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Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Review

Capillary nano-immunoassays: advancing quantitative proteomics analysis, biomarker assessment, and molecular diagnostics

Authors: Jin-Qiu Chen, Lalage M Wakefield, David J Goldstein

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

There is an emerging demand for the use of molecular profiling to facilitate biomarker identification and development, and to stratify patients for more efficient treatment decisions with reduced adverse effects. In the past decade, great strides have been made to advance genomic, transcriptomic and proteomic approaches to address these demands. While there has been much progress with these large scale approaches, profiling at the protein level still faces challenges due to limitations in clinical sample size, poor reproducibility, unreliable quantitation, and lack of assay robustness. A novel automated capillary nano-immunoassay (CNIA) technology has been developed. This technology offers precise and accurate measurement of proteins and their post-translational modifications using either charge-based or size-based separation formats. The system not only uses ultralow nanogram levels of protein but also allows multi-analyte analysis using a parallel single-analyte format for increased sensitivity and specificity. The high sensitivity and excellent reproducibility of this technology make it particularly powerful for analysis of clinical samples. Furthermore, the system can distinguish and detect specific protein post-translational modifications that conventional Western blot and other immunoassays cannot easily capture. This review will summarize and evaluate the latest progress to optimize the CNIA system for comprehensive, quantitative protein and signaling event characterization. It will also discuss how the technology has been successfully applied in both discovery research and clinical studies, for signaling pathway dissection, proteomic biomarker assessment, targeted treatment evaluation and quantitative proteomic analysis. Lastly, a comparison of this novel system with other conventional immuno-assay platforms is performed.
Literature
1.
go back to reference Miller I, Ashton-Chess J, Spolders H, Fert V, Ferrara J, Kroll W et al (2011) Market access challenges in the EU for high medical value diagnostic tests. Pers Med 8:137–148CrossRef Miller I, Ashton-Chess J, Spolders H, Fert V, Ferrara J, Kroll W et al (2011) Market access challenges in the EU for high medical value diagnostic tests. Pers Med 8:137–148CrossRef
2.
go back to reference Hudis CA (2007) Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med 357:39–51PubMedCrossRef Hudis CA (2007) Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med 357:39–51PubMedCrossRef
3.
4.
go back to reference Tan EH, Ramlau R, Pluzanska A, Kuo HP, Reck M, Milanowski J et al (2010) A multicentre phase II gene expression profiling study of putative relationships between tumour biomarkers and clinical response with erlotinib in non-small-cell lung cancer. Ann Oncol 21:217–222PubMedCentralPubMedCrossRef Tan EH, Ramlau R, Pluzanska A, Kuo HP, Reck M, Milanowski J et al (2010) A multicentre phase II gene expression profiling study of putative relationships between tumour biomarkers and clinical response with erlotinib in non-small-cell lung cancer. Ann Oncol 21:217–222PubMedCentralPubMedCrossRef
5.
go back to reference Guo NL, Wan YW, Tosun K, Lin H, Msiska Z, Flynn DC et al (2008) Confirmation of gene expression-based prediction of survival in non-small cell lung cancer. Clin Cancer Res 14:8213–8220PubMedCentralPubMedCrossRef Guo NL, Wan YW, Tosun K, Lin H, Msiska Z, Flynn DC et al (2008) Confirmation of gene expression-based prediction of survival in non-small cell lung cancer. Clin Cancer Res 14:8213–8220PubMedCentralPubMedCrossRef
6.
go back to reference Garman KS, Acharya CR, Edelman E, Grade M, Gaedcke J, Sud S et al (2008) A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities. Proc Natl Acad Sci USA 105:19432–19437PubMedCentralPubMedCrossRef Garman KS, Acharya CR, Edelman E, Grade M, Gaedcke J, Sud S et al (2008) A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities. Proc Natl Acad Sci USA 105:19432–19437PubMedCentralPubMedCrossRef
7.
go back to reference Hudson TJ, Anderson W, Artez A, Barker AD, Bell C, Bernabe RR et al (2010) International network of cancer genome projects. Nature 464:993–998PubMedCrossRef Hudson TJ, Anderson W, Artez A, Barker AD, Bell C, Bernabe RR et al (2010) International network of cancer genome projects. Nature 464:993–998PubMedCrossRef
8.
go back to reference Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892PubMedCrossRef Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892PubMedCrossRef
9.
go back to reference Din S, Lennon AM, Arnott ID, Hupp T, Satsangi J (2007) Technology insight: the application of proteomics in gastrointestinal disease. Nat Clin Pract Gastroenterol Hepatol 4:372–385PubMedCrossRef Din S, Lennon AM, Arnott ID, Hupp T, Satsangi J (2007) Technology insight: the application of proteomics in gastrointestinal disease. Nat Clin Pract Gastroenterol Hepatol 4:372–385PubMedCrossRef
11.
go back to reference HUPO (2010) A gene-centric human proteome project: HUPO–the human proteome organization. Mol Cell Proteomics 9:427–429CrossRef HUPO (2010) A gene-centric human proteome project: HUPO–the human proteome organization. Mol Cell Proteomics 9:427–429CrossRef
12.
