Wednesday, May 27, 2015

How Enhanced Molecular Ions in Cold EI Improves Sample Identification by the NIST Library


Tal Alon (1,2)  and Aviv Amirav (1,2)

1. School of Chemistry, Tel Aviv University, Tel Aviv 69978 Israel.
2. Aviv Analytical LTD, 3 Haarad Street, Tel Aviv 69107 Israel.

Abstract

Library based compound identification with electron ionization (EI) mass spectrometry (MS) is a well-established identification method which provides sample compounds names and structures up to the isomer level. The library (such as NIST) search algorithm compares different EI mass spectra in the library's database with the measured EI mass spectrum, assigning each of them a similarity score called 'Match' and an overall identification probability.

Cold EI is electron ionization of vibrationally cold molecules in supersonic molecular beams. Cold EI provides mass spectra with all the standard EI fragment ions combined with enhanced Molecular Ions (MI) and high mass fragments. As a result, Cold EI mass spectra differ from those provided by standard EI and tend to yield lower matching scores. However, in most cases library identification actually improves with Cold EI, as library identification probabilities for the correct library mass spectra are increased, despite the lower matching factors.

This research examines the way enhanced molecular ion abundances affect library identification probability and the way Cold-EI mass spectra, which include enhanced molecular ions and high mass fragments, typically improve library identification results. It describes the results of several computer simulations, which incrementally modified the relative abundance of the various ions and analyzed the resulting mass spectra. The simulation results support previous measurements, showing that while enhanced molecular ion and high mass fragments lower the matching factor of the correct library compound, the matching factors of the incorrect library candidates are lowered even more, resulting in a rise of the identification probability for the correct compound. This behavior which was previously demonstrated by analyzing Cold-EI mass spectra occurs because high mass ions, and especially the molecular ion, characterize a compound more than low mass ions and therefore carry more weight in library search identification algorithms. 

Keep reading to find out how the Aviv Analytical 5975-SMB GC-MS with Cold EI uniquely enables the combination of enhanced molecular ion and improved NIST library based sample identification.

Wednesday, May 13, 2015

Soft Cold EI – Approaching Molecular Ion Only with Electron Ionization





Aviv Amirav (1,2), Uri Keshet (1) and Albert Danon (3) 
1. School of Chemistry, Tel Aviv University Tel Aviv 69978 Israel
2. Aviv Analytical LTD, 3 Haarad Street Tel Aviv 69107 Israel
3. Nuclear Research Center Negev P.O. Box 9001 Beer Sheva Israel  

Introduction  

GC-MS with Cold EI (Electron Ionization of Cold Molecules in Supersonic Molecular Beams) provides ideal EI mass spectra which combine the usual library searchable EI fragments with enhanced molecular ions for improved library based identification probability, improved confidence in the sample identity and improved sensitivity and selectivity in the sample analysis. However, in some cases such as in the analysis of complex petrochemical matrices a soft ionization method that provides only molecular ions is desirable since it can generate carbon number distributions for petroleum homologues and since mass spectra with molecular ions only add a dimension of separation that can supplement and complement that of the GC. Field ionization is an example of a soft ionization method that can be combined with GC-MS in which the MS adds another independent dimension of information hence it was named GCxMS (F. C. Y Wang, K. Qian and L. A Green, Anal. Chem. 77, 2777-2785 (2005)). However, field ionization is three orders of magnitude less sensitive than EI, it is incompatible with library based identification, its response can be compound dependent and it may exhibit peak broadening/tailing. While 70 eV Cold EI provides the ideal mass spectra one can use the same fly-through Cold EI ion source at low electron energies in an attempt to observe molecular ion alone. Contrary to some perceptions, for most compounds lowering the electron energies does not affect much the observed EI mass spectra due to electron induced excitation of high lying vibrational states of the ions even at low electron energies. However, hydrocarbons are an example of compounds class that their EI mass spectra are relatively largely affected by the electron energy, and in Cold EI the elimination of internal heat amplifies the low electron energy effect. 

