Abstract

The primary goal of the project is to develop mass spectrometry (MS) based assays for high throughput and quantitative biomarker validation with sensitivity and specificity comparable to or better than antibody based immunoassays. The analytical platform will be primarily based on triple quadrupole mass spectrometry with its sensitivity, dynamic range, measurement specificity and sample throughput significantly enhanced by integrating the latest high speed liquid chromatography (LC), high efficiency electrospray ionization (ESI) source and unique MS interface technologies developed at Pacific Northwest National Laboratory (PNNL) and extending the instrument capability from performing traditional multiple reaction monitoring (MRM) measurements into MRM2 MS analysis. The expected limit of quantitation and dynamic range for the new instrument based assays will be expected to reach low pg/mL level and span eight orders of magnitude in sample concentration allowing quantitative measurements of low abundance protein biomarkers in complex biofluids, such as human blood plasma. The new instrument based assays will be applicable to a broad spectrum of clinical cancer biomarker validation applications and capable of validating hundreds to thousands biomarkers in a single experiment. Their performance will be rigorously optimized and tested using clinical samples.

Public Health Relevance

The development of mass spectrometry (MS) based assays for high throughput and quantitative biomarker validation with sensitivity and specificity comparable to or better than antibody based immunoassays.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA155252-03
Application #
8511583
Study Section
Special Emphasis Panel (ZCA1-SRLB-R (O1))
Program Officer
Kagan, Jacob
Project Start
2011-08-18
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$408,071
Indirect Cost
$206,904

  Institution

Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352

  Publications

Guo, Xuejiang; Fillmore, Thomas L; Gao, Yuqian et al. (2016) Capillary Electrophoresis-Nanoelectrospray Ionization-Selected Reaction Monitoring Mass Spectrometry via a True Sheathless Metal-Coated Emitter Interface for Robust and High-Sensitivity Sample Quantification. Anal Chem 88:4418-25
Liu, Tianbiao; Cox, Jonathan T; Hu, Dehong et al. (2015) A fundamental study on the [(?-Cl)3Mg2(THF)6]+ dimer electrolytes for rechargeable Mg batteries. Chem Commun (Camb) 51:2312-5
Cox, Jonathan T; Marginean, Ioan; Smith, Richard D et al. (2015) On the ionization and ion transmission efficiencies of different ESI-MS interfaces. J Am Soc Mass Spectrom 26:55-62
Chen, Tsung-Chi; Fillmore, Thomas L; Prost, Spencer A et al. (2015) Orthogonal Injection Ion Funnel Interface Providing Enhanced Performance for Selected Reaction Monitoring-Triple Quadrupole Mass Spectrometry. Anal Chem 87:7326-31
Cox, Jonathan T; Marginean, Ioan; Kelly, Ryan T et al. (2014) Improving the sensitivity of mass spectrometry by using a new sheath flow electrospray emitter array at subambient pressures. J Am Soc Mass Spectrom 25:2028-37
Marginean, Ioan; Tang, Keqi; Smith, Richard D et al. (2014) Picoelectrospray ionization mass spectrometry using narrow-bore chemically etched emitters. J Am Soc Mass Spectrom 25:30-6
Cox, Jonathan T; Kronewitter, Scott R; Shukla, Anil K et al. (2014) High sensitivity combined with extended structural coverage of labile compounds via nanoelectrospray ionization at subambient pressures. Anal Chem 86:9504-11
Kelly, Ryan T; Wang, Chenchen; Rausch, Sarah J et al. (2014) Pneumatic microvalve-based hydrodynamic sample injection for high-throughput, quantitative zone electrophoresis in capillaries. Anal Chem 86:6723-9
Shi, Tujin; Sun, Xuefei; Gao, Yuqian et al. (2013) Targeted quantification of low ng/mL level proteins in human serum without immunoaffinity depletion. J Proteome Res 12:3353-61
Wang, Chenchen; Lee, Cheng S; Smith, Richard D et al. (2013) Capillary isotachophoresis-nanoelectrospray ionization-selected reaction monitoring MS via a novel sheathless interface for high sensitivity sample quantification. Anal Chem 85:7308-15

Showing the most recent 10 out of 14 publications