go back to reference Gygi SP, Rochon Y, Franza BR, Aebersold R (1999) Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 19:1720–1730PubMedCentralPubMed Gygi SP, Rochon Y, Franza BR, Aebersold R (1999) Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 19:1720–1730PubMedCentralPubMed
13.
go back to reference Brennan DJ, O’Connor DP, Rexhepaj E, Ponten F, Gallagher WM (2010) Antibody-based proteomics: fast-tracking molecular diagnostics in oncology. Nat Rev Cancer 10:605–617PubMedCrossRef Brennan DJ, O’Connor DP, Rexhepaj E, Ponten F, Gallagher WM (2010) Antibody-based proteomics: fast-tracking molecular diagnostics in oncology. Nat Rev Cancer 10:605–617PubMedCrossRef
14.
go back to reference Kopf E, Zharhary D (2007) Antibody arrays—an emerging tool in cancer proteomics. Int J Biochem Cell Biol 39:1305–1317PubMedCrossRef Kopf E, Zharhary D (2007) Antibody arrays—an emerging tool in cancer proteomics. Int J Biochem Cell Biol 39:1305–1317PubMedCrossRef
15.
go back to reference VanMeter A, Signore M, Pierobon M, Espina V, Liotta LA, Petricoin EF 3rd (2007) Reverse-phase protein microarrays: application to biomarker discovery and translational medicine. Expert Rev Mol Diagn 7:625–633PubMedCrossRef VanMeter A, Signore M, Pierobon M, Espina V, Liotta LA, Petricoin EF 3rd (2007) Reverse-phase protein microarrays: application to biomarker discovery and translational medicine. Expert Rev Mol Diagn 7:625–633PubMedCrossRef
16.
17.
go back to reference Wulfkuhle JD, Edmiston KH, Liotta LA, Petricoin EF 3rd (2006) Technology insight: pharmacoproteomics for cancer–promises of patient-tailored medicine using protein microarrays. Nat Clin Pract Oncol 3:256–268PubMedCrossRef Wulfkuhle JD, Edmiston KH, Liotta LA, Petricoin EF 3rd (2006) Technology insight: pharmacoproteomics for cancer–promises of patient-tailored medicine using protein microarrays. Nat Clin Pract Oncol 3:256–268PubMedCrossRef
18.
go back to reference O’Neill RA, Bhamidipati A, Bi X, Deb-Basu D, Cahill L, Ferrante J et al (2006) Isoelectric focusing technology quantifies protein signaling in 25 cells. Proc Natl Acad Sci USA 103:16153–16158PubMedCentralPubMedCrossRef O’Neill RA, Bhamidipati A, Bi X, Deb-Basu D, Cahill L, Ferrante J et al (2006) Isoelectric focusing technology quantifies protein signaling in 25 cells. Proc Natl Acad Sci USA 103:16153–16158PubMedCentralPubMedCrossRef
19.
go back to reference Besong Agbo D, Klafki H, Poschmann G, Seyfarth K, Genius J, Janssen C et al (2013) Development of a capillary isoelectric focusing immunoassay to measure DJ-1 isoforms in biological samples. Anal Biochem 443:197–204PubMedCrossRef Besong Agbo D, Klafki H, Poschmann G, Seyfarth K, Genius J, Janssen C et al (2013) Development of a capillary isoelectric focusing immunoassay to measure DJ-1 isoforms in biological samples. Anal Biochem 443:197–204PubMedCrossRef
20.
go back to reference Chen JQ, Heldman MR, Herrmann MA, Kedei N, Woo W, Blumberg PM et al (2013) Absolute quantitation of endogenous proteins with precision and accuracy using a capillary Western system. Anal Biochem 442:97–103PubMedCentralPubMedCrossRef Chen JQ, Heldman MR, Herrmann MA, Kedei N, Woo W, Blumberg PM et al (2013) Absolute quantitation of endogenous proteins with precision and accuracy using a capillary Western system. Anal Biochem 442:97–103PubMedCentralPubMedCrossRef
21.
go back to reference Harding A (2013) Life science technologies: not your PI’s western blot. Science 339:1100–1102CrossRef Harding A (2013) Life science technologies: not your PI’s western blot. Science 339:1100–1102CrossRef
22.
go back to reference Fan AC, Deb-Basu D, Orban MW, Gotlib JR, Natkunam Y, O’Neill R et al (2009) Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens. Nat Med 15:566–571PubMedCentralPubMedCrossRef Fan AC, Deb-Basu D, Orban MW, Gotlib JR, Natkunam Y, O’Neill R et al (2009) Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens. Nat Med 15:566–571PubMedCentralPubMedCrossRef
23.
go back to reference Iacovides DC, Johnson AB, Wang N, Boddapati S, Korkola J, Gray JW (2013) Identification and quantification of AKT isoforms and phosphoforms in breast cancer using a novel nanofluidic immunoassay. Mol Cell Proteomics 12:3210–3220PubMedCentralPubMedCrossRef Iacovides DC, Johnson AB, Wang N, Boddapati S, Korkola J, Gray JW (2013) Identification and quantification of AKT isoforms and phosphoforms in breast cancer using a novel nanofluidic immunoassay. Mol Cell Proteomics 12:3210–3220PubMedCentralPubMedCrossRef
24.