We tested low electron energy Cold EI a few times in the past and although the molecular ion was the dominant MS peak we failed to eliminate the fragment ions and get molecular ion only. Thus, we decided to further investigate the reasons for our inability to get molecular ions only. We found that once the sample compound is cooled by the supersonic expansion it can be reheated via reflected scattered helium atoms near the skimmer. Furthermore, once a labile molecular ion is formed it can undergo undesirable collision induced dissociation (CID) the same as in MS-MS, and the magnitude of such CID can be significant for labile molecular ions such as of hydrocarbons. In order to reduce these adverse effects we evaluated the effect of reduction of helium pressure at the ion source and MS vacuum chamber via the increase of the nozzle-skimmer distance. We found out that this increased nozzle-skimmer distance resulted in noticeable increase of the ratio of molecular ions to low mass fragment ions.   

Keep reading to find out how the Aviv Analytical 5975-SMB GC-MS with Cold EI uniquely improves low electron energy Cold EI and converts it into a Soft Cold EI while further approaching the ideal of molecular ion only ionization method.

Monday, December 15, 2014

Open Probe Fast GC-MS - Real Time Analysis with Separation


Uri Keshet (1), Tal Alon (1,2) , Alexander B. Fialkov (1), and Aviv Amirav (1,2) 
1.   School of Chemistry, Tel Aviv University, Tel Aviv 69978, Israel.  
2.   Aviv Analytical Ltd, 3 Haarad Street, Tel Aviv 69107, Israel  

Abstract 

An Open Probe inlet was combined with a low thermal mass (LTM) ultra fast gas chromatograph (GC) and a mass spectrometer (MS) of a standard GC-MS for obtaining real time analysis with separation. The Open Probe is based on a vaporization oven that is open to room air with an addition of helium purge flow protection that eliminates air leakage into the oven, column and MS ion source. Sample introduction into the Open Probe is as simple as; touch the sample, insert the sample holder into the open probe oven and have the results in 30 s with under a minute ready for next analysis. 
The Open Probe Fast GC-MS revolutionizes the field of real time analysis as it provides several major benefits in comparison with DART, DESI and other ambient ionization methods or MS probes:
  • GC separation,
  • Library identification
  • Absence of ion suppression effects
  • Uniform electron ionization response for improved quantitation
  • Uses a low cost quadrupole MS (of GC-MS). 
Watch the short video below and keep reading to find out more about the new Open Probe fast GC-MS which was combined with Agilent 7890B GC and 5977 MS and learn about its several demonstrated application and benefits. 



Thursday, May 8, 2014

Linearity, Sensitivity and Response Uniformity Comparison of the Aviv Analytical 5975-SMB with Cold EI and the Agilent 5977A GC-MS with Standard EI





















Aviv Amirav (1,2), Uri Keshet (1) and Bogdan Belgorodsky (1) 
1.   Tel Aviv University 
2.   Aviv Analytical Ltd 

Introduction 

Standard GC-MS analysis of low volatility and polar compounds is known to be plagued by ion source related peak tailing and degradation (see our post on peak tailing here). We found that these intra ion source tailing and sample degradation effects strongly depend on the sample concentration. Consequently, when these compounds are analyzed, the response of the standard EI ion source of GCMS is both non-uniform and non-linear. In this article we evaluate and compare the Aviv Analytical 5975-SMB GC-MS with Cold EI with the new Agilent 5977 Extractor GC-MS in the analysis of a test mixture containing five components, using the same on-column amounts. In contrast to the Agilent 5977 the Aviv Analytical 5975-SMB GC-MS with Cold EI exhibits uniform, linear, compound independent response. We concluded that the harder the compound analysis the greater is the sensitivity gain of the 5975-SMB over 5977 extractor with standard EI, up to and over a factor of 100.

Keep reading to find out how the Aviv Analytical 5975-SMB GC-MS with Cold EI uniquely enables uniform and linear ion source response with a substantial improvement of sensitivity in comparison with a state of the art GC-MS with standard EI.

Wednesday, December 18, 2013

Explosives Analysis with the 5975-SMB GC-MS with Cold EI
















Aviv Amirav, Professor of Chemistry at Tel Aviv University and Director - Aviv Analytical Ltd, December 4, 2013.

