Dong, H., Mora, Jr., Brockus, C., Chilewski, Sd., Dodge, R., Merrifield, C., Dickerson, Wm., Desilva, B., Development Of A Generic Anti-Peg Antibody Assay Using Bioscale’s Acoustic Membrane Microparticle Technology, Aaps J. Epub 2015 Jul 3.
This paper describes the development of an anti-PEG antibody assay with Bristol Myers Squibb using AMMP Technology. The data indicate that an assay with a sensitivity of less than 1000 ng/mL for IgG is achievable. This level of sensitivity is better than current published reports on IgG anti-PEG antibody detection.
Chilewski, SD., Dickerson, WM., Mora, JR., Saab, A., Alderman, EM., Evaluation of Acoustic Membrane MicroParticle (AMMP) Technology for a Sensitive Ligand Binding Assay to Support Pharmacokinetic Determinations of a Biotherapeutic, AAPS J. 2014 Nov;16(6):1366-71. Epub 2014 Sep 23.
This paper describes work with Bristol Myers Squibb that involved the development of a PEGylated domain antibody biotherapeutic. The AMMP assay delivered sensitivity of 750pg/mL, far greater sensitivity than the majority of PK assays. Sensitivity, reproducibility, and selectivity met industry standards for PK analysis.
Cho Hh., Alderman, E., Kreder, N., Caro, Rg., Leong, K., Miller, Mf., Hill, Wa., Pandey, P., Competitive, immunometric assay for fusion protein quantification: protein production prioritization, Anal Biochem. 2014 Feb 1;446:1-8. Epub 2013 Oct 10.
The paper describes work with Novartis on a novel method to rank hexahistidine-tagged fusion proteins based on surface exposure and accessibility of the hexahistidine-tag. These technique greatly improves on the practice of SDS-PAGE denaturing gels or affinity columns since both classical methods have either proven to be only marginally predictive of the purification yield and authentic folding for native proteins, or are quantitative enough to low for the ranking of candidate constructs.
Z.-H. Yan Et Al., Analysis Of Two Pharmacodynamic Biomarkers Using Acoustic Micro Agnetic Particles On The Vibe Bioanalyzer, Anal Biochem. 2011 Mar 1;410(1):13-8. Epub 2010 Nov 13.
This publication describes the development of acoustic assays for two pharmacodynamic pathway biomarkers, Akt1 and GADD34, and a comparison by Takeda/Millennium to AlphaScreen and LI-COR Western blot assays. The results in the authors’ own words show clearly that the acoustic assay technology “is a robust and rapid method for measuring recombinant standards or endogenously derived proteins from both tissue culture and mouse xenograft tumor lysates. Moreover, the sensitivity obtained with the BioScale platform compares favorably with LI-COR Western blot and AlphaScreen technologies. Furthermore, the use of the ViBE Bioanalyzer eliminates the labor-intensive effort of Western blot analysis and is devoid of the optical and other endogenous interfering substances derived from lysates of xenograft tumors typically observed with AlphaScreen.”
Yuan TL, Fellmann C, Lee CS, Ritchie CD, Thapar V, Lee LC, Hsu DJ, Grace D, Carver JO, Zuber J, Luo J, McCormick F, Lowe SW. Development of siRNA payloads to target KRAS-mutant cancer. Cancer Discov. 2014 Oct;4(10):1182-97. dos 10.1158/2159-8290.CD-13-0900. Epub 2014 Aug 6.
This study describes development by University of California at San Francisco of a targeted siRNA-mediated ablation screen to identify key regulatory nodes in KRAS-mutant cell lines. The ViBE technology was used to map the phosphorylation status of key kinase targets, an approach that was more quantitative and less labor intensive than Western blotting.
Jalali-Yazdi, F., Corbin, JM., Takahashi, TT., Roberts, RW., Robust, Quantitative Analysis of Proteins using Peptide Immunoreagents, in Vitro Translation, and an Ultrasensitive Acoustic Resonant Sensor, Anal Chem. 2014 May 20;86(10):4715-22. Epub 2014 May 2.
The study describes development by University of Southern California of a quantitative method to analyze protein-protein interactions and rank-order their relative binding affinities for the cancer marker Bcl-xL. The developed method has 4- to 10-fold higher sensitivity, uses 100-fold less protein and 5-fold less antibody per sample, when compared directly with ELISA. A major benefit is also that this analysis was conducted in complex mixtures at physiological ionic strength.
Negroni L, Taouji S, Arma D, Pallares-Lupon N, Leong K, Beausang LA, Latterich M, Bossé R, Balabaud C, Schmitter JM, Bioulac-Sage P, Zucman-Rossi J, Rosenbaum J, Chevet E. Integrative quantitative proteomics unveils proteostasis imbalance in human hepatocellular carcinoma developed on nonfibrotic livers. Mol Cell Proteomics. 2014 Dec;13(12):3473-83. doi: 10.1074/mcp.M114.043174. Epub 2014 Sep 15.
This paper describes the proteomic identification of differentially expressed and phosphorylated peptides between non-fibrotic liver and hapatocellular carcinoma developed on non-fibrotic liver. The ViBE platform was used to validate the significance of one of the identified phosphorylation sites on calnexin in a cohort of clinical specimens.
Fraser, S., Cameron, M., O’Connor, E., Schwickart, M., Tanen, M., Ware, M., Next generation ligand binding assays-review of emerging real-time measurement technologies, AAPS J. 2014 Sep;16(5):914-24. Epub 2014 Jul 25.
This paper is a description of six emerging real-time measurement technologies for ligand binding assays, including AMMP Technology. The various development stages of each technology is explored, from pre-commercial to commercially available. Demonstrated applications for each technology and a comprehensive summary of the technology attributes is also discussed.
Collins, CM., Yui, S., Roberts, CE., Kojic, I., Thrombin detection using a piezoelectric aptamer-linked immunosorbent assay, Anal Biochem. 2013 Dec1;443(1):97-103. Epub 2013 Aug 28.
The study describes the development of a sensitive and reproducible acoustic assay that uses DNA aptamers as capture and detection agents. The method provides a robust and rapid detection of thrombin in human serum while also eliminating the labor-intensive efforts of Western blot analysis and is not affected by the interfering substances found in serum that often affect optical-based and antibody-based detection systems.
Dickerson, Wm., Saab, A., Leong, K., Miller, M., Latterich, M., Beausang La., Alderman, Em., Measurement of downstream kinase activity modulation as indicator of epidermal growth factor receptor inhibitor efficacy, Anal Biochem. 2014 March 1;448:65-7. Epub 2013 Dec 6.
The study describes the use of acoustic assays to reveal network relationships of kinase pathways related to cancer signaling pathways. This study substantiates that EGFR stimulation predominantly activates the MEK/ERK pathway. The EGFR inhibitors tested had varying effectiveness at preventing phosphorylation at the EGFR or downstream kinase activity. These experiments highlight the use of acoustic assays for observing multiple signaling pathways in a single experiment.