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

Abstract

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 β‐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.

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

“…Figure 5 shows the analysis of saliva that was obtained from a recreational cannabis smoker 1, 30, and 60 min after smoking a quarter of a cannabis cigarette. As shown, the saliva analysis is somewhat similar to whole blood analysis 18 . It shows palmitic acid at ~3.8 min and linoleic, oleic, and stearic acids after 4 min, plus cholesterol at about 5.9 min which is the biggest peak in saliva.…”

“…GC-MS with Cold EI is reviewed in previous studies [14][15][16] and further described in previous studies. 18,[28][29][30][31] In Cold EI, the GC column flow output is mixed with helium make-up gas ($50-60 mL/min total column and make-up flow rate), in front of a supersonic nozzle at the end of a temperature-controlled transfer line.…”

“…The GC–MS with Cold EI system that was used is based on the combination of an Agilent 7890A GC + 5977 MSD (Agilent Technologies, Santa Clara, CA, USA) with the Aviv Analytical Cold EI (Aviv Analytical LTD, Hod Hasharon, Israel). GC–MS with Cold EI is reviewed in previous studies 14–16 and further described in previous studies 18,28–31 . In Cold EI, the GC column flow output is mixed with helium make‐up gas (~50–60 mL/min total column and make‐up flow rate), in front of a supersonic nozzle at the end of a temperature‐controlled transfer line.…”

“…We used for saliva analysis GC–MS with Cold EI with its 15 m 0.32 mm ID column (0.1 μ DB1HT film) with 8 mL/min column flow rate that was programmed at its end into 32 mL/min. This way saliva was analyzed similarly to whole blood 18 and indeed its components correlated with those of whole blood. In order to speed up the analysis from 10 min into sub 1 min (real‐time), we used our Open Probe Fast GC–MS as described in Amirav et al 23,24 Open Probe Fast GC–MS is based on the combination of Open Probe inlet, 26 a low thermal mass ultra‐fast GC, 27 in‐vacuum EI ion source and a MS of GC–MS for obtaining real‐time analysis with separation 23,24 .…”

“…This study also describes a new type of a “SalivaProbe” device for sampling saliva from human tongues and its introduction “as is” to GC–MS with Cold EI. The SalivaProbe is similar to our BloodProbe, 18 and it is based on a modified ChromatoProbe for the sampling of saliva as described below. The ChromatoProbe was developed by Amirav and Dagan 19 as the direct sample introduction (DSI) device.…”