Mass spectrometry (MS)-based proteomics and metabolomics enable broad, in-depth profiling of biomolecules and their abundances, and are critical for understanding cellular structure and function. However, due to sensitivity and throughput limitations, samples comprising a minimum of several thousand cells are generally required for global ‘omics’ measurements, and each analysis can require hours to complete. Recent advances in enabling technologies such as single-cell imaging offer some promise towards biomolecular characterization of tissue microenvironments, but these technologies share a common shortcoming in that only a limited number of molecular species can be analyzed. New technology is crucially needed that combines depth of coverage and ultra-high throughput.
My laboratory will focus on extending in-depth biological MS analyses to single cells and beyond. By dramatically increasing measurement sensitivity and throughput, we will be able to generate biomolecular maps comprising thousands of molecules within biological tissues at single cell resolution. This will provide understand of the influence of tissue organization and microenvironments on the molecular state of cells within those tissues, providing a wealth of information regarding developmental biology, disease development and heterogeneous responses to treatment among different cell types and microenvironments.
Achieving these long-term goals requires advances in sample preparation, separation, ionization and mass analysis. As such, our research efforts will span multiple technologies including robotics and microfluidics for nanoscale sample preparation, improved liquid-phase separations (e.g., liquid chromatography and capillary electrophoresis), increasing the efficiency of nanoelectrospray ionization, and enhancing ion transmission and mass analysis. We will apply these nanoscale omic measurements to a variety of biological systems, working in close collaboration with biologists and clinicians.
Publications
2018
Dou, M.; Chouinard, C. D.; Zhu, Y.; Nagy, G.; Liyu, A. V.; Ibrahim, Y. M.; Smith, R. D.; Kelly, R. T. Nanowell-Mediated Multidimensional Separations Combining nanoLC with SLIM IM-MS for Rapid, High-Peak-Capacity Proteomic Analyses,Bioanal. Chem.,2018, DOI: 10.1007/s00216-018-1452-5.
Hutchinson, J. R.; Erikson, R. L.; Sheen, A. M.; Ozanich, R. M.; Kelly, R. T.* Rapid, Sensitive and Field-Portable Detection of Bacillus anthracisSpores Using Simple Microfluidic Device and Smartphone-Based Microscopy, Analyst,2015, 140, 6269–6276.
Kelly, R. T.*; Wang, C.; Rausch, S. J.; Lee, C. S.; Tang, K. Pneumatic Microvalve-Based Hydrodynamic Sample Injection for High Throughput, Quantitative Zone Electrophoresis in Capillaries, Anal. Chem. 2014, 6723–6729,dx.doi.org/10.1021/ac501910p.
Cox, J. T.; Marginean, I.; Kelly, R. T.; Smith, R. D.; Tang, K. Improving the Sensitivity of Mass Spectrometry by Using a New Sheath Flow Electrospray Emitter Array at Subambient Pressures, J. Am. Soc. Mass Spectrom.,2014,25, 2028–2037.
Vasdekis, A. E.; Wilkins, M. J.; Grate, J. W.; Kelly, R. T.; Konopka, A. E.; Xantheas, S. S.; Chang, T.-M. Solvent Immersion Imprint Lithography, Lab Chip,2014,14, 2072–2080.
Marginean, I.; Tang, K.; Smith, R. D.; Kelly, R. T.* Picoelectrospray Ionization Mass Spectrometry using Narrow-Bore Chemically Etched Emitters , J. Am. Soc. Mass Spectrom.,2014,25, 30–36.
Jambovane, S.; Prost, S. A.; Sheen, A. S.; Magnuson, J. K.; Kelly, R. T. On-Demand Serial Dilution using Quantized Nano/Picoliter-Scale Droplets. In Micro Total Analysis Systems 2014, Jacobson, S. C.; Kutter, J. P., Eds. Chemical and Biochemical Microsystems Society: San Diego, CA, 2014; pp. 1247–1249 (conference proceedings).
Cong, Y.; Rausch, S. J.; Geng, T.; Jambovane, S.; Kelly, R. T. Pneumatic Microvalve for Electrokinetic Sample Preconcentration and Capillary Electrophoresis Injection. In Micro Total Analysis Systems 2014, Jacobson, S. C.; Kutter, J. P., Eds. Chemical and Biochemical Microsystems Society: San Diego, CA, 2014; pp. 2560–2561 (conference proceedings).
