;63:255–61.
Lafleur LK, Bishop JD, Heiniger EK, Gallagher RP, Wheeler MD, Kauffman P, et al. A rapid, instrument-free, sample-to-result nucleic acid amplification test. Lab Chip. 2016;16(19):3777–87.
Mao X, Baloda M, Gurung AS, Lin Y, Liu G. Multiplex electrochemical immunoassay using gold nanoparticle probes and immunochromatographic strips. Electrochem Commun. 2008;10(10):1636–40.
Mao X, Wang W, Du T-E. Rapid quantitative immunochromatographic strip for multiple proteins test. Sens Actuators B: Chemical. 2013;186:315–20.
Triage MeterPro. 2018. https://www.quidel.com/immunoassays/triage-test-kits/triage-meterpro
Ahmed S, Bui MP, Abbas A. Paper-based chemical and biological sensors: engineering aspects. Biosens Bioelectron. 2016;77:249–63.
Rolland JP, Mourey DA. Paper as a novel material platform for devices. MRS Bull. 2013;38(4):299–305.
Yang Y, Noviana E, Nguyen MP, Geiss BJ, Dandy DS, Henry CS. Paper-based microfluidic devices: emerging themes and applications. Anal Chem. 2017;89(1):71–91.
Vella SJ, Beattie P, Cademartiri R, Laromaine A, Martinez AW, Phillips ST, et al. Measuring markers of liver function using a micropatterned paper device designed for blood from a fingerstick. Anal Chem. 2012;84(6):2883–91.
Pollock NR, Rolland JP, Kumar S, Beattie PD, Jain S, Noubary F, et al. A paper-based multiplexed transaminase test for low-cost, point-of-care liver function testing. Sci Transl Med. 2012;4(152):152ra29.
Dungchai W, Chailapakul O, Henry CS. Electrochemical detection for paper-based microfluidics. Anal Chem. 2009;81(14):5821–6.
Ge L, Yan J, Song X, Yan M, Ge S, Yu J. Three-dimensional paper-based electrochemiluminescence immunodevice for multiplexed measurement of biomarkers and point-of-care testing. Biomaterials. 2012;33(4):1024–31.
Li X, Liu X. A microfluidic paper-based origami nanobiosensor for label-free, ultrasensitive immunoassays. Adv Healthc Mater. 2016;5(11):1326–35.
Li W, Li L, Ge S, Song X, Ge L, Yan M, et al. Multiplex electrochemical origami immunodevice based on cuboid silver-paper electrode and metal ions tagged nanoporous silver–chitosan. Biosens Bioelectron. 2014;56:167–73.
Wu Y, Xue P, Hui KM, Kang Y. A paper-based microfluidic electrochemical immunodevice integrated with amplification-by-polymerization for the ultrasensitive multiplexed detection of cancer biomarkers. Biosens Bioelectron. 2014;52:180–7.
Wu Y, Xue P, Kang Y, Hui KM. Paper-based microfluidic electrochemical immunodevice integrated with nanobioprobes onto graphene film for ultrasensitive multiplexed detection of cancer biomarkers. Anal Chem. 2013;85(18):8661–8.
Zang D, Ge L, Yan M, Song X, Yu J. Electrochemical immunoassay on a 3D microfluidic paper-based device. Chem Commun. 2012;48(39):4683–5.
Vashist SK, Lam E, Hrapovic S, Male KB, Luong JHT. Immobilization of antibodies and enzymes on 3-aminopropyltriethoxysilane-functionalized bioanalytical platforms for biosensors and diagnostics. Chem Rev. 2014;114(21):11083–130.
Ling MM, Ricks C, Lea P. Multiplexing molecular diagnostics and immunoassays using emerging microarray technologies. Expert Rev Mol Diagn. 2007;7(1):87–98.
Chandra PE, Sokolove J, Hipp BG, Lindstrom TM, Elder JT, Reveille JD, et al. Novel multiplex technology for diagnostic characterization of rheumatoid arthritis. Arthritis Res Ther. 2011;13(3):R102.
Kadimisetty K, Malla S, Sardesai NP, Joshi AA, Faria RC, Lee NH, et al. Automated multiplexed ECL Immunoarrays for cancer biomarker proteins. Anal Chem. 2015;87(8):4472–8.
