ELECTROSPRAY TANDEM TIME-OF-FLIGHT MASS SPECTROMETER

THE OVERALL OBJECTIVE OF THIS RESEARCH IS TO CONTINUE TO IMPROVE ELECTROSPRAY IONIZATION MASS SPECTROMETRY (ESPI-MS) FOR THE ANALYSIS OF BIOLOGICAL MACROMOLECULES. AS A METHOD CAPABLE OF DELIVERING EXTREMELY LARGE MOLECULES INTO THE GAS PHASE AS INTACT DESOLVATED MOLECULAR IONIC SPECIES FROM THEIR POLAR SOLVENTS, ESPI-MS HAS BEEN EFFECTIVELY EXPLOITEDIN DETERMINING THE MOLECULAR WEIGHTS OF PEPTIDES, SMALL PROTEINS, AND NUCLEIC ACID CONSTITUENTS. THE SPECIFIC AIM OF THE RESEARCH IS TO DEMONSTRATE THE FEASIBILITY OF AN ESPI TANDEM TIME-OF-FLIGHT (TOF) MS WITH UNLIMITED MASS RANGE, HIGH SENSITIVITY, LOW COST, SIMPLE OPERATION, AND SUFFICIENT MASS RESOLUTION TO OPERATE AT LARGE (CA. 5,000) M/Z VALUES. OPTIMIZATION OF BOTH RESOLUTION AND FRAGMENTATION CONTROL WILL BE STRESSED. THE LONG-TERM OBJECTIVE IS TO DEVELOP EXPERIMENTAL STRATEGIES FOR THE CONTROLLED FRAGMENTATION OF BIOMOLECULES USING A MS/MS INSTRUMENT BASED ENTIRELY ON TOF TECHNOLOGY, YIELDING BOTH MOLECULAR WEIGHT AND STRUCTURAL INFORMATION. THIS EFFORT WILL BE DRIVEN BY BOTH PHASE I PROTOTYPE RESULTSAS WELL AS RECENT IMPROVEMENTS IN HIGH-RESOLUTION TOF DEVICES. IT IS EXPECTED THAT THIS TECHNIQUE WILL IMPROVE MASS SPECTROMETRIC CAPABILITIES IN IDENTIFYING VERY LIMITED QUANTITIES OF A SAMPLE AT A RELATIVELY LOW COST. FURTHERMORE, BY REDUCING THE SPECTROMETER OPERATIONAL COMPLEXITY WITH THE EMPLOYMENT OF TOF, IT IS PROBABLE THAT THIS MS/MS INSTRUMENT WILL BE ACCESSIBLE TO NONMASS SPECTROSCOPISTS AS WELL.