Sun, X.; Kelly, R. T. Biological Sample Preparation and Analysis using Droplet-Based Microfluidics. In Nanopatterning and Nanoscale Devices for Biological Applications Selimovic, S, Ed. CRC Press: Boca Raton, FL 2014; 73–92 (book chapter).
Kelly, R. T.; Marginean, I.; Tang, K. Electrospray Ionization Mass Spectrometry. In Encyclopedia of Microfluidics and Nanofluidics Li, D. ed. SpringerReference, 2014; Article ID: 66694, DOI: 10.1007/978-3-642-27758-0_460-5 (book chapter).
Sun, X.; Kelly, R. T. Droplet-Based Microfluidics for Biological Sample Preparation and Analysis. In Technologies for Smart Sensors and Sensor Fusion. Yallup, K. and Iniewski, K. eds. CRC Press: Boca Raton, FL 2014; 3–18 (book chapter).
Sun, X.; Kelly, R. T Droplet-Based Microfluidics for Biological Sample Preparation and Analysis. In Microfluidics and Nanotechnology: Biosensing to the Single Molecule Limit Lagally, E. T., ed. CRC Press: Boca Raton, FL, 2014, 201–220 (book chapter).
2013
Kelly, R. T.*; Sheen, A. M.; Jambovane, S. Multilayer microfluidic devices created from a single photomask, RSC Advances,2013, 3, 20138–20142.
Sun, X.; Tang, K.; Smith, R. D.; Kelly, R. T.* Controlled dispensing and mixing of pico- to nanoliter volumes using on-demand droplet-based microfluidics Microfluid. Nanofluid.,2013,15, 117–126.
Grate, J. W.; Zhang, C. Y.; Wilkins, M.; Warner, M. G.; Anheier, N. C.; Suter, J.; Kelly, R.; Oostrom, M. Chemical Sensing and Imaging in Microfluidic Pore Network Structures Relevant to Natural Carbon Cycling and Industrial Carbon Sequestration. Proc. SPIE,2013,8725, 872522 (conference proceedings).
2012
Grate, J. W.; Kelly, R. T.; Suter, J.; Anheier, N. C. Silicon-on-Glass Pore Network Micromodels with Oxygen Sensing Fluorophore Films for Chemical Imaging and Defined Spatial Structure Lab Chip,2012,12, 4796–4801.
Angel, T. E.; Aryal, U. K.; Hengel, S. M.; Baker, E. S.; Kelly, R. T.; Robinson, E. W.; Smith, R. D. Mass Spectrometry Based Proteomics: Existing Capabilities and Future Directions Chem. Soc. Rev.2012,41, 3912–3928 (review).
Sun, X.; Tang, K.; Smith, R. D.; Kelly, R. T. Robust Extraction Interface for Coupling Droplet-Based and Continuous Flow Microfluidics. In Advances in Microfluidics Kelly, R. T. ed. Intech: New York, 2012; 155-170 (book chapter).
2011
Tang, K.; Page, J. S.; Marginean, I.; Kelly, R. T.; Smith, R. D. Improving Liquid Chromatography-Mass Spectrometry Sensitivity Using Subambient Pressure Ionization with Nanoelectrospray (SPIN) Interface J. Am. Soc. Mass Spectrom.2011,22, 1318–1325.
Sun, X.; Kelly, R. T.*; Tang, K., Smith, R. D. Membrane-Based Emitter for Coupling Microfluidics with Ultrasensitive Nanoelectrospray Ionization-Mass Spectrometry Anal. Chem.2011,83, 5797–5803 (technical note).
Sun, X.; Kelly, R. T.*; Danielson, W. F.; Agrawal, N.; Tang, K.; Smith, R. D. Hydrodynamic Injection with Pneumatic Valving for Microchip Electrophoresis with Total Analyte Utilization Electrophoresis,2011,32, 1610–1618.
Hossain, M.; Kaleta, D. T.; Robinson, E. W.; Liu, T.; Zhao, R.; Page, J. S.; Kelly, R. T.; Moore, R. J.; Tang, K.; Camp, D. G.; Qian, W.-J.; Smith, R. D. Enhanced Sensitivity for Selected Reaction Monitoring Mass Spectrometry-based Targeted Proteomics using a Dual-Stage Electrodynamic Ion Funnel Interface Mol. Cell. Proteomics. 2011, 2011 10: M000062-MCP201 (cover article).
2010
Sun, X.; Kelly, R. T.; Tang, K.; Smith, R. D. Ultrasensitive Nanoelectrospray Ionization-Mass Spectrometry using Poly(dimethylsiloxane) Microchips with Monolithically Integrated Emitters Analyst,2010,135, 2296-2302.