Introduction

Effective explosives analysis is very important for homeland security and forensic applications. However, explosives analysis is challenging and the number of explosive compounds that require monitoring is growing with time. Furthermore, the growing use by terrorists of peroxide explosive compounds such TATP (triacetone triperoxide, C9H18O6) and HMTD (Hexamethylene triperoxide diamine, C6H12N2O6) implies that modern analytical techniques of explosive analysis must be as effective with peroxide explosive as with the traditional poly nitro explosives. In fact, there is no limit to the desirable LOD and selectivity of explosives analysis but these features must be combined with an analytical system that enables the analysis of the entire explosives family used by terrorists. We note that the actual system sensitivity and selectivity should be measured by its performance with the most difficult to analyze explosives such as the peroxide explosives and not with TNT and alike. 

Keep reading to find out how the Aviv Analytical 5975-SMB GC-MS with Cold EI uniquely enables the sensitive analysis of the full range of explosive compounds including TATP, HMTD, R-Salt, TNT, ETN, PETN, RDX, Tetril, HMX and Urea Nitrate while providing abundant molecular ions or high mass fragments that improve the detection selectivity and identification capability of these labile compounds.

Wednesday, November 20, 2013

Deuterium Exchange Analysis for Improved Structural Elucidation with the 5975-SMB GC-MS with Cold EI


Aviv Amirav, Professor of Chemistry at Tel Aviv University and Director - Aviv Analytical

Introduction

Hydrogen-Deuterium exchange (also called H-D or H/D exchange) is a chemical reaction in which hydrogen atoms that are bound to nitrogen or oxygen atoms (possibly sulfur) are exchanged with deuterium atoms of certain deuterated solvents such as deuterated methanol (CD3OD or CH3OD) or heavy water (D2O). Deuterium exchange reactions followed by mass spectrometry analysis provide valuable structural information since these reactions are usually selective: only hydrogen atoms that are bound to nitrogen or oxygen atoms (such as in amines or alcohols) are exchanged with deuterium while other hydrogen atoms are unaffected. Consequently, the mass shift of the molecular ion reveals the number of OH and NH bonds in the explored compound which helps in its structural elucidation. Currently, deuterium exchange experiments are limited to NMR and LC-MS and it is practically ignored in GC-MS since:  
  1. most of the small compounds that are amenable for GC-MS analysis can be fully identified by the available extensive EI libraries.
  2. large compounds on the GC-MS scale are often incompatible with GC-MS analysis and/or do not exhibit molecular ions in their EI mass spectra.
  3. While the compound of interest may exchange its labile hydrogen atoms with deuterium, reversed exchange may occur at the GC liner, long column and particularly at the ion source metal surfaces that quickly react with ever-present water in the mass spectrometer vacuum chamber.
We found that the use of GC-MS with Cold EI uniquely enables the monitoring of deuterium exchange reactions and thus with it deuterium exchange can serve as an additional effective tool for improved structure elucidation of unknown compounds.                       

Keep reading for more information on deuterium exchange monitoring using the Aviv Analytical 5975-SMB GC-MS with Cold EI, including two analysis examples of Quinine and 17β-estradiol that serve for the validation of their structure and number of labile OH hydrogen atoms.

Monday, October 14, 2013

Pesticide Analysis by Pulsed Flow Modulation GCxGC-MS with Cold EI – An Alternative to GC-MS-MS


Uri Keshet (1), Tal Alon (1), Paulina Goldshlag (2) and Aviv Amirav (1)
1. School of Chemistry, Tel Aviv University, Tel Aviv, Israel. 
2. Israel Plant Protection and Inspection Services, Beit Dagan, Israel.
3. Aviv Analytical LTD, Tel Aviv, Israel.   

