About CE-MS Interface Development

The field of CE-MS coupling is currently rapidly evolving. The established co-axial sheath solvent flow electrospray ionization interface method as introduced by Agilent Technologies (before Hewlett-Packard) is challenged by new sheathless or extremely low sheath flow sprayers published by Moini et al, Chen et al, Dovichi et al and Smith et al. with putative higher sensitivity. These novel approaches though are not yet offered commercially in a coherent, complete CE-MS system as Agilent Technologies does.

Agilent is challenging these competitive, new CE-MS coupling methods by improving all components of their current approach from the CE, the sprayer, and the MS to the software controlling the overall system rendering their system robust, reliable, and comparatively sensitive. Moreover, an extensive library of CE-MS AppNotes and a guidebook "CE/MS Principles and Practices, a guidebook for novices and practitioners" has been published. These exciting developments will eventually benefit all users and deliver a compelling argument for using CE as a separation technique for chemical analysis and bio-analytical measurements.

Coupling HPLC Separations with MS Detection

Since HPLC grew into maturity in the early eighties, coupling with mass spectrometry has been a challenge. Bringing the analytes out of the liquid phase, ionizing them, and transferring the molecular ions into the ultra-high vacuum, is far more difficult in HPLC than in the case of gas phase separations (GC-MS). After multiple iterations in interfacing methodology, e.g., by transport of the column eluate via a moving belt or moving wire into the vacuum, by direct liquid inlet introduction ¹, by thermo-spray ionization², by particle beam ionization approaches³ or by offline coupling via MALDI plates, electrospray ionization (ESI) at atmospheric pressure (AP) has become established as the de facto standard interfacing method since >20 years.

Initial Work to Interface CE with a mass spectrometer

Several approaches to couple CE with MS were reported in the late eighties. These can be divided into three different approaches:

1. direct spray with metal or metalized needle for electrical contact
2. liquid junction interface where the BGE in the capillary is hydraulically connected to a reservoir where electrical contact is present
3. co-axial sheath flow interface where a conductive solvent flows around the outside of the CE capillary and provides a hydraulic connection to an electrical contact

Smith⁸ , Banks⁹ , Vouros¹⁰, Chen and Maxwell¹¹ have described the early developments of CE-MS in comprehensive reviews.

Ion spray interface for CE-MS

In analogy to the development of pneumatically assisted ESI by Henion et al. (Ion spray) this group applied the ion spray for CE-MS coupling¹⁷. In a major part of their early work, the group used a liquid junction approach e.g. described in US Patent 4994165 (1991, figures taken from this patent) or in later work described in reference 16 on the previous page.

Coaxial Sheath Solvent Ion Spray Interface - 1

Thibault and coworkers deserve the credit for being the first to combine the coaxial sheath solvent concept from the Smith group at Pacific Northwest National Laboratory with the ion spray approach of Henion and coworkers from Cornell University. Below their interface is depicted¹⁸,¹⁹.

Coaxial Sheath Solvent Ion Spray Interface - 2

The Henion group describes an coaxial sheath solvent interface with pneumatically assisted spray formation²⁰,²¹. Details of the interface were provided in the second paper.

Coaxial Sheath Solvent Ion Spray Interface - 3

An important contribution to development of the coaxial sheath solvent ion spray interface came from Banks. All the designs described before applied the electrospray voltage to the spray needle and are grounded through the spray with the mass spectrometer entrance. Banks noted that this approach has two essential disadvantages^22,23.

• The CE column exit must be floated at the required ES potential (several kV)  causing the resulting electric field applied to the CE capillary to be the difference between the applied CE voltage and the ES voltages.
• If the ES voltage is applied during the injection phase, the sample constituents loaded on the capillary will tend to migrate back out of the capillary entrance by a reverse EOF that is generated by the ES voltage.