go back to reference Klein BY, Tamir H, Hirschberg DL, Glickstein SB, Welch MG (2013) Oxytocin modulates mTORC1 pathway in the gut. Biochem Biophys Res Commun 432:466–471PubMedCentralPubMedCrossRef Klein BY, Tamir H, Hirschberg DL, Glickstein SB, Welch MG (2013) Oxytocin modulates mTORC1 pathway in the gut. Biochem Biophys Res Commun 432:466–471PubMedCentralPubMedCrossRef
25.
go back to reference Kedei N, Telek A, Czap A, Lubart ES, Czifra G, Yang D et al (2011) The synthetic bryostatin analog Merle 23 dissects distinct mechanisms of bryostatin activity in the LNCaP human prostate cancer cell line. Biochem Pharmacol 81:1296–1308PubMedCentralPubMedCrossRef Kedei N, Telek A, Czap A, Lubart ES, Czifra G, Yang D et al (2011) The synthetic bryostatin analog Merle 23 dissects distinct mechanisms of bryostatin activity in the LNCaP human prostate cancer cell line. Biochem Pharmacol 81:1296–1308PubMedCentralPubMedCrossRef
26.
go back to reference Klamer SE, Kuijk CGM, Hordijk PL, van der Schoot CE, von Lindern M, van Hennik PB et al (2013) BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells. Cell Adhes Migr 7:434–449CrossRef Klamer SE, Kuijk CGM, Hordijk PL, van der Schoot CE, von Lindern M, van Hennik PB et al (2013) BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells. Cell Adhes Migr 7:434–449CrossRef
27.
go back to reference Gonsalves CS, Crable S, Chandra S, Li W, Kalra VK, Joiner CH (2014) Angiogenic growth factors augment K-Cl cotransporter expression in erythroid cells via hypoxia-inducible factor-1alpha. Am J Hematol 89:273–281PubMedCentralPubMedCrossRef Gonsalves CS, Crable S, Chandra S, Li W, Kalra VK, Joiner CH (2014) Angiogenic growth factors augment K-Cl cotransporter expression in erythroid cells via hypoxia-inducible factor-1alpha. Am J Hematol 89:273–281PubMedCentralPubMedCrossRef
28.
go back to reference Gordillo GM, Biswas A, Khanna S, Pan X, Sinha M, Roy S et al (2014) Dicer knockdown inhibits endothelial cell tumor growth via microRNA 21a-3p targeting of Nox-4. J Biol Chem 289:9027–9038PubMedCentralPubMedCrossRef Gordillo GM, Biswas A, Khanna S, Pan X, Sinha M, Roy S et al (2014) Dicer knockdown inhibits endothelial cell tumor growth via microRNA 21a-3p targeting of Nox-4. J Biol Chem 289:9027–9038PubMedCentralPubMedCrossRef
29.
go back to reference Serrano M, Moreno M, Ortega FJ, Xifra G, Ricart W, Moreno-Navarrete JM et al (2014) Adipose tissue mu-crystallin is a thyroid hormone-binding protein associated with systemic insulin sensitivity. J Clin Endocrinol Metab 99:E2259–E2268PubMedCrossRef Serrano M, Moreno M, Ortega FJ, Xifra G, Ricart W, Moreno-Navarrete JM et al (2014) Adipose tissue mu-crystallin is a thyroid hormone-binding protein associated with systemic insulin sensitivity. J Clin Endocrinol Metab 99:E2259–E2268PubMedCrossRef
30.
go back to reference Price FD, von Maltzahn J, Bentzinger CF, Dumont NA, Yin H, Chang NC et al (2014) Inhibition of JAK-STAT signaling stimulates adult satellite cell function. Nat Med 20:1174–1181PubMedCentralPubMedCrossRef Price FD, von Maltzahn J, Bentzinger CF, Dumont NA, Yin H, Chang NC et al (2014) Inhibition of JAK-STAT signaling stimulates adult satellite cell function. Nat Med 20:1174–1181PubMedCentralPubMedCrossRef
31.
go back to reference Bakhsheshian J, Hall MD, Robey RW, Herrmann MA, Chen JQ, Bates SE et al (2013) Overlapping substrate and inhibitor specificity of human and murine ABCG2. Drug Metab Dispos 41:1805–1812PubMedCentralPubMedCrossRef Bakhsheshian J, Hall MD, Robey RW, Herrmann MA, Chen JQ, Bates SE et al (2013) Overlapping substrate and inhibitor specificity of human and murine ABCG2. Drug Metab Dispos 41:1805–1812PubMedCentralPubMedCrossRef
32.
go back to reference Choi YP, Lee JH, Gao MQ, Kim BG, Kang S, Kim SH et al (2014) Cancer-associated fibroblast promote transmigration through endothelial brain cells in three-dimensional in vitro models. Int J Cancer 135:2024–2033PubMedCrossRef Choi YP, Lee JH, Gao MQ, Kim BG, Kang S, Kim SH et al (2014) Cancer-associated fibroblast promote transmigration through endothelial brain cells in three-dimensional in vitro models. Int J Cancer 135:2024–2033PubMedCrossRef
33.