Introduction 

Pesticide analysis in agricultural products is an application area of growing importance which is usually addressed by GC-MS and LC-MS. However, pesticide analysis is confronted by the dominance of matrix interference which severely restricts the achievable limits of detection. As a result, several methods were developed and used for the reduction of matrix interference and the most widely used is MS-MS. While in LC-MS, MS-MS is practically a must in view of absence of libraries and consistent fragments in the mass spectra, in GC-MS the use of full scan possesses a few advantages of unambiguous library identification and its applicability to unlimited number of GC-MS amenable pesticides, provides however that the problem of matrix interference can be properly addressed. In addition to MS-MS at least three other techniques can be used to reduce matrix interference while enabling the use of full scan namely: a) high resolution mass spectrometry; b) GC-MS with Cold EI in which the enhanced molecular ions suppress matrix interference as described in another article in this blog. c) GCxGC-MS with its improved GC separation that can be used for the reduction of matrix interference as described in a few papers with thermal modulation and as discussed in this article.  

We developed Pulsed Flow Modulation (PFM) for obtaining GCxGC-MS with supersonic molecular beams (SMB) (also named Cold EI) based on a low cost single quadrupole mass analyzer and without any added cooling gas. For further information on the concept of Pulsed Flow Modulation GCxGC please read M. Poliak, M. Kochman and A. Amirav, "Pulsed Flow Modulation Comprehensive Two Dimensional Gas Chromatography" J. Chromatogr. A. 1186, 189-195 (2008) (also Israel patent number 176724 and USA patent number 7518103). 

In PFM-GCxGC-MS with Cold EI, sample compounds which elute from the first GC column are temporarily stored in a fused silica transfer line and are pulsed periodically injected by ~25 ml/min He gas pulse into the second column. After the pulse, ~20 ml/min He develops the chromatography in the second column for a few seconds (typically 4s). PFM is simple to construct, does not require any added gas with Cold EI and the injection time can be tuned, hence PFM-GCxGC-MS with Cold EI is enabled with quadrupole MS. The increased PFM second GC column flow rate is seamlessly handled by the Cold EI nozzle vacuum chamber.
We combined PFM-GCxGC with the Aviv Analytical 5975-SMB GC-MS with Cold EI and analyzed with it twelve pesticides in two agricultural matrices. PFM-GCxGC-MS with Cold EI combines the improved separation of GCxGC with the features of Cold EI of enhanced molecular ions and isotope information for the provision of ultimate sample identification information. Unique to PFM-GCxGC-MS with Cold EI is that in contrast to thermal modulation with standard GC-MS the second dimension elution time does not suffer from any ion source peak tailing and/or second column saturation effects and thus it is ideally suitable for pesticide analysis in complex matrices.   

Keep reading to find out how the Aviv Analytical 5975-SMB GC-MS with Cold EI enables effective pesticide analysis in agricultural matrices while using improved PFM-GCxGC separation for obtaining a major reduction of matrix interference by an average measured factor of 32. As a result, the road is open for PFM-GCxGC-MS with Cold EI to serve as an alternative to GC-MS-MS while enabling the use of full scan which is applicable to unlimited number of GC-MS amenable pesticides with improved library identification and the novel use of isotopomer ratios for pesticides identity confirmation

Monday, October 7, 2013

Pulsed Flow Modulation GCxGC-MS with Cold EI – The Emergence of Novel Concept of GCxGCxMS



Aviv Amirav, Tal Alon, Uri Keshet and Alexander Fialkov 
Tel Aviv University and Aviv Analytical

Introduction 

Comprehensive two dimensional GCxGC-MS significantly improves the separation of the GC. However, it suffers from complexity and high cost of purchase and maintenance cooling gases. In addition, with standard electron ionization the molecular ions are often weak or absent, particularly in the analysis of complex hydrocarbon mixtures. 

We developed Pulsed Flow Modulation (PFM) for obtaining GCxGC-MS with supersonic molecular beams (SMB) (also named Cold EI) based on quadrupole mass analyzer and without any added cooling gas. For further information on the concept of Pulsed Flow Modulation GCxGC please read M. Poliak, M. Kochman and A. Amirav, "Pulsed Flow Modulation Comprehensive Two Dimensional Gas Chromatography" J. Chromatogr. A. 1186, 189-195 (2008) (also Israel patent number 176724 and USA patent number 7518103). 

