Nano/Micro Mass Spectrometry


Our lab is investigating new sampling and emitting techniques for electrospray ionization mass spectrometry (ESI-MS), matrix-assisted laser desorption/ionization (MALDI), and other MS methods. Through use of nanopipettes, or capillaries pulled to less than 100 nm in size, as sample emitters, higher signal-to-noise ratios are observed in MS analyses when compared to commercial ESI-MS emitters. Moreover, the size scale of nanopipettes is amenable to biological sampling. Together, these contributions sum to give improved mass spectra from biologically relevant systems. Active projects include development of a new scanning probe microscopy technique based on electrospray, termed scanning electrospray microscopy (SESM), as well as development of a mobile theta pipette-based microfluidic segmented flow sampling device.

Push-pull microfluidic sampling device

A mobile push-pull microfluidic device was developed to enable collection of multiple layers of sample (picoliter volume) while maintaining spatial registry. Subsequently, the theta pipettes were used as electrospray emitters for dilution-free analysis of individual sample plugs without multiple sample transfer steps. The miniaturized probe inlet enables sample collection with high spatial resolution and temporal resolution of sample collection can be as high as 0.7 Hz. This device can find application in study of sample heterogeneity and local chemical changes in biological samples.

Push-pull sampling

Figure 1. (a) Optical micrograph of a pipette with aqueous and perfluorodecalin segments. A solution of disodiumfluoroscein was used to make the aqueous segments appear green due to the fluorescence of disodiumfluoroscein. (b) A schematic depicting segmented flow sampling where the theta pipette was used to puncture a cell, collect sample and then PFD from the second barrel is transferred to form an immiscible plug. (c) Mass spectrum of a red Allium cepa cell.

Scanning electrospray microscopy (SESM)

Electrospray from nanopipettes is used to realize a new mode of scanning probe microscopy, termed scanning electrospray microscopy. Electrospray current, which is dependent on the distance between the emitter and surface, is used as a feedback mechanism for topographical imaging. SESM provides an ambient, noncontact method to investigate sample topography and images can be generated over both conductive and insulative features. As a consequence of electrospray, scanning a surface with SESM results in deposition of salt solution on the substrate. This controlled deposition presents opportunities for application in the realm of electrodeposition, nanofabrication, and electrospinning. We are also pursuing SESM as a route to high resolution mass spectrometry imaging, with added dynamic probe-distance control and information about sample height that many mass spectrometry imaging techniques do not possess.

Figure 2. (a) Schematic of SESMscanning electrospray microscopy (SESM) setup. (b) Representative approach curves over a gold-coated glass slide at 80, 90, 100, 110, and 120V with a ~22 nm inner diameter (i.d.) pipette.



Saha-Shah, A.; Green, C.M.; Abraham, D.H.; Baker, L.A. Segmented flow sampling with push-pull theta pipettes, Analyst, 2016 (


SESM abstractYuill, E.M.; Shi, W.; Poehlman, J.; Baker, L.A. Scanning electrospray microscopy from nanopipettes, Anal. Chem., 2015, 87, 11182-11186. (


Graphical abstract: Nanopipettes: probes for local sample analysisSaha-Shah, A.; Weber, A.E.; Karty, J. A.; Ray, S. J.; Hieftje, G. M.; Baker,  L. A.Nanopipettes: probes for local sample analysis, Chem. Sci., 20156, 3334-3341. (


pimsYuill, E.M.; Sa. N.; Ray, S.J.; Hieftje, G.M.; Baker, L.A. Electrospray ionization from nanopipette emitters with tip diameters of less than 100 nanometers, Anal. Chem., 2013, 85, 8498-8502. (