go back to reference Beccano-Kelly DA, Kuhlmann N, Tatarnikov I, Volta M, Munsie LN, Chou P et al (2014) Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice. Front Cell Neurosci 8:301PubMedCentralPubMedCrossRef Beccano-Kelly DA, Kuhlmann N, Tatarnikov I, Volta M, Munsie LN, Chou P et al (2014) Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice. Front Cell Neurosci 8:301PubMedCentralPubMedCrossRef
34.
go back to reference Daniels VW, Smans K, Royaux I, Chypre M, Swinnen JV, Zaidi N (2014) Cancer cells differentially activate and thrive on de novo lipid synthesis pathways in a low-lipid environment. PLoS One 9:e106913PubMedCentralPubMedCrossRef Daniels VW, Smans K, Royaux I, Chypre M, Swinnen JV, Zaidi N (2014) Cancer cells differentially activate and thrive on de novo lipid synthesis pathways in a low-lipid environment. PLoS One 9:e106913PubMedCentralPubMedCrossRef
35.
go back to reference Liu SB, Sardi S, Sonom B, Zocco D, McSweeney R, Fraser AD et al (2013) The application of a novel nanovolume capillary electrophoresis-based protein analysis system in personalized & translational medicine research. J Bioanal Biomed S3:004. doi:10.4172/1948-593X.S3-004 Liu SB, Sardi S, Sonom B, Zocco D, McSweeney R, Fraser AD et al (2013) The application of a novel nanovolume capillary electrophoresis-based protein analysis system in personalized & translational medicine research. J Bioanal Biomed S3:004. doi:10.​4172/​1948-593X.​S3-004
36.
go back to reference Kohn EA, Yang YA, Du Z, Nagano Y, Van Schyndle CM, Herrmann MA et al (2012) Biological responses to TGF-beta in the mammary epithelium show a complex dependency on Smad3 gene dosage with important implications for tumor progression. Mol Cancer Res 10:1389–1399PubMedCentralPubMedCrossRef Kohn EA, Yang YA, Du Z, Nagano Y, Van Schyndle CM, Herrmann MA et al (2012) Biological responses to TGF-beta in the mammary epithelium show a complex dependency on Smad3 gene dosage with important implications for tumor progression. Mol Cancer Res 10:1389–1399PubMedCentralPubMedCrossRef
37.
go back to reference Sabnis H, Bradley HL, Bunting ST, Cooper TM, Bunting KD (2014) Capillary nano-immunoassay for Akt 1/2/3 and 4EBP1 phosphorylation in acute myeloid leukemia. J Transl Med 12:166PubMedCentralPubMedCrossRef Sabnis H, Bradley HL, Bunting ST, Cooper TM, Bunting KD (2014) Capillary nano-immunoassay for Akt 1/2/3 and 4EBP1 phosphorylation in acute myeloid leukemia. J Transl Med 12:166PubMedCentralPubMedCrossRef
38.
go back to reference Kedei N, Lewin NE, Geczy T, Selezneva J, Braun DC, Chen J et al (2013) Biological profile of the less lipophilic and synthetically more accessible bryostatin 7 closely resembles that of bryostatin 1. ACS Chem Biol 8:767–777PubMedCentralPubMedCrossRef Kedei N, Lewin NE, Geczy T, Selezneva J, Braun DC, Chen J et al (2013) Biological profile of the less lipophilic and synthetically more accessible bryostatin 7 closely resembles that of bryostatin 1. ACS Chem Biol 8:767–777PubMedCentralPubMedCrossRef
39.
go back to reference DeChristopher BA, Fan AC, Felsher DW, Wender PA (2012) “Picolog,” a synthetically-available bryostatin analog, inhibits growth of MYC-induced lymphoma in vivo. Oncotarget 3:58–66PubMedCentralPubMed DeChristopher BA, Fan AC, Felsher DW, Wender PA (2012) “Picolog,” a synthetically-available bryostatin analog, inhibits growth of MYC-induced lymphoma in vivo. Oncotarget 3:58–66PubMedCentralPubMed
40.
go back to reference de Kreuk BJ, Anthony EC, Geerts D, Hordijk PL (2012) The F-BAR protein PACSIN2 regulates epidermal growth factor receptor internalization. J Biol Chem 287:43438–43453PubMedCentralPubMedCrossRef de Kreuk BJ, Anthony EC, Geerts D, Hordijk PL (2012) The F-BAR protein PACSIN2 regulates epidermal growth factor receptor internalization. J Biol Chem 287:43438–43453PubMedCentralPubMedCrossRef
41.
