Potential of On-Line CIMS for Bioprocess Monitoring

Abstract

Chemical-ionization mass spectrometry (CIMS) using flow reactors is an emerging method for on-line monitoring of trace concentrations of organic compounds in the gas phase. In this study, a flow-reactor CIMS instrument, employing the H(3)O(+) cation as the ionizing reagent, was used to simultaneously monitor several volatile metabolic products as they are released into the headspace during bacterial growth in a bioreactor. Production of acetaldehyde, ethanol, acetone, butanol, acetoin, diacetyl, and isoprene by Bacillus subtilis is reported. Ion signal intensities were related to solution-phase concentrations using empirical calibrations and, in the case of isoprene, were compared with simultaneous gas chromatography measurements. Identification of volatile and semivolatile metabolites is discussed. Flow-reactor CIMS techniques should be useful for bioprocess monitoring applications because of their ability to sensitively and simultaneously monitor many volatile metabolites on-line.

A method for measuring enthalpy of volatilization of a compound, ΔvolH, from dilute aqueous solution

“…Like several other chemical ionization mass spectrometry techniques,16–20 SIFT‐MS analysis is based on the following equation from which the gas‐phase mixing ratio of a compound in air, [ M ] g (in ppb or ppm), can be determined:21–24 where [ M ] ft is the reactant molecule number density in the flow tube, I and i are the precursor and product ion count rates, k is the rate coefficient of reaction between the precursor ion and the compound M, and t is reaction time. A is a coefficient converting [ M ] ft to [ M ] g and is determined by systematic parameters: pressure and temperature of the carrier gas in the flow tube, flow rates of the carrier gas and sample air 22.…”

“…Recently, several techniques utilizing the combination of chemical ionization and mass spectrometry15 have been successfully developed 16–24. Examples of these are proton transfer reaction mass spectrometry (PTR‐MS),16, 17 negative ion chemical ionization mass spectrometry (NI‐CIMS) and chemical ionization mass spectrometry (CIMS),18, 19 and selected ion flow tube mass spectrometry (SIFT‐MS) 21–24. They have been used to obtain the HLC of volatile compounds, and to study HLC dependencies on temperatures and on the salt content in water 16–18, 23, 24.…”

“…Examples of these are proton transfer reaction mass spectrometry (PTR‐MS),16, 17 negative ion chemical ionization mass spectrometry (NI‐CIMS) and chemical ionization mass spectrometry (CIMS),18, 19 and selected ion flow tube mass spectrometry (SIFT‐MS) 21–24. They have been used to obtain the HLC of volatile compounds, and to study HLC dependencies on temperatures and on the salt content in water 16–18, 23, 24. Δ vol H values for ethanol, acetaldehyde and acetone were actually obtained from HLC measured at 25°C and 40°C in a previous SIFT‐MS study 23…”

“…However, in these methods measuring HLC and Δ vol H ,7–12, 16–18, 23, 24 the sampling and analytical procedures were usually time‐ and labour‐consuming as at least four different standard solutions were needed to measure HLC at each temperature 10. For more accurate analysis four or five independent solutions of each concentration are required 9.…”

Implementation of proton transfer reaction‐mass spectrometry (PTR‐MS) for advanced bioprocess monitoring

“…On‐line mass spectroscopic techniques show excellent sensitivity and time resolution and require no pre‐concentration or sample preparation steps. To cope with the complexity of the VOC matrix of bioprocesses, soft ionization techniques like chemical ionization mass spectrometry that allow compound ionization virtually without fragmentation can be used (Custer et al, 2003). Membrane inlet‐based VOC sampling systems either directly connected to the high‐vacuum regime of a mass spectrometer or acting indirectly via a carrier gas are employed (Bastidas‐Oyanedel et al, 2010; Hansen et al, 1994).…”