Kelly, R. T.; Tolmachev, A. V.; Page, J. S.; Tang, K.; Smith, R. D. The Ion Funnel: Theory, Implementations and Applications Mass Spectrom. Rev.2010, 29, 294-312 (review).
Tang, K.; Page, J. S.; Kelly, R. T.; Marginean, I. Electrospray Ionization in Mass Spectrometry. In Encyclopedia of Spectroscopy and Spectrometry, 2nd Edition. Lindon, J. C.; Tranter, G. E.; Koppenaal D. W., Eds. Academic Press: Oxford, UK, 2010; pp. 467–474 (book chapter).
2009
Page, J. S.; Marginean, I.; Baker, E. S.; Kelly, R. T.; Tang, K.; Smith, R. D. Biases in Ion Transmission through an ESI-MS Capillary Inlet J. Am. Soc. Mass Spectrom.2009,20, 2265–2272.
Marginean, I.; Page, J. S.; Kelly, R. T.; Tang, K.; Smith, R. D. Effect of Pressure on Electrospray Characteristics Appl. Phys. Lett.2009,95, 184103 (communication).
Mabrouki, R.; Kelly, R. T.; Prior, D. C.; Shvartsburg, A. A.; Tang, K.; Smith, R. D. Improving FAIMS Sensitivity using a Planar Geometry with Slit Interfaces J. Am. Soc. Mass Spectrom.2009,20, 1768–1774.
Kelly, R. T.*; Page, J. S.; Marginean, I.; Tang, K.; Smith, R. D. Dilution-Free Analysis from Picoliter Droplets by Nano-Electrospray Ionization Mass Spectrometry Angew. Chem.2009,121, 6964–6967; Angew. Chem. Int. Ed.2009,48, 6832–6835 (communication).
Marginean, I.; Kelly, R. T.; Moore, R. J.; Prior, D. C.; LaMarche, B. L.; Tang, K.; Smith, R. D. Selecting the optimum electrospray voltage for gradient elution LC-MS measurements J. Am. Soc. Mass Spectrom.2009,20, 682–688.
2008
Marginean, I.; Kelly, R. T.; Prior, D. C.; LaMarche, B.; Tang, K.; Smith, R. D. Analytical Characterization of the Electrospray Ion Source in the Nanoflow Regime Anal. Chem.2008,80, 6573–6579.
Kelly, R. T.; Page, J. S.; Marginean, I.; Tang, K.; Smith, R. D. Nanoelectrospray Emitter Arrays Providing Inter-Emitter Electric Field Uniformity Anal. Chem. 2008,80, 5660–5665.
Kelly, R. T.; Tang, K.; Irimia, D.; Toner, M.; Smith, R.D. Elastomeric Microchip Electrospray Emitter for Stable Cone-Jet Mode Operation in the Nano-Flow Regime Anal. Chem.2008,80, 3824–3831.
Page, J. S.; Tang, K.; Kelly, R. T.; Smith, R. D. Subambient Pressure Ionization with Nanoelectrospray Source and Interface for Improved Sensitivity in Mass Spectrometry Anal. Chem.2008,80, 1800–1805.
Livesay, E. A.; Tang, K.; Taylor, B. K.; Buschbach, M. A.; Hopkins, D. F.; LaMarche, B. L.; Zhao, R.; Shen, Y.; Orton, D. J.; Moore, R. J.; Kelly, R. T.; Udseth, H. R.; Smith, R. D. Fully Automated Four-Column Capillary LC–MS System for Maximizing Throughput in Proteomic Analyses Anal. Chem.2008,80, 294–302.
Kelly, R. T.; Page, J. S. Zhao, R.; Qian, W.-J.; Mottaz, H. M.; Tang, K.; Smith, R. D. Capillary-Based Multi-Nanoelectrospray Emitters: Improvements in Ion Transmission Efficiency and Implementation with Capillary Reversed-Phase LC-ESI-MS Anal. Chem.2008,80, 143–149.
Page, J. S.; Kelly, R. T.; Camp, D. G.; Smith, R. D. Improving low-level plasma protein mass spectrometry-based detection for candidate biomarker discovery and validation ICBC Newsletter2008,3(3) (newsletter feature article).