go back to reference Fiscus RR, Leung EL, Wong JC, Johlfs MG (2012) Nitric oxide/protein kinase GIα promotes c-Src activation, proliferation and chemoresistance in ovarian cancer. In Farghaly DS (ed) Ovarian Cancer—Basic Science Perspective. InTech, pp 315–334 Fiscus RR, Leung EL, Wong JC, Johlfs MG (2012) Nitric oxide/protein kinase GIα promotes c-Src activation, proliferation and chemoresistance in ovarian cancer. In Farghaly DS (ed) Ovarian Cancer—Basic Science Perspective. InTech, pp 315–334
42.
go back to reference Aspinall-O’Dea M, Pierce A, Pellicano F, Williamson AJ, Scott MT, Walker MJ et al (2015) Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines. Nat Protoc 10:149–168PubMedCrossRef Aspinall-O’Dea M, Pierce A, Pellicano F, Williamson AJ, Scott MT, Walker MJ et al (2015) Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines. Nat Protoc 10:149–168PubMedCrossRef
43.
go back to reference Eldridge S, Guo L, Mussio J, Furniss M, Hamre J 3rd, Davis M (2014) Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci 141:547–559PubMedCrossRef Eldridge S, Guo L, Mussio J, Furniss M, Hamre J 3rd, Davis M (2014) Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci 141:547–559PubMedCrossRef
44.
go back to reference Frogne T, Sylvestersen KB, Kubicek S, Nielsen ML, Hecksher-Sorensen J (2012) Pdx1 is post-translationally modified in vivo and serine 61 is the principal site of phosphorylation. PLoS One 7:e35233PubMedCentralPubMedCrossRef Frogne T, Sylvestersen KB, Kubicek S, Nielsen ML, Hecksher-Sorensen J (2012) Pdx1 is post-translationally modified in vivo and serine 61 is the principal site of phosphorylation. PLoS One 7:e35233PubMedCentralPubMedCrossRef
45.
go back to reference Huang CC, Weng JH, Wei TY, Wu PY, Hsu PH, Chen YH et al (2012) Intermolecular binding between TIFA-FHA and TIFA-pT mediates tumor necrosis factor alpha stimulation and NF-kappaB activation. Mol Cell Biol 32:2664–2673PubMedCentralPubMedCrossRef Huang CC, Weng JH, Wei TY, Wu PY, Hsu PH, Chen YH et al (2012) Intermolecular binding between TIFA-FHA and TIFA-pT mediates tumor necrosis factor alpha stimulation and NF-kappaB activation. Mol Cell Biol 32:2664–2673PubMedCentralPubMedCrossRef
46.
go back to reference Sun Z, Li X, Massena S, Kutschera S, Padhan N, Gualandi L et al (2012) VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd. J Exp Med 209:1363–1377PubMedCentralPubMedCrossRef Sun Z, Li X, Massena S, Kutschera S, Padhan N, Gualandi L et al (2012) VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd. J Exp Med 209:1363–1377PubMedCentralPubMedCrossRef
47.
go back to reference Guo H, Gao M, Lu Y, Liang J, Lorenzi PL, Bai S et al (2014) Coordinate phosphorylation of multiple residues on single AKT1 and AKT2 molecules. Oncogene 33:3463–3472PubMedCrossRef Guo H, Gao M, Lu Y, Liang J, Lorenzi PL, Bai S et al (2014) Coordinate phosphorylation of multiple residues on single AKT1 and AKT2 molecules. Oncogene 33:3463–3472PubMedCrossRef
48.
go back to reference Chen JQ, Lee JH, Herrmann MA, Park KS, Heldman MR, Goldsmith PK et al (2013) Capillary isoelectric-focusing immunoassays to study dynamic oncoprotein phosphorylation and drug response to targeted therapies in non-small cell lung cancer. Mol Cancer Ther 12:2601–2613PubMedCrossRef Chen JQ, Lee JH, Herrmann MA, Park KS, Heldman MR, Goldsmith PK et al (2013) Capillary isoelectric-focusing immunoassays to study dynamic oncoprotein phosphorylation and drug response to targeted therapies in non-small cell lung cancer. Mol Cancer Ther 12:2601–2613PubMedCrossRef
49.
go back to reference Icardi L, Mori R, Gesellchen V, Eyckerman S, De Cauwer L, Verhelst J et al (2012) The Sin3a repressor complex is a master regulator of STAT transcriptional activity. Proc Natl Acad Sci USA 109:12058–12063PubMedCentralPubMedCrossRef Icardi L, Mori R, Gesellchen V, Eyckerman S, De Cauwer L, Verhelst J et al (2012) The Sin3a repressor complex is a master regulator of STAT transcriptional activity. Proc Natl Acad Sci USA 109:12058–12063PubMedCentralPubMedCrossRef
50.
go back to reference Tikhanovich I, Kuravi S, Campbell RV, Kharbanda KK, Artigues A, Villar MT et al (2014) Regulation of FOXO3 by phosphorylation and methylation in hepatitis C virus infection and alcohol exposure. Hepatology 59:58–70PubMedCrossRef Tikhanovich I, Kuravi S, Campbell RV, Kharbanda KK, Artigues A, Villar MT et al (2014) Regulation of FOXO3 by phosphorylation and methylation in hepatitis C virus infection and alcohol exposure. Hepatology 59:58–70PubMedCrossRef
51.