Chen P, Chung MT, McHugh W, Nidetz R, Li Y, Fu J, et al. Multiplex serum cytokine immunoassay using nanoplasmonic biosensor microarrays. ACS Nano. 2015;9(4):4173–81.
Masson JF. Surface plasmon resonance clinical biosensors for medical diagnostics. ACS Sens. 2017;2(1):16–30.
Acimovic SS, Ortega MA, Sanz V, Berthelot J, Garcia-Cordero JL, Renger J, et al. LSPR chip for parallel, rapid, and sensitive detection of cancer markers in serum. Nano Lett. 2014;14(5):2636–41.
Schumacher S, Nestler J, Otto T, Wegener M, Ehrentreich-Forster E, Michel D, et al. Highly-integrated lab-on-chip system for point-of-care multiparameter analysis. Lab Chip. 2012;12(3):464–73.
Otieno BA, Krause CE, Jones AL, Kremer RB, Rusling JF. Cancer diagnostics via ultrasensitive multiplexed detection of parathyroid hormone-related peptides with a microfluidic immunoarray. Anal Chem. 2016;88(18):9269–75.
Wilson MS, Nie W. Multiplex measurement of seven tumor markers using an electrochemical protein chip. Anal Chem. 2006;78(18):6476–83.
Wan Y, Su Y, Zhu X, Liu G, Fan C. Development of electrochemical immunosensors towards point of care diagnostics. Biosens Bioelectron. 2013;47:1–11.
DÃaz-González M, Muñoz-Berbel X, Jiménez-Jorquera C, Baldi A, Fernández-Sánchez C. Diagnostics using multiplexed electrochemical readout devices. Electroanalysis. 2014;26(6):1154–70.
Ghindilis AL, Smith MW, Schwarzkopf KR, Roth KM, Peyvan K, Munro SB, et al. CombiMatrix oligonucleotide arrays: genotyping and gene expression assays employing electrochemical detection. Biosens Bioelectron. 2007;22(9–10):1853–60.
Roth KM, Peyvan K, Schwarzkopf KR, Ghindilis A. Electrochemical detection of short DNA oligomer hybridization using the CombiMatrix ElectraSense microarray reader. Electroanalysis. 2006;18(19–20):1982–8.
Karle M, Vashist SK, Zengerle R, von Stetten F. Microfluidic solutions enabling continuous processing and monitoring of biological samples: a review. Anal Chim Acta. 2016;929:1–22.
Duncan PN, Ahrar S, Hui EE. Scaling of pneumatic digital logic circuits. Lab Chip. 2015;15(5):1360–5.
Araci IE, Brisk P. Recent developments in microfluidic large scale integration. Curr Opin Biotechnol. 2014;25:60–8.
Shao H, Chung J, Lee K, Balaj L, Min C, Carter BS, et al. Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat Commun. 2015;6:6999.
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(8):1015–9.
Lafleur L, Stevens D, McKenzie K, Ramachandran S, Spicar-Mihalic P, Singhal M, et al. Progress toward multiplexed sample-to-result detection in low resource settings using microfluidic immunoassay cards. Lab Chip. 2012;12(6):1119–27.
Kling A, Chatelle C, Armbrecht L, Qelibari E, Kieninger J, Dincer C, et al. Multianalyte antibiotic detection on an electrochemical microfluidic platform. Anal Chem. 2016;88(20):10036–43.
Vashist SK, Luong JHT. Bioanalytical requirements and regulatory guidelines for immunoassays. In: Handbook of immunoassay technologies. London: Elsevier; 2018. p. 81–95.
Vashist SK, Luong JHT. Trends in in vitro diagnostics and mobile healthcare. Biotechnol Adv. 2016;34(3):137–8.
Contreras-Naranjo JC, Wei Q, Ozcan A. Mobile phone-based microscopy, sensing, and diagnostics. IEEE J Sel Top Quantum Electron. 2016;22(3):1–14.
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Vashist, S.K. (2019). Multiplex Immunoassays. In: Point-of-Care Technologies Enabling Next-Generation Healthcare Monitoring and Management. Springer, Cham. https://doi.org/10.1007/978-3-030-11416-9_7
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