Sample Injection for Real-Time Analysis (SIRTA) Using GC-MS with Cold EI.

There is a continual demand for advanced methods and instruments for real-time analysis (RTA). Most of the current RTA techniques based on MS involve ambient desorption ionization technology. However, flow injection of liquid extracted samples is another option without added modifications or cost to existing LC-MS instruments. In this work, we introduce a new RTA approach named sample injection for real-time analysis (SIRTA) using GC-MS with Cold EI. In SIRTA, the standard GC column is replaced with a 1 m long 0.1 mm I.D. fused silica capillary that connects the GC injector to the MS transfer-line of Cold EI. Thus, SIRTA with Cold EI imposes no need for any additional instrumentation; hence, it is characterized by zero added cost. Like in flow injection in MS of LC-MS, the sample is dissolved in ∼1 mL methanol or another solvent. Subsequently, the vial is placed in the GC-MS autosampler while using a standard syringe for injection without any GC separation. The analysis takes merely 0.2-0.7 min, ensuring rapid and consecutive analyses. Unlike standard EI, Cold EI enables SIRTA by taking advantage of its fly through open ion source to avoid overwhelming the ion source during the elution of solvents while still providing enhanced molecular ions for nearly all analytes. In this study, we demonstrated SIRTA Cold EI analysis of 12 compounds and 7 mixtures, including various prescription and illicit drugs, cannabis and petroleum samples, and other synthetic organic compounds including those with molecular weight up to 800 g/mol.

Fast saliva analysis by GC-MS with Cold EI and Open Probe Fast GC-MS with Cold EI for the detection of cannabis usage.

Saliva is a body fluid that is much easier to collect and analyze than blood. Thus, saliva analysis for the detection of delta 9-tetrahydrocannabinol (delta 9-THC) can serve as a tool for law enforcement agents to detect cannabis consumption by drivers. Fast saliva analysis for the presence of delta 9-THC and/or cannabidiol (CBD) is described with both gas chromatography-mass spectrometry (GC-MS) with Cold electron ionization (EI) with good separation and in 10 min and/or with Open Probe Fast GC-MS with Cold EI in under 1 min full analysis cycle time. Saliva was taken directly from donors' tongues on a thin glass rod that was used "as is" for analysis. The saliva was thermally desorbed with a modified ChromatoProbe device inside the gas chromatograph (GC) injector and in an Open Probe (Agilent name QuickProbe) for its sub-1-min analysis. Cold EI is based on coupling of the GC and mass spectrometer (MS) with a supersonic molecular beam and on EI of vibrationally cold sample molecules during their flight through a contact-free ion source (thereby named Cold EI). A revised type of Open Probe Fast GC-MS on the bench is also described. Our saliva analysis was characterized by: Saliva can be collected in the field and transported to the lab for analyses "as is" without any sample preparation. Easy detection of cannabis consumption from cigarettes and/or other cannabis products. Distinction between the isomers delta 9-THC and CBD. Ultra-fast analysis in under 1 min using Open Probe Fast GC-MS with Cold EI.

Whole blood analysis for medical diagnostics by GC-MS with Cold EI.

This study covers a new method and related instrumentation for whole blood analysis for medical diagnostics. Two-µL whole blood samples were collected using "minimal invasive" diabetes lancet and placed on a thin glass rod mounted on a newly designed BloodProbe. The BloodProbe with the whole blood sample was inserted directly into a ChromatoProbe mounted on the GC inlet, and thus, no sample preparation was involved. The analysis was performed within 10 min using a GC-MS with Cold EI that is based on interfacing GC and MS with supersonic molecular beams (SMB) along with electron ionization of vibrationally cold sample compounds in the SMB (hence the name Cold EI). Our blood analysis revealed several observations: (1) Detailed mass chromatograms were generated with full range of all the nonpolar lipids in blood including fatty acids, cholesterol, cholesteryl esters, vitamin E, monoglycerides, diglycerides, and triglycerides. (2) The analysis of whole blood was found to be as informative as the conventional clinical analysis of blood serum. (3) Cholesteryl esters were more sensitive than free cholesterol alone to the effect of diet of obese people. (4) Major enhancement of several fatty acid methyl esters was found in the blood of a cancer patient with liver dysfunction. (5) Vitamin E as both α- and ß-tocopherol was found with person-dependent ratio of these two compounds. (6) Elemental sulfur S8 was identified in blood. (7) Several drugs and other compounds were found and need further study of their correlation to medical issues.

Cold Electron Ionization (EI) Is Not a Supplementary Ion Source to Standard EI. It is a Highly Superior Replacement Ion Source.

GC-MS usually employs a 70 eV electron ionization (EI) ion source, which provides mass spectra with detailed fragment ion information that are amenable for library search and identification with names and structures at the isomer level. However, conventional EI often suffers from low intensity or the absence of molecular ions, which reduces detection and identification capabilities in analyses. In an attempt to enhance the molecular ions, several softer ion sources are being used to supplement standard EI, including chemical ionization (CI), atmospheric pressure chemical ionization (APCI), field ionization (FI), photoionization (PI), and low electron energy EI. However, the most advantageous way to enhance molecular ions is to use cold EI, which employs 70 eV EI of cold molecules in supersonic molecular beams. Cold EI yields classical EI mass spectra with highly enhanced molecular ions, which still provides high detectability and library-searchable mass spectra. In this paper, we explain and discuss why cold EI is not a supplementary ion source to standard EI, but rather it is a highly superior replacement to standard EI. With cold EI, there is no need for standard EI or any other supplemental ion source. We describe 16 benefits and unique features of cold EI that not only yield better results for existing applications but also significantly extend the range of compounds and applications amenable for GC-MS analysis.

A comparison of electron ionization mass spectra obtained at 70 eV, low electron energies, and with cold EI and their NIST library identification probabilities.

Electron ionization (EI) mass spectra of 46 compounds from several different compound classes were measured. Their molecular ion abundances were compared as obtained with 70-eV EI, with low eV EI (such as 14 eV), and with EI mass spectra of vibrationally cold molecules in supersonic molecular beams (Cold EI). We further compared these mass spectra in their National Institute of Standards and Technology (NIST) library identification probabilities. We found that Low eV EI is not a soft ionization method, and it has little or no influence on the molecular ion relative abundances for large molecules and those with weak or no molecular ions. Low eV EI for compounds with abundant or dominant molecular ions in their 70 eV mass spectra results in the reduction of low mass fragment ions abundances thereby reducing their NIST library identification probabilities thus rarely justifies its use in real-world applications. Cold EI significantly enhances the relative abundance of the molecular ions particularly for large compounds; yet, it retains the low mass fragment ions; hence, Cold EI mass spectra can be effectively identified by the NIST library. Different standard EI ion sources provide different 70 eV EI mass spectra. Among the Agilent technologies ion sources, the "Extractor" exhibits relatively abundant molecular ions compared with the "Inert" ion source, while the "High efficiency source" (HES) provides mass spectra with depleted molecular ions compared with the "Inert" ion source or NIST library mass spectra. These conclusions are demonstrated and supported by experimental data in nine figures and two tables.