go back to reference Seetharam M, Fan AC, Tran M, Xu L, Renschler JP, Felsher DW et al (2012) Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na. Leuk Res 36:98–103PubMedCentralPubMedCrossRef Seetharam M, Fan AC, Tran M, Xu L, Renschler JP, Felsher DW et al (2012) Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na. Leuk Res 36:98–103PubMedCentralPubMedCrossRef
52.
go back to reference Fan AC, O’Rourke JJ, Praharaj DR, Felsher DW (2013) Real-time nanoscale proteomic analysis of the novel multi-kinase pathway inhibitor rigosertib to measure the response to treatment of cancer. Expert Opin Investig Drugs 22:1495–1509PubMedCentralPubMedCrossRef Fan AC, O’Rourke JJ, Praharaj DR, Felsher DW (2013) Real-time nanoscale proteomic analysis of the novel multi-kinase pathway inhibitor rigosertib to measure the response to treatment of cancer. Expert Opin Investig Drugs 22:1495–1509PubMedCentralPubMedCrossRef
53.
go back to reference Hubbard MA, Khalil AA, Schoeff SS, Allak A, VanKoevering KK, Maxwell AK et al (2014) Nanoimmunoassay to detect responses in head and neck cancer: feasibility in a mouse model. Otolaryngol Head Neck Surg 151:92–99PubMedCrossRef Hubbard MA, Khalil AA, Schoeff SS, Allak A, VanKoevering KK, Maxwell AK et al (2014) Nanoimmunoassay to detect responses in head and neck cancer: feasibility in a mouse model. Otolaryngol Head Neck Surg 151:92–99PubMedCrossRef
54.
go back to reference Siggers P, Carre GA, Bogani D, Warr N, Wells S, Hilton H et al (2014) A novel mouse Fgfr2 mutant, hobbyhorse (hob), exhibits complete XY gonadal sex reversal. PLoS One 9:e100447PubMedCentralPubMedCrossRef Siggers P, Carre GA, Bogani D, Warr N, Wells S, Hilton H et al (2014) A novel mouse Fgfr2 mutant, hobbyhorse (hob), exhibits complete XY gonadal sex reversal. PLoS One 9:e100447PubMedCentralPubMedCrossRef
55.
go back to reference Drew DA, Devers T, Horelik N, Yang S, O’Brien M, Wu R et al (2013) Nanoproteomic analysis of extracellular receptor kinase-1/2 post-translational activation in microdissected human hyperplastic colon lesions. Proteomics 13:1428–1436PubMedCentralPubMedCrossRef Drew DA, Devers T, Horelik N, Yang S, O’Brien M, Wu R et al (2013) Nanoproteomic analysis of extracellular receptor kinase-1/2 post-translational activation in microdissected human hyperplastic colon lesions. Proteomics 13:1428–1436PubMedCentralPubMedCrossRef
56.
go back to reference Goff DJ, Recart AC, Sadarangani A, Chun HJ, Barrett CL, Krajewska M et al (2013) A pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition. Cell Stem Cell 12:316–328PubMedCentralPubMedCrossRef Goff DJ, Recart AC, Sadarangani A, Chun HJ, Barrett CL, Krajewska M et al (2013) A pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition. Cell Stem Cell 12:316–328PubMedCentralPubMedCrossRef
57.
go back to reference Xin HW, Ambe CM, Hari DM, Wiegand GW, Miller TC, Chen JQ et al (2013) Label-retaining liver cancer cells are relatively resistant to sorafenib. Gut 62:1777–1786PubMedCrossRef Xin HW, Ambe CM, Hari DM, Wiegand GW, Miller TC, Chen JQ et al (2013) Label-retaining liver cancer cells are relatively resistant to sorafenib. Gut 62:1777–1786PubMedCrossRef
58.
go back to reference Williamson AJ, Pierce A, Jaworska E, Zhou C, Aspinall-O’Dea M, Lancashire L et al (2013) A specific PTPRC/CD45 phosphorylation event governed by stem cell chemokine CXCL12 regulates primitive hematopoietic cell motility. Mol Cell Proteomics 12:3319–3329PubMedCentralPubMedCrossRef Williamson AJ, Pierce A, Jaworska E, Zhou C, Aspinall-O’Dea M, Lancashire L et al (2013) A specific PTPRC/CD45 phosphorylation event governed by stem cell chemokine CXCL12 regulates primitive hematopoietic cell motility. Mol Cell Proteomics 12:3319–3329PubMedCentralPubMedCrossRef
60.
go back to reference Kentsis A, Reed C, Rice KL, Sanda T, Rodig SJ, Tholouli E et al (2012) Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia. Nat Med 18:1118–1122PubMedCentralPubMedCrossRef Kentsis A, Reed C, Rice KL, Sanda T, Rodig SJ, Tholouli E et al (2012) Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia. Nat Med 18:1118–1122PubMedCentralPubMedCrossRef
61.
