Thursday, December 16, 2021

Leading the Way to the Future of GC-MS


The new book by Professor Aviv Amirav, titled "Gas Chromatography-Mass Spectrometry with Cold EI: Leading the Way to the Future of GC-MS" explores this revolutionary technology in depth.

Book abstract:

Gas chromatography-mass spectrometry (GC-MS) with supersonic molecular beams (SMB) (also named GC-MS with Cold EI) is based on GC and MS interface with a SMB and on the electron ionization (EI) of vibrationally cold analytes in the SMB (hence the name Cold EI) in a contact-free fly-through ion source.

Cold EI improves all the central GC-MS performance aspects and brings a broad range of important benefits thereby leading the way to the future of GC-MS. Cold EI provides enhanced molecular ions combined with effective library-based sample identification. Sample identification is further improved by the use of powerful TAMI software that is based on isotope abundance analysis and improved quadrupole mass accuracy for the provision of the sample elemental formula from its molecular ion group of isotopologues. The range of low volatility, polar and thermally-labile compounds amenable for analysis is significantly increased via the use of a contact-free fly-through ion source and the ability to lower sample elution temperatures through the use of high column carrier gas flow rates. Effective fast GC-MS is enabled particularly due to the possible use of high column flow rates, column flow programming and improved system selectivity in view of the enhancement of the molecular ions. 

GC-MS with Cold EI is characterized by low limits of detection (LOD) and identification (LOI) that are superior to that of GC-MS with standard EI, particularly for sample compounds that are difficult to analyze. Cold EI is further characterized by uniform compound independent response for improved quantitation and it can serve as a non-targeted full-scan alternative to MS-MS since the selectivity on the molecular ion is improved. 

The ion source of GC-MS with Cold EI is inherently inert and further characterized by fast response and vacuum background filtration capability. The same ion source offers four modes of ionization including Cold EI, Low eV Soft Cold EI, Classical EI and Cluster Chemical Ionization. Mode changing is via a simple method change without any hardware change and requires only several seconds. Thus, with Cold EI there is no need for any other ion source. 

The GC separation of GC-MS with Cold EI can be improved with pulsed flow modulation GCxGC-MS. Electron ionization LC-MS with Cold EI can also be combined with the GC-MS with Cold EI in one MS system, with fast and easy switching between these two modes of operation. 

A range of applications is described with emphasis on those that are unique to or that are much better analyzed by GC-MS with Cold EI.

Book Content
  • Abstract
  • 1. Background
  • 2. Experimental—The GC-MS with Cold EI Systems
  • 3. Cold Electron Ionization (Cold EI)
  • 4. Sample Identification via Its Cold EI Mass Spectrum by the NIST library 
  • 5. Cold EI versus Low Electron Energy EI
  • 6. Classical EI with the SMB System
  • 7. Isotope Abundance Analysis (IAA) for the Provision of Elemental Formulae from Cold EI Mass Spectra
  • 8. Isomer Mass Spectral Effects and Isomer Distribution Analysis
  • 9. Improved Sample Identification via Its Cold EI Mass Spectrum
  • 10. Cluster Chemical Ionization with SMB
  • 11. Extending the Range of Compounds Amenable for Analysis—Healing the Achilles Heel of GC-MS
  • 12. Uniform Compound Independent Ion Source Response and Its Benefits
  • 13. Sensitivity and Limits of Detection
  • 14. Speed—Fast GC-MS with Cold EI
  • 15. Pulsed Flow Modulation Comprehensive Two Dimensional GCxGC-MS with Cold EI
  • 16. Enhancement Technologies for GC-MS with Cold EI
  • 17. Hyperthermal Surface Ionization
  • 18. ChromatoProbe Sample Introduction Device
  • 19. Low Thermal Mass Fast GC for Ultra-Fast GC-MS
  • 20. Open Probe Fast GC-MS—Real Time Analysis with Separation and Library Identification
  • 21. Electron Ionization LC-MS with Cold EI and GC-MS and LC-MS in One MS System
  • 22. GC-MS-MS with Cold EI
  • 23. Photoionization of Cold Molecules in SMB (Cold PI)
  • 24. GC-MS with Cold EI Maintenance, Flexibility, Ease of Use and Price
  • 25. Selected Applications of GC-MS with Cold EI
  • 26. Hydrocarbons Analysis
  • 27. Organic Chemistry Service Analysis
  • 28. Oil Analysis for Its Diglycerides and Triglycerides Content
  • 29. Lipids in Human Blood Analysis for Medical Diagnostics
  • 30. Beeswax Analysis and the Challenge of Material Identification
  • 31. Forensic and Homeland Security Explosives Analysis
  • 32. Cannabis and Cannabinoids Analysis
  • 33. Drugs Impurities Analysis
  • 34. Pesticides Analysis in Agricultural Products
  • 35. Nonoxinol-9 Condom Spermicide Analysis
  • 36. Flavonoids in a Plant Extract Analysis
  • 37. Discussion and Conclusions
  • Acknowledgements
  • Epilogue
  • Bibliography

