IMPROVED CANCER BIOMARKER DETECTION USING NOVEL AIR AMPLIFIER DESIGNS IN ESI-MS


Year of Award:
2008
Award Type:
R21
Project Number:
CA134250
RFA Number:
RFA-CA-07-033
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
MUDDIMAN, DAVID C.
Other PI or Project Leader:
DOW, THOMAS A;EDWARDS, JACK RAY
Institution:
NORTH CAROLINA STATE UNIVERSITY RALEIGH
The identification and quantification of candidate biomarkers specific for a given cancer (e.g., ovarian, prostate) using tools such as liquid chromatography-mass spectrometry (LC-MS) is necessary for the diagnosis and treatment of the disease. Improved limits of detection for LC-MS and LC-tandem MS (LC-MS/MS) by implementation of devices such as the air amplifier proposed here will further these efforts enabling better patient care. Design using computer modeling and simulation, and fabrication using precision engineering methodologies will result in a stable, low tolerance air amplifier. The improved limits of detection by a well-designed and implemented air amplifier device will result in detection and quantification of low abundance candidate biomarkers in biofluids for both discovery-based and targeted proteomic applications. Systematic evaluation of the new air amplifier designs will utilize electrospray ionization mass spectrometry (ESI-MS). This will compare the original air amplifier design to the newly designed air amplifier based on the metrics of ionization time (MS analysis), limits of detection, and number of protein identifications from LC-MS/MS. After establishing a reproducible protocol for the air amplifier, it will be directly applicable for biomarker discovery and target based analysis. Multi-site evaluation of the improved air amplifier is proposed to determine inter-laboratory reproducibility. As a final element of this proposed research, the air amplifier design and application instructions will be disseminated on the internet for open access.