go back to reference Beurlet S, Omidvar N, Gorombei P, Krief P, Le Pogam C, Setterblad N et al (2013) BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of AML by targeting primitive LSK and progenitor cells. Blood 122:2864–2876PubMedCentralPubMedCrossRef Beurlet S, Omidvar N, Gorombei P, Krief P, Le Pogam C, Setterblad N et al (2013) BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of AML by targeting primitive LSK and progenitor cells. Blood 122:2864–2876PubMedCentralPubMedCrossRef
62.
go back to reference Michels DA, Tu AW, McElroy W, Voehringer D, Salas-Solano O (2012) Charge heterogeneity of monoclonal antibodies by multiplexed imaged capillary isoelectric focusing immunoassay with chemiluminescence detection. Anal Chem 84:5380–5386PubMedCrossRef Michels DA, Tu AW, McElroy W, Voehringer D, Salas-Solano O (2012) Charge heterogeneity of monoclonal antibodies by multiplexed imaged capillary isoelectric focusing immunoassay with chemiluminescence detection. Anal Chem 84:5380–5386PubMedCrossRef
63.
go back to reference Rustandi RR, Loughney JW, Hamm M, Hamm C, Lancaster C, Mach A et al (2012) Qualitative and quantitative evaluation of Simon, a new CE-based automated Western blot system as applied to vaccine development. Electrophoresis 33:2790–2797PubMedCrossRef Rustandi RR, Loughney JW, Hamm M, Hamm C, Lancaster C, Mach A et al (2012) Qualitative and quantitative evaluation of Simon, a new CE-based automated Western blot system as applied to vaccine development. Electrophoresis 33:2790–2797PubMedCrossRef
64.
go back to reference Loughney JW, Lancaster C, Ha S, Rustandi RR (2014) Residual bovine serum albumin (BSA) quantitation in vaccines using automated capillary western technology. Anal Biochem 461:49–56PubMedCrossRef Loughney JW, Lancaster C, Ha S, Rustandi RR (2014) Residual bovine serum albumin (BSA) quantitation in vaccines using automated capillary western technology. Anal Biochem 461:49–56PubMedCrossRef
65.
go back to reference Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L et al (2010) Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol 28:595–599PubMedCentralPubMedCrossRef Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L et al (2010) Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol 28:595–599PubMedCentralPubMedCrossRef
66.
go back to reference Leng SX, McElhaney JE, Walston JD, Xie D, Fedarko NS, Kuchel GA (2008) ELISA and multiplex technologies for cytokine measurement in inflammation and aging research. J Gerontol A Biol Sci Med Sci 63:879–884PubMedCentralPubMedCrossRef Leng SX, McElhaney JE, Walston JD, Xie D, Fedarko NS, Kuchel GA (2008) ELISA and multiplex technologies for cytokine measurement in inflammation and aging research. J Gerontol A Biol Sci Med Sci 63:879–884PubMedCentralPubMedCrossRef
67.
go back to reference Vignali DA (2000) Multiplexed particle-based flow cytometric assays. J Immunol Methods 243:243–255PubMedCrossRef Vignali DA (2000) Multiplexed particle-based flow cytometric assays. J Immunol Methods 243:243–255PubMedCrossRef
68.
go back to reference Hoheisel JD, Alhamdani MS, Schroder C (2013) Affinity-based microarrays for proteomic analysis of cancer tissues. Proteomics Clin Appl 7:8–15PubMedCrossRef Hoheisel JD, Alhamdani MS, Schroder C (2013) Affinity-based microarrays for proteomic analysis of cancer tissues. Proteomics Clin Appl 7:8–15PubMedCrossRef
69.
go back to reference Rifai N, Gillette MA, Carr SA (2006) Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 24:971–983PubMedCrossRef Rifai N, Gillette MA, Carr SA (2006) Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 24:971–983PubMedCrossRef
70.
go back to reference Kyselova Z, Mechref Y, Al Bataineh MM, Dobrolecki LE, Hickey RJ, Vinson J et al (2007) Alterations in the serum glycome due to metastatic prostate cancer. J Proteome Res 6:1822–1832PubMedCentralPubMedCrossRef Kyselova Z, Mechref Y, Al Bataineh MM, Dobrolecki LE, Hickey RJ, Vinson J et al (2007) Alterations in the serum glycome due to metastatic prostate cancer. J Proteome Res 6:1822–1832PubMedCentralPubMedCrossRef
71.
73.
go back to reference Petricoin EF 3rd, Espina V, Araujo RP, Midura B, Yeung C, Wan X et al (2007) Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival. Cancer Res 67:3431–3440PubMedCrossRef Petricoin EF 3rd, Espina V, Araujo RP, Midura B, Yeung C, Wan X et al (2007) Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival. Cancer Res 67:3431–3440PubMedCrossRef
74.
go back to reference Zhu H, Cox E, Qian J (2012) Functional protein microarray as molecular decathlete: a versatile player in clinical proteomics. Proteomics Clin Appl 6:548–562PubMedCentralPubMedCrossRef Zhu H, Cox E, Qian J (2012) Functional protein microarray as molecular decathlete: a versatile player in clinical proteomics. Proteomics Clin Appl 6:548–562PubMedCentralPubMedCrossRef
75.
