Miniaturization in the Future of Mass Spectrometry · 2016-03-04 · for Mass Spectrometry 2006, 17...
Transcript of Miniaturization in the Future of Mass Spectrometry · 2016-03-04 · for Mass Spectrometry 2006, 17...
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Advion expression
Compact Single Quadrupole API
Mass Spectrometer
Lecture 7, Page 34
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Cart-Based LC/MS: Move where you want it and plug it in.
Lecture 7, Page 35
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Specifications
• Ion Source: ESI with APCI option (swapped with minimal effort)
• ASAP: Atmospheric Sample Analysis Probe employs APCI
• API: orthogonal ion sampling from heated capillary – allows small single turbo pump (Patents filed**)
• Analyzer: Quadrupole Mass filter
• Detector: Electron multiplier with dynode
• Flow rate range:10 µL/min to 1 mL/min
• Polarity: +ve and –ve ion in sequential analyses
• Mass Range: 10 – 2,000 amu (possible extension to 1,500)
• Scan Speed: 10,000 amu/sec (compatible with UPLC)
• Resolution: 0.5-0.7 Da (FWHM) at 1000 amu/sec over entire mass range
• Sensitivity: 25 ng reserpine injected on column, measured at 10:1 S/N with full scan 100 to 1000 amu (achieved 20 - 200 pg)
• Mass accuracy: 0.1 Da over entire mass range
• Mass stability: 0.1 Da over 30 day
Lecture 7, Page 36
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Mass Resolution
10 pmol/uL infusion of Quaternary Amine Mix (major peaks are (M+H)+ ions)
Tetramethylammonium, 74.10 Tetrabutylammonium, 242.28 Tetradecylammonium, 578.55
Tetraoctadecylammonium, 1027.16
Lecture 7, Page 37
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• Little or no sample preparation • No chromatography • Data in < 1 minute The closed end of a glass capillary is dipped into the sample of interest or scraped on a solid surface, and then placed into the CMS for analysis. Ideal for: • Reaction monitoring • Compound ID • Food safety • Natural products
ASAP® – Atmospheric Solids Analysis Probe
Lecture 7, Page 38
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SPME Sample Preparation for Drugs in Urine
The Procedure
Lecture 7, Page 39
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Oxycodone C18H21NO4 MW: 315.36
Codeine C18H21NO3 MW: 299.36
Morphine C17H19NO3 MW: 285.34
SPME sample procedure for three opiates in urine with (Fiber was LC tip C18) 1. SPME Tip was conditioned in MeOH for 5 minutes 2. Equilibrium in water was 10 minutes 3. Extraction time: 10 minutes (Immersed tip in sample where the sample was stirred by magnet stir
bar. 4. After extraction, the SPME fiber/sample was dried in air for 2 minutes 5. ASAP-SPME-MS analysis
Preparation of fortified urine sample Each compound was a stock solution at 1 mg/ml in methanol. A 50ul stock solution of each compound was spiked in 1.85 ml urine which made a fortified urine sample with 25 ng/ul of the three opiates.
Three Opiates: Sample preparation and SPME Extraction
Lecture 7, Page 40
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Mass spectra of three opiates
ASAP-SPME-MS Analysis of Opiates in Urine (Codeine, Morphine and Oxycodone: 25ng/ul in Urine)
Total Ion Current
XIC for m/z 286,
Morphine [M+H]+
Oxycodone [M+H]+
Codeine [M+H]+ Morphine
[M+H-H2O]+
Lecture 7, Page 41
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Extraction procedure for three opiates in urine with SPME (LC tip C18) 1. SPME Tip was conditioned in MeOH for 10 minutes 2. Equilibrium in water for 5 minutes 3. Extraction time: 5 and 15 minutes (Immersed tip in sample where the sample was stirred by
magnet stir bar. 4. After extraction, the SPME fiber was dried in air about 2 minutes 5. ASAP-SPME-MS analysis
Preparation of fortified urine sample The stock solution of testosterone was 1.0 mg/ml in methanol . A 25 ul of stock solution for of testosterone was spiked in 4.75 ml urine which made a fortified urine sample with 5 ng/ul of testosterone.
Testosterone: Sample preparation and SPME Extraction
Testosterone C19H28O2
MW: 288.2
Lecture 7, Page 42
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ASAP-SPME-MS Analysis of 5ng/ul testosterone in urine Extract time: 15 mins
used tip after cutting off the black part
Mass spectrum of testosterone in urine
Extract ion current of the m/z 289
Total ion current
[M+H]+
Lecture 7, Page 43
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Amlodipine in Urine
Amlodipine C20H25ClN2O5
MW: 408.87
Preparation of fortified urine sample The stock solution of amlodipine was 1.0 mg/ml in methanol by dissolving a 2.5 mg tablet in 2.5 mL Methanol. The 50ng/ul and 100ng/ul amlodipine in urine was made by spiking the stock solution in urine sample.