2007
Yang, F.; Camp II, D. G.; Gritsenko, M. A.; Luo, Q.; Kelly, R. T.; Clauss, T. R. W.; Brinkley, W. R.; Smith, R. D.; Stenoien, D. L. Identification of a Novel Mitotic Phosphorylation Motif Associated with Protein Localization in the Mitotic Apparatus J. Cell Sci.2007,120, 4060–4070.
Marginean, I.; Kelly, R. T.; Page, J. S.; Tang, K.; Smith, R. D. Electrospray Characteristic Curves: In Pursuit of Improved Performance in the Nano-Flow Regime Anal. Chem.2007,79, 8030–8036.
Page, J. S.; Kelly, R. T.; Tang, K.; Smith, R. D. Ionization and Transmission Efficiency in an Electrospray Ionization-Mass Spectrometry Interface J. Am. Soc. Mass Spectrom.2007,18, 1582–1590.
Kelly, R. T.; Page, J. S.; Tang, K; Smith, R. D. Array of Chemically Etched Fused Silica Emitters for Improving the Sensitivity and Quantitation of Electrospray Ionization Mass Spectrometry. Anal. Chem.2007,79, 4192–4198.
Kelly, R. T.; Woolley, A. T. Microchip Capillary Electrophoresis Systems for DNA Analysis. In Bio-MEMS Technology and Applications Wang, W.; Soper, S. A., Eds. CRC Press: Boca Raton, FL, 2007; pp. 349–362 (book chapter).
2006
Kelly, R. T.; Page, J. S.; Luo, Q.; Moore, R. J.; Orton, D. J.; Tang, K.; Smith, R. D. Chemically Etched Open Tubular and Monolithic Emitters for Nano-electrospray Ionization Mass Spectrometry. Anal. Chem.2006,78, 7796–7801.
Kelly, R. T.; Li, Y.; Woolley, A. T. Phase-Changing Sacrificial Materials for Interfacing Microfluidics with Ion-Permeable Membranes to Create On-Chip Preconcentrators and Electric Field Gradient Focusing Microchips. Anal. Chem.2006,78, 2565–2570.
2005
Kelly, R. T.; Pan, T.; Woolley, A. T. Phase-Changing Sacrificial Materials for Solvent Bonding of High-Performance Polymeric Capillary Electrophoresis Microchips. Anal. Chem.,2005,77, 3536–3541.
Peeni, B. A.; Conkey, D. B.; Barber, J. P.; Kelly, R. T.; Lee, M. L.; Woolley, A. T.; Hawkins, A. R. Planar Thin Film Device for Capillary Electrophoresis. Lab Chip,2005,5, 501–505.
Kelly, R. T.; Woolley, A. T. Microfluidic Systems for Integrated, High-Throughput DNA Analysis. Anal. Chem.,2005,77, 96A–102A (feature, cover article).
Warnick, K. F.; Francom, S. J.; Humble, P. H.; Kelly, R. T.; Woolley, A. T.; Lee, M. L.; Tolley, H. D. Field Gradient Electrophoresis. Electrophoresis2005,26, 405–414.
Kelly, R. T.; Woolley, A. T. Electric Field Gradient Focusing. J. Sep. Sci.2005,28, 1985–1993 (review).
Kelly, R. T.; Humble, P. H., Lee, M. L.; Woolley, A. T. Phase-Changing Sacrificial Materials for the Fabrication of Microfluidic Analysis Systems in Polymers. In Micro Total Analysis Systems 2005, Jensen, K. V.; Han, J.; Harrison, D. J.; Voldman, J., Eds. Transducer Research Foundation: San Diego, CA, 2005; pp 196–198 (conference proceedings).
2004
Humble, P. H.; Kelly, R. T.; Woolley, A. T.; Tolley, H. D.; Lee, M. L. Electric Field Gradient Focusing of Proteins Based on Shaped Ionically Conductive Acrylic Polymer. Anal. Chem.2004,76, 5641–5648.
Pan, T.; Kelly, R. T.; Asplund, M. C.; Woolley, A. T. Fabrication of Calcium Fluoride Capillary Electrophoresis Microdevices for On-Chip Infrared Detection. J. Chromatogr., A 2004,1027, 231–235.
2003
Kelly, R. T.; Woolley, A. T. Thermal Bonding of Polymeric Capillary Electrophoresis Microdevices in Water. Anal. Chem.2003,75, 1941–1945 (technical note).
2001
Woolley, A. T.; Kelly, R. T. Deposition and Characterization of Extended Single-Stranded DNA Molecules on Surfaces. Nano Lett.2001,1, 345–348 (communication).