go back to reference Rapkiewicz A, Espina V, Zujewski JA, Lebowitz PF, Filie A, Wulfkuhle J et al (2007) The needle in the haystack: application of breast fine-needle aspirate samples to quantitative protein microarray technology. Cancer 111:173–184PubMedCrossRef Rapkiewicz A, Espina V, Zujewski JA, Lebowitz PF, Filie A, Wulfkuhle J et al (2007) The needle in the haystack: application of breast fine-needle aspirate samples to quantitative protein microarray technology. Cancer 111:173–184PubMedCrossRef
76.
go back to reference Pierobon M, Calvert V, Belluco C, Garaci E, Deng J, Lise M et al (2009) Multiplexed cell signaling analysis of metastatic and nonmetastatic colorectal cancer reveals COX2-EGFR signaling activation as a potential prognostic pathway biomarker. Clin Colorectal Cancer 8:110–117CrossRef Pierobon M, Calvert V, Belluco C, Garaci E, Deng J, Lise M et al (2009) Multiplexed cell signaling analysis of metastatic and nonmetastatic colorectal cancer reveals COX2-EGFR signaling activation as a potential prognostic pathway biomarker. Clin Colorectal Cancer 8:110–117CrossRef
77.
go back to reference Liotta LA, Espina V, Mehta AI, Calvert V, Rosenblatt K, Geho D et al (2003) Protein microarrays: meeting analytical challenges for clinical applications. Cancer Cell 3:317–325PubMedCrossRef Liotta LA, Espina V, Mehta AI, Calvert V, Rosenblatt K, Geho D et al (2003) Protein microarrays: meeting analytical challenges for clinical applications. Cancer Cell 3:317–325PubMedCrossRef
78.
go back to reference Ellington AA, Kullo IJ, Bailey KR, Klee GG (2010) Antibody-based protein multiplex platforms: technical and operational challenges. Clin Chem 56:186–193PubMedCentralPubMedCrossRef Ellington AA, Kullo IJ, Bailey KR, Klee GG (2010) Antibody-based protein multiplex platforms: technical and operational challenges. Clin Chem 56:186–193PubMedCentralPubMedCrossRef
79.
go back to reference Weibrecht I, Leuchowius KJ, Clausson CM, Conze T, Jarvius M, Howell WM et al (2010) Proximity ligation assays: a recent addition to the proteomics toolbox. Expert Rev Proteomics 7:401–409PubMedCrossRef Weibrecht I, Leuchowius KJ, Clausson CM, Conze T, Jarvius M, Howell WM et al (2010) Proximity ligation assays: a recent addition to the proteomics toolbox. Expert Rev Proteomics 7:401–409PubMedCrossRef
80.
go back to reference Seidal T, Balaton AJ, Battifora H (2001) Interpretation and quantification of immunostains. Am J Surg Pathol 25:1204–1207PubMedCrossRef Seidal T, Balaton AJ, Battifora H (2001) Interpretation and quantification of immunostains. Am J Surg Pathol 25:1204–1207PubMedCrossRef
81.
go back to reference Haussmann U, Jahn O, Linning P, Janssen C, Liepold T, Portelius E et al (2013) Analysis of amino-terminal variants of amyloid-beta peptides by capillary isoelectric focusing immunoassay. Anal Chem 85:8142–8149PubMedCrossRef Haussmann U, Jahn O, Linning P, Janssen C, Liepold T, Portelius E et al (2013) Analysis of amino-terminal variants of amyloid-beta peptides by capillary isoelectric focusing immunoassay. Anal Chem 85:8142–8149PubMedCrossRef
82.
go back to reference Bentley C, Jurinka SS, Kljavin NM, Vartanian S, Ramani SR, Gonzalez LC et al (2013) A requirement for wild-type Ras isoforms in mutant KRas-driven signalling and transformation. Biochem J 452:313–320PubMedCrossRef Bentley C, Jurinka SS, Kljavin NM, Vartanian S, Ramani SR, Gonzalez LC et al (2013) A requirement for wild-type Ras isoforms in mutant KRas-driven signalling and transformation. Biochem J 452:313–320PubMedCrossRef
83.
go back to reference Wiegand KC, Hennessy BT, Leung S, Wang Y, Ju Z, McGahren M et al (2014) A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation. BMC Cancer 14:120PubMedCentralPubMedCrossRef Wiegand KC, Hennessy BT, Leung S, Wang Y, Ju Z, McGahren M et al (2014) A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation. BMC Cancer 14:120PubMedCentralPubMedCrossRef
85.
go back to reference Addona TA, Abbatiello SE, Schilling B, Skates SJ, Mani DR, Bunk DM et al (2009) Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nat Biotechnol 27:633–641PubMedCentralPubMedCrossRef Addona TA, Abbatiello SE, Schilling B, Skates SJ, Mani DR, Bunk DM et al (2009) Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nat Biotechnol 27:633–641PubMedCentralPubMedCrossRef
Metadata
Title
Capillary nano-immunoassays: advancing quantitative proteomics analysis, biomarker assessment, and molecular diagnostics
Authors
Jin-Qiu Chen
Lalage M Wakefield
David J Goldstein
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0537-6

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