You can get the book as a pdf file for free by emailing your request to Professor Amirav at:  Please describe in your Email the reason for your interest in Cold EI  

You can also purchase the book from Scientific Research Publishing at:

Sunday, September 12, 2021

8270 Mixture Analysis by GC-MS with Cold EI


Aviv Amirav, Tel Aviv University and Aviv Analytical. 


The United States Environmental Protection Agency method 8270 is one of the most widely used GC-MS analysis. It lists over 250 semivolatile compounds and usually GC-MS methods are developed around the analysis of available 8270 mixtures such as the Restek MegaMix with 76 compounds. 

In this study we demonstrate and discuss this mixture analysis by GC-MS with Cold EI. We show that GC-MS with Cold EI can easily perform this analysis and with several important benefits of faster analysis of 10 minutes, complete elimination of ion source peak tailing even for compounds such as pentachlorophenol, benzidine and large PAHs and the provision of enhanced molecular ions while retaining NIST library identification. Thus, GC-MS with Cold EI is the best tool for environmental analysis that generates the greatest amount of sample and matrix information. 

Thursday, May 2, 2019

The Multiple Benefits of Cold EI – Leading the Way to the Future of GC-MS

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

GC-MS is characterized by many performance aspects and most of them are not mentioned or discussed by the GC-MS vendors and/or by any user's paper. The purpose of this paper is to list 72 such performance parameters and discuss how Cold EI improves the vast majority of them. GC-MS with Cold EI is based on a GC and MS interface with a Supersonic Molecular Beam (SMB) and on electron ionization of sample compounds while they are vibrationally cold in the SMB (thus named Cold EI) in a contact-free fly-through ion source.

Cold EI Improves all the central GC-MS performance aspects, including: identification, mass spectral information, range of compounds that are amenable for analysis, sensitivity (detection limits), speed of analysis, and response uniformity.

Eight categories of GC-MS performances are listed below and in each of them we have several sub categories (given in the number in bracket):    
  1. Improved sample identification (13).
  2. Extending the range of compounds amenable for GC-MS analysis (3).
  3. Speed – faster GC-MS analysis (9).
  4. Sensitivity (12).
  5. Uniform, compound independent ion source response, quantitation and reproducibility (4).
  6. Improved compatibility with GC-MS enhancement technologies (11).
  7. Improved GC-MS maintenance, flexibility, ease of use and price (15).
  8. Improved utilization of mass analyzer specifications (5).  
Quoting Aristotle "The whole is greater than the sum of its parts", this combination of so many improvements (>60) creates a new and qualitatively superior technology that actually improves every type of analysis. While GC-MS with Cold EI enables new type of analyses and significantly improves challenging analyses, it does not impede on any simple method of analysis (compared with standard EI). Consequently, GC-MS with Cold EI is leading the way to the future of GC-MS. 

