Mass Spectrometry Resources
Mass Spectrometry is used to determine molecular weight, provide structural information on compounds, monitor reaction progress, determine sample purity, and quantify sample concentration and can be used to gain structural information. Analysis can be performed using sample volumes of less than 1 uL and concentrations of <1 uM. This typically corresponds to 10-15 grams of material. Using low resolution mass spectrometry, groups can quickly gauge reaction progress. The figure below shows a reaction sequence developed in the Thomson lab.
In this case, 0.5 Da accuracy is more than sufficient to monitor reaction progress using mass spectrometry. By improving the accuracy wand resolution of the mass spectrometer, users can take advantage of the difference between the nominal mass of a compound and the theoretical monoisotopic mass. For instance, the monoisotopic mass of CO is 27.994 Da vs. N2 is 28.006, thus uniquely distinguishing the two compounds from one another. Modern mass spectrometers are capable of measuring this difference and so many journals and reviewers frequently require accurate mass analysis with agreement between the measured mass and theoretical mass to be better than 0.5 ppm (0.0025 Da for a 500 Da compound). The spectrum at right shows an example from the Silverman group of a possible treatment for neurodegenerative diseases analyzed on the Agilent 6210 LC-TOF mass spectrometer. The synthesis of these novel compounds based on rational models has lead to many successful treatments, including the development of pregabalin, better known by the trade name Lyrica™, for the treatment of fibromyalga.
Due to the complexity of instrumentation required to perform accurate mass analysis and the incredible diversity of compounds synthesized at NU on a regular basis, IMSERC maintains a suite of instruments to meet NU research needs. IMSERC provides walk-up access to an instruments with <0.5 Da accuracy for nearly any molecular compound 24 hrs / day and 7 days / week and also provides staff run accurate mass analysis for all compounds with a less than two day turnaround time. IMSERC provides access to multiple ionization techniques for both walk-up and staff-supported analysis to ensure that the proper instrument is readily available to analyze nearly every sample.
The IMSERC provides three classes of ionization techniques. Atmospheric pressure ionization (API) includes electrospray (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photo ionization (APPI) and is primarily used for analysis of polar molecules and biological materials, such as proteins and oligosacharides. Electron Impact (EI) and chemical ionization (CI) are primarily used for small (<1000 Da) non-polar compounds that do not ionize using API. Matrix Assisted Laser Ionization (MALDI) is primarily utilized for higher molecular weight compounds with vapor pressures that are too low for EI/CI, and do not ionize well using API techniques. MALDI uses a small molecule matrix to assist in the ionization process of larger molecules. There are many varieties of matrix available for use with different compounds. In addition, IMSERC provides four introduction techniques. Direct injection probe (DIP) can be used with neat samples that are volatile when heated. Gas Chromatography (GC) introduction is used to separate volatile compounds before analysis and provides a user friendly introduction method fo EI analysis. Liquid Chromatography (LC) can be performed on samples with higher molecular weight or polarity and is typically combined with API techniques. MALDI is typically used for proteins, polymers and other samples that have poor volatility, but cannot be ionized using API. This group of instruments allows users to analyze 80-90% of synthesized compounds using walk-up instrumentation with the remainder needing staff-run instruments.
Special Projects in Mass Spectrometry
Sometimes the needs of your research exceed the capabilities of our walk-up instrumentation. Perhaps you need a different type of ionization or you need separation methods developed for your synthetic product. For usage outside of the normal bounds of our walk-up instruments and submission process, please consult the IMSERC staff. We are happy to meet with you to discuss the needs of your project, the capabilities you require, the data you have already generated, and how to best achieve your research goals. We will work with you to develop your project and train you in the necessary advanced operations of the instrumentation. If we do not have the instrumentation you require here on site, we will seek out the resources through our connections through Argonne National Labs, the Chicago Biomedical Consortium and beyond. Our goal is to provide you with one location where you can come for all your mass spectrometry research concerns. Please do not hesitate to contact IMSERC staff for project and methods development.