? We propose to develop a novel micromachined ultrasonic electrospray source which eliminates most, if not all, limitations of the conventional ESI technology, thereby providing scientists involved in biomedicine, functional proteomics and biomarker discovery with a unique MS interface for high throughput, ultrasensitive, and multiplexed analysis of proteins mixtures of biological significance. The proposed technology called AMUSE (Array of Micromachined UltraSonic Electrospray) ion source has potential for operation at low voltages with wide range of solvents, capable of minimizing the required sample size and improving sample utilization, and is inherently suitable for parallel, high throughput operation with multiplexing in the array format. Further, the ultrasonic electrospray source can be made inexpensive to be disposable since it is batch microfabricated using a simple process. We will design and fabricate the prototype(s) of the micromachined ultrasonic electrospray source array for use in mass spectrometric analysis of protein mixtures of biological relevance. We will test and optimize the performance of both ESI device concepts and to clearly quantify their potential advantages. We will evaluate the analytical performance of a time-of-flight mass spectrometer outfitted with the proposed micromachined ultrasonic electrospray source and compare it with existing commercial nanospray ion sources. Development of an improved electrospray source for protein mass spectrometry, as proposed here, would enable identification of new biomarkers of various human deceases, including various types of cancers. In addition, mass spectrometry is routinely used in drug development, and therefore the advancement of electrospray mass spectrometry will contribute directly to improvement in public health. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21RR021474-01A1
Application #
7088593
Study Section
Special Emphasis Panel (ZRR1-BT-6 (01))
Program Officer
Friedman, Fred K
Project Start
2006-09-15
Project End
2009-06-30
Budget Start
2006-09-15
Budget End
2007-06-30
Support Year
1
Fiscal Year
2006
Total Cost
$178,002
Indirect Cost
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
Forbes, Thomas P; Degertekin, F Levent; Fedorov, Andrei G (2011) Droplet charging regimes for ultrasonic atomization of a liquid electrolyte in an external electric field. Phys Fluids (1994) 23:12104
Forbes, Thomas P; Degertekin, F Levent; Fedorov, Andrei G (2010) Electrohydrodynamics of charge separation in droplet-based ion sources with time-varying electrical and mechanical actuation. J Am Soc Mass Spectrom 21:501-10
Forbes, Thomas P; Degertekin, F Levent; Fedorov, Andrei G (2010) Electrochemical Ionization and Analyte Charging in the Array of Micromachined UltraSonic Electrospray (AMUSE) Ion Source. J Electroanal Chem (Lausanne) 645:167-173
Forbes, Thomas P; Degertekin, F Levent; Fedorov, Andrei G (2010) Regime transition in electromechanical fluid atomization and implications to analyte ionization for mass spectrometric analysis. J Am Soc Mass Spectrom 21:1900-5
Forbes, Thomas P; Dixon, R Brent; Muddiman, David C et al. (2009) Characterization of charge separation in the Array of Micromachined UltraSonic Electrospray (AMUSE) ion source for mass spectrometry. J Am Soc Mass Spectrom 20:1684-7
Hampton, Christina Y; Silvestri, Catherine J; Forbes, Thomas P et al. (2008) Comparison of the internal energy deposition of Venturi-assisted electrospray ionization and a Venturi-assisted array of micromachined ultrasonic electrosprays (AMUSE). J Am Soc Mass Spectrom 19:1320-9
Hampton, Christina Y; Forbes, Thomas P; Varady, Mark J et al. (2007) Analytical performance of a venturi-assisted array of micromachined ultrasonic electrosprays coupled to ion trap mass spectrometry for the analysis of peptides and proteins. Anal Chem 79:8154-61
Forbes, Thomas P; Degertekin, F Levent; Fedorov, Andrei G (2007) Multiplexed operation of a micromachined ultrasonic droplet ejector array. Rev Sci Instrum 78:104101
Dixon, R Brent; Muddiman, David C; Hawkridge, Adam M et al. (2007) Probing the mechanisms of an air amplifier using a LTQ-FT-ICR-MS and fluorescence spectroscopy. J Am Soc Mass Spectrom 18:1909-13