Tuesday, January 1, 2019

GC-MS with Cold-EI Demonstration Video

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

In this video we demonstrate a live analysis of a test mixture, showing how the Cold EI technology improves all the central performance aspects of GC-MS. The test mixture includes 1 ng on-column each n-C16H34, methylstearate, cholesterol and n-C32H66 plus 10 pg OFN, and via its analysis we demonstrate twelve unique benefits of GC-MS with Cold EI.

Have a happy new year

Monday, December 24, 2018

Classical EI-SMB Ion Source and its Comparison with Classical EI with High Efficiency Source

Aviv Amirav, Tel Aviv University and Aviv Analytical Ltd.

Executive Summary

GC-MS with Cold EI includes, among its several benefits, a classical EI mode of operation. Mode changing is uniquely achieved in a few seconds via a click of the mouse method change that involves the reduction of the helium make-up cooling gas flow rate without touching any hardware. Classical EI with the Cold EI contact-free fly-through ion source (named Classical EI-SMB) provides classical EI mass spectra with high NIST library matching factors and identification probabilities. Furthermore, in comparison with the various other standard EI ion sources, Classical EI-SMB excels in having a contact-free fly-through ion source structure and as a result: a) It exhibits uniform compound independent response; b) It has no ion source peak tailing thus preserves the chromatographic separation; c) It is an inherently inert ion source thus it extends the range of compounds amenable for analysis via the analysis of polar and labile compounds such as free fatty acids and/or amides without derivatization; d) It has much lower noise and thus exhibits very high total ion count mass chromatograms signal to noise ratio. Classical EI-SMB is compared in this article with the Agilent 5977B with high efficiency ion source (HES) and all the above written benefits are demonstrated.   

Monday, December 17, 2018

Achieving the Lowest Limits of Identification – GC-MS with Cold EI versus Standard EI with High Efficiency Source

Aviv Amirav, Tel Aviv University and Aviv Analytical Ltd.

Executive Summary  

GC-MS sensitivities are specified with octafluoronaphthalene (OFN). However, for many GC-MS users the most important operational parameter is the sample limits of identification. We compared the Aviv Analytical GC-MS with Cold EI with the Agilent 5977B GC-MS with high efficiency ion source (HES) in sample identification. We found that Cold EI far outperforms the 5977B-HES in both detection and identification limits. Cold EI detected and identified thirteen impurity compounds in a given test mixture while the HES standard EI failed to detect most of these impurities and failed to identify any of them. In this article we demonstrate and discuss several Cold EI benefits of superior sensitivity, better identification capability, greater range of compounds amenable for analysis and faster speed of analysis. The graphical abstract figure above demonstrates the absence of impurity peaks in the TIC with HES versus at least thirteen detected peaks in Cold EI in which each peak exhibits a molecular ion and is amenable for trustworthy identification.   

Thursday, October 11, 2018

Permethrin Drug Impurity Analysis with GC-MS with Cold EI and the Road to Failure in Such Analysis by GC-MS with Standard EI

Aviv Amirav, Tel Aviv University and Aviv Analytical


A Permethrin impurity was successfully analyzed by GC-MS with Cold EI after it failed to be analyzed by GC-MS with standard EI. In this application note we demonstrate and discuss the ways GC-MS with standard EI analysis of relatively large compounds gradually becomes more difficult as the sample compound size is increased due to reduced total ion count signal, reduced molecular ion relative abundance and increased noise. Accordingly, as the analyzed sample compound becomes larger its GC-MS analysis becomes harder in a gradual fashion until it fails. In contrast, GC-MS with Cold EI can analyze twice larger compounds and thus significantly extends the range of compounds amenable for GC-MS analysis.    