In PFM-GCxGC-MS with Cold EI, sample compounds which elute from the first GC column are temporarily stored in a fused silica transfer line and are pulsed periodically injected by ~25 ml/min He gas pulse into the second column. After the pulse, ~20 ml/min He develops the chromatography in the second column for a few seconds (typically 4s). PFM is simple to construct, does not require any added gas with Cold EI and the injection time can be tuned, hence PFM-GCxGC-MS with Cold EI is enabled with quadrupole MS. The increased PFM second GC column flow rate is seamlessly handled by the Cold EI nozzle vacuum chamber. 

We combined PFM-GCxGC with the Aviv Analytical 5975-SMB GC-MS with Cold EI. PFM-GCxGC-MS with Cold EI combines the improved separation of GCxGC with the features of Cold EI of enhanced molecular ions and extended mass spectral isomer and isotope information for the provision of ultimate sample information. Unique to PFM-GCxGC-MS with Cold EI is that as the second dimension elution time is increased the molecular ion mass is reduced for easier GCxGCxMS like identification. 

Keep reading to find out how the Aviv Analytical 5975-SMB GC-MS with Cold EI enables effective PFM-GCxGC-MS with Cold EI and provides ultimate level of information with an example of the analysis of JP8 jet fuel (with some Biodiesel related FAMEs). This article also describes and exposes the emergence of the novel concept of GCxGCxMS. 

Sunday, August 11, 2013

Extending the Range of Compounds Amenable for GC-MS Analysis




Aviv Amirav, Alexander B. Fialkov and Tal Alon 
Tel Aviv University and Aviv Analytical. July 22, 2013.  

Introduction

GC-MS is a powerful technique yet it suffers from a major Achilles Heel of limited range of low volatility and thermally labile compounds amenable for analysis. However, it was discovered and investigated by A. B. Fialkov, A. Gordin and A. Amirav, J. Chromatog. A.  991, 217-240 (2003) that this range can be significantly extended via two major changes in GC-MS:

  1. The use of short columns with high column flow rates and preferably with a temperature programmable injector which lowers the elution temperatures from the injector liner to the column and from the column itself (slower temperature programming rate and thinner films also help) and; 
  2. The use of a fly-through ion source in combination with sample compounds in supersonic molecular beams (Cold EI) eliminates any ion source peak tailing and/or sample degradation on the hot metallic ion source surfaces. 

The use of GC-MS with Cold EI opens the door for significantly increased range of compounds and applications that are amenable for GC-MS analysis. Consequently, GC-MS with Cold EI bridges the gap with LC-MS, helps to analyze the bottleneck hard to analyze compounds in current methods and opens the door for new and untapped opportunities in GC-MS analysis.                

Keep reading to find out how the Aviv Analytical 5975-SMB GC-MS with Cold EI uniquely enables significant extension of the range of compounds amenable for GC-MS analysis and as a result enables new types of GC-MS applications.

Thursday, July 11, 2013

Organo-Iodine Compounds Analysis by the 5975-SMB GC-MS with Cold EI


Aviv Amirav, Professor of Chemistry at Tel Aviv University and Director - Aviv Analytical
Larisa Panz Ph.D., Ksenia Kulbitski and Professor Mark Gendelman, Schulich Faculty of Chemistry at the Technion Haifa Israel. 

Introduction

Organo-iodine compounds are used in several applications, mostly as intermediates in organic synthesis because of the easy formation and cleavage of the C–I bond. The analysis of organo-iodine compounds is highly challenging since most of them are not compatible with LC-MS and electrospray ionization while in GC-MS their analysis is hampered via their possible decomposition at the GC injector, column and ion source since the iodine-carbon bond is by far the weakest among all halogen-carbon bonds. Furthermore, even if the organo-iodine compounds elute from the GC column their standard EI mass spectra are often void of any molecular ions and as a result their identification becomes impossible. Motivated by the above challenges we explored the analysis of novel synthetic organo-iodine compounds with the Aviv Analytical 5975-SMB GC-MS with Cold EI, developed a method for its successful analysis and compared the results with that obtained with GC-MS with standard EI.

Keep reading to find out how the Aviv Analytical 5975-SMB GC-MS with Cold EI uniquely enables the effective analysis of synthetic organo-iodine compounds and provides unambiguous identification of all the synthetic organo-iodine reaction mixture compounds and as a result helps optimizing the synthesis reaction conditions and yields.