Simple chip-based interfaces for on-line monitoring of supramolecular interactions by nano-ESI MS

Abstract

Two simple interfaces were designed and realized, enabling on-line coupling of microfluidics reactor chips to a nanoflow electrospray ionization (NESI) time-of-flight (TOF) mass spectrometer (MS). The interfaces are based on two different approaches: a monolithically integrated design, in which ionization is assisted by on-chip gas nebulization, and a modular approach implying the use of commercially available Picospray tips. Using reserpine as a reference compound in a 1ratio1 mixture of acetonitrile and water revealed that both interfaces provide a remarkably stable mass spectrometric signal (standard deviations lower than 8% and 1% for the monolithic and modular approaches, respectively). Glass microreactors, containing mixing zones, were fabricated and coupled to the modular interface with perfluoroelastomer Nanoport fluidics connectors, providing a tool to study chemical reactions on-line. Investigation of the mixing dynamics showed that complete on-chip reagents mixing is achieved within a few tens of milliseconds. Metal-ligand interactions of Zn-porphyrin with pyridine (2), 4-ethylpyridine (3), 4-phenylpyridine (4), N-methylimidazole (5), and N-butylimidazole (6) in acetonitrile as well as host-guest complexations of beta-cyclodextrin (7) with N-(1-adamantyl)acetamide (8) or 4-tert-butylacetanilide (9) in water were studied by mass spectrometry using the modular NESI-chip interface. From on-chip dilution-based mass spectrometric titrations of Zn-porphyrin 1 with pyridine (2) or 4-phenylpyridine (4) in acetonitrile Ka-values of 4.6 +/- 0.4 x 10(3) M(-1) and 6.5 +/- 1.2 x 10(3) M(-1), respectively, were calculated. The Ka-values are about four times larger than those obtained with UV/vis spectroscopy in solution, probably due to a higher ionization efficiency of complexed compared to uncomplexed Zn-porphyrin. For the complexation of N-(1-adamantyl)acetamide (8) with beta-cyclodextrin (7), a Ka-value of 3.6 +/- 0.3 x 10(4) M(-1) was obtained, which is in good agreement with that determined by microcalorimetry.

Fabrication, mechanical testing and application of high-pressure glass microreactor chips

“…When microfluidic chips made of silicon-glass or quartz are positioned in this type of clamp-holders or similar support units, reliable sealing pressures of 50-150 bar can be obtained [16,17]. Alternative to this are connections of standard capillary tubing to microfluidic chips using (non-)epoxy based adhesives (∼2 bar; permanent connection) [18,19], PDMS casting techniques (3 bar; permanent) [20], in situ melting and epoxy glueing (21 bar; permanent) [21] or PEEK interfaces with NanoPort TM assembly tools in combination with home-built chip holders (up to ∼100 bar, non-permanent) [22][23][24].…”

Polymeric-Based In Vitro Diagnostic Devices

“…Low dead volume fluidic interfaces with glass and siliconbased chips rely on modifications to the variety of manifold assemblies [137][138][139].…”

Nano-capillary electrophoresis for environmental analysis

“…Currently, mass spectrometer chip-based detectors can be coupled with nano-capillary electrophoresis, leading to quite good sensitivities. Some reviews (Brivio et al 2005;Chen et al 2006;Garcia and Henry 2007;Kitagawa and Otsuka 2011;Lazar et al 2006;Stachowiak et al 2004;Xu and Baba 2004;Zamfir 2007) are appeared in the literature on detection in nano-capillary electrophoresis. These describe various advancements, hyphenations and working capacities.…”

“…Interestingly, future of these detectors was predicted well by the authors. Brivio et al (2005) reported supramolecular nano flow electrospray ionization on chip, providing good sensitivity. Chen et al (2006) reviewed electrochemical detection for monitoring the environmental pollutants.…”