All the SPME fiber for amlodipine test was used without conditioning in solvent
Lecture 7, Page 44
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ASAP-SPME-MS Analysis of 50 ng/ul Amlodipine in urine Extract time: 5 mins, SPME LC Tips SCX/C18
Mass spectrum of Amlodipine in urine
XIC for m/z 406
Total ion current
[M+H]+
C20H25ClN2O5
MW: 408.87
Lecture 7, Page 45
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ASAP-SPME-MS of 50ng/ul Amlodipine in urine Extract time: 5 mins, SPME LC Tips C18
Lecture 7, Page 46
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Jack Henion, Nigel Sousou, Advion, Inc.
and
Brian Musselman, IonSense, Inc.
Rapid Screening of ‘White Powders’ for Organic Compounds Using a DART-Equipped API Compact
and Transportable Mass Spectrometer.
Lecture 7, Page 47
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Mass Spectrometry Experimental
• Expression Compact Mass Spectrometer (CMS) – Single quadrupole: mass range 10-1200 m/z units
• Full-scan or SIM – Does not provide EI, MS/MS or HRMS – Does provide molecular weight
– API inlet amenable to ESI, APCI, DART, etc. • Can do infusion, FIA, LC/MS, IC/MS, SFC/MS, TLC/MS
– Mass Spec fits in a hood or on a cart and is – transportable – Pos/Neg DART modes can be used – Sample introduction via porous swab
• Swab with sample is robotically introduced to ionization region
Lecture 7, Page 48
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‘Meth-Labs’ Continue to be Found
• State police charge man, woman after discovering meth lab near Syracuse, NY
Lecture 7, Page 49
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Methamphetamine in Baking Powder DART CMS
Methamphetamine Standard
2% Methamphamphetamine in Baking Powder
MW = 149
(M+H)+
Lecture 7, Page 50
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Summary of Staged Meth Lab Scene ( Imagine this Situation)
• A Meth Lab is in the forrest a half-mile off the road next to an airstrip
• An airplane lands to pick up several kilos of fresh-made Meth as a white powder
– Aircraft are often used to quickly transport illegal drugs
• While quickly loading a box of Meth plastic bags into the airplane a plastic bag of Meth poweder is dropped on the ground
• The police have received a tip and rush to the scene
• The airplane quickly takes off as the police arrive
• The dropped bag of Meth is analyzed on-site by a transportable DART-compact MS system. – An example situation which demonstrates that simple, inexpensive mass spectrometry
can be taken to the sample rather than the sample taken to the lab!
• Let’s watch a video of this ‘pretend’ situation but with real on-site DART-CMS analysis of methamphetamine in a white powder.
Lecture 7, Page 51
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Meth-Lab Drug Bust (Simulated) Video
Lecture 7, Page 52
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Summary MS Miniaturization
• Transportability within the laboratory is possible
• Many applications do not require superlative performance
• Personal access to MS is desired but current costs are too high for personal systems
• Laboratory space is limited so smaller is better
• Ease-of-use MS would help be well received
• Low cost systems could be more prevalent
Lecture 7, Page 53
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References
• Sassi, A. P.; Hooper, H. H., Making analysis in the life sciences faster through miniaturization. Am. Lab. 2000, 32 (October), 36-41.
• Gac, S. L.; Berg, A. v. d., Miniaturization and Mass Spectrometry. RSC Publishing: Cambridge CB4 0WF, UK, 2009; p 315.
• Chaudhary, A.; van Amerom, F. H. W.; Short, R. T.; Bhansali, S., Fabrication and testing of a miniature cylindrical ion trap mass spectrometer constructed from low temperature co-fired ceramics. International Journal of Mass Spectrometry 2006, 251 (1), 32-39.
• Lammert, S. A.; Rockwood, A. A.; Wang, M.; Lee, M. L.; Lee, E. D.; Tolley, S. E.; Oliphant, J. R.; Jones, J. L.; Waite, R. W., Miniature Toroidal Radio Frequency Ion Trap Mass Analyzer. Journal of the American Society for Mass Spectrometry 2006, 17 (7), 916-922.
• Janfelt, C.; Graesboll, R.; Lauritsen, F. R., Characterization and optimization of membrane inlets for a miniature ion trap mass spectrometer operating at a high background pressure of humid air. International Journal of Mass Spectrometry 2008, 276 (1), 17-23.
• Malcolm, A.; Wright, S.; Syms, R. R. A.; Dash, N.; Schwab, M.-A.; Finlay, A., Miniature Mass Spectrometer Systems Based on a Microengineered Quadrupole Filter. Analytical Chemistry 2010.
• Malcolm, A.; Wright, S.; Syms, R. R.; Moseley, R. W.; O'Prey, S.; Dash, N.; Pegus, A.; Crichton, E.; Hong, G.; Holmes, A. S.; Finlay, A.; Edwards, P.; Hamilton, S. E.; Welch, C. J., A miniature mass spectrometer for liquid chromatography applications. Rapid Commun Mass Spectrom 2011, 25 (21), 3281-8.
• Tadjimukhamedov, F. K.; Jackson, A. U.; Nazarov, E. G.; Ouyang, Z.; Cooks, R. G., Evaluation of a Differential Mobility Spectrometer/Miniature Mass Spectrometer System. Journal of the American Society for Mass Spectrometry 2010, 21 (9), 1477-1481.
Lecture 7, Page 54