Thursday, June 14, 2018

Cold EI Versus Low Electron Energy EI

Aviv Amirav, Tel Aviv University and Aviv Analytical

Executive Summary
Recently, the use of low electron energy electron ionization is claimed to serve as a soft ionization method and it is sometimes referred to as "Soft EI". In this application note, we show and discuss that low-eV EI is not a universal soft ionization method, its applicability is limited to small molecules that exhibit molecular ions in 70 eV EI, and its enhancement of molecular ion abundances is small or non-existent for many compounds. Furthermore, the addition of a 2nd analysis and loss of signal with low eV EI rarely justify its use in real-world applications.

In contrast, Cold EI (electron ionization of cold molecules in supersonic molecular beams) is a far superior "Soft EI" ion source with close to universal applicability. We demonstrate that for squalane (C30H62), the molecular ion is the base peak in the 70 eV Cold EI mass spectrum, which is 10,000-fold higher than its 0.01% relative ion abundance in 14 eV low electron energy EI. Furthermore, Cold EI is the best ion source in all other main performance aspects, and most importantly, it significantly increases the range of compounds and applications amenable for analysis. Thus, Cold EI bridges the GC-MS gap with LC-MS and can increase the total GC-MS market.

Tuesday, June 12, 2018

Lipids in Human Serum Analysis by the 5975-SMB GC-MS with Cold EI

Aviv Amirav and Svetlana Tsizin, Tel Aviv University and Aviv Analytical, Tel Aviv Israel. 
Gabi Shefer, Ichilov hospital Tel Aviv Israel 

Cholesterol and triglycerides analysis in human blood is among the most widely used chemical medical diagnostics tests. Some estimate the number of such analysis at 1 Billion/year with cost of about $30 for each analysis (three analyses of cholesterol LDL, HDL and triglycerides at $10 each). Thus, the total lipids in blood analysis market is about $30 Billion/year. However, current analysis brings limited information and mass spectrometry can provide far better and more detailed lipids in blood information if an appropriate instrument for such analysis will be available. We used our GC-MS with Cold EI and demonstrated as below the analysis of large range of lipids in blood. Each analysis provided information on the amount of several free fatty acids, cholestadiene, cholesterol, vitamins E and 25 Hydroxy vitamin D3 and many diglycerides, cholesteryl esters and triglycerides. Notably, we can clearly distinguish differences among samples from different people. Each analysis took only 10 min via the use of column flow programing. Our results yielded extensive lipidomics information that may include new diagnostic tools. We feel that this new and advantageous assay for lipids profiling in blood is worthy of further investigation and evaluation.  

Tuesday, June 5, 2018

Impurities Analysis in Active Pharmaceutical Ingredients Comparison of Cold EI with Standard EI

Aviv Amirav, Tel Aviv University and Aviv Analytical, Tel Aviv Israel.


Active pharmaceutical ingredients (APIs) in drug formulations need to have impurity levels < 0.1% according to the FDA or else the impurities need to be characterized via lengthy and expensive clinical toxicology procedures. Current impurities in APIs are typically analyzed by LC-MS. However, such LC-MS analysis is confronted by ion suppression effects for impurities that elute near the API, non-polar impurities are not ionized, those impurities that are discovered exhibit mostly protonated molecular ions without structural information and since Electrospray LC-MS has highly non-uniform ionization yields there is no information on the concentration of the discovered impurities. Thus, those API impurities that are observed need to be fully identified, synthesized and follow compound specific concentration calibration.

GC-MS with Cold EI is ideal for analysis of API impurities because:
  • It has uniform compound independent response, thus detected impurity concentrations can be assessed, and those below 0.1% can be neglected 
  • It often provides EI-based library identification, which is usually improved by the presence of an enhanced molecular in Cold EI plus structural information from the full display of fragment ions 
  • Cold EI ionizes non-polar as well as polar analytes 
  • It does not suffer from any ion suppression effects 
  • Total ion mass chromatograms in Cold EI often provides greater sensitivity than ESI-LC-MS 
  • Cold EI has much greater range of compounds amenable for analysis than any other GC-MS. 
Thus, Cold EI seems ideal for API impurities analysis.