Eight Emerging Applications of Mass Spectrometry
The history of mass spectrometry (MS) dates back to 1918, with the discovery by J.J. Thompson for identification of new isotopes of common elements like chlorine. The potential of mass spectrometry was immediately realized by the Governments and used in war efforts for the development of early nuclear weapons. Slowly, mass spectrometers transitioned to Chemical, Petroleum industries and Biotech companies. The revolutionary use of MS began by the introduction of microelectronics and advances in material science, where the instrument became user-friendly and easy to use. Finally, the stand-alone MS instruments for analyte identification and confirmation, transformed to computer interfaced modern mass spectrometers coupled to an analytical front end. These new forms are complete analytical systems to solve complex scientific problems.
Mass spectrometry works by ionization and determination of the masses of charged analyte molecules. The introduction of tandem mass spectrometry has led to rapid expansion into new fields of science. This article highlights some of the wide range of applications which can be achieved using mass spectrometry.
1. Metabolomic snapshots
Metabolomics is the analysis of all the small molecule metabolites in a biological system. This can be very challenging to analyze, given the complexity of the system and internal and external interferences. But, MS coupled to liquid chromatography (LC-MS) based metabolomics applications remarkably changed its use in drug discovery and development.
An example worth mentioning here, is using high content LC-MS/MS assays to study the peptidoglycan pathway response in bacteria and for understanding antibiotic resistance [1,2]. By these studies, new drug targets can be identified with the chance of least possible resistance. Further, metabolomics studies can provide individualized patient care to treat the bacterial infections without the risk of developing antibiotic resistance.
2. Biomarker discovery
Pushing the limits of detection and quantification in LC-MS specialized its use to biomarker research. Comparative analysis between a healthy person and patient biological specimens using MS can easily identify the significant differences between the two samples in terms of metabolites or proteins or lipids. Sometimes, quantification of biomarkers in ng- fmol range can be achieved by mass spectrometry, not possible with the conventional methods.
A good example here will be profiling analysis in cancer patients. Many papers have been published using this technique for discovering unique identifiers of the disease [3,4]. A recent study [5]showed quantification of circulating tumor DNA as a diagnostic marker using mass spectrometry for 1) identification and differentiation of liver diseases 2) determination of treatment response.
3. Biologics front-screening
A transition from conventional ligand based assays to mass spectrometry based assays has added practical value in biotech industries. The number of protein drugs and monoclonal antibodies has increased over the past few years, but, there are no rapid quantification methods which can differentiate the isoforms of proteins or to determine if the protein is active or folded, etc. The power of mass spectrometry to overcome these disadvantages of ligand based assays has taken center stage and is currently being explored for biologics quantification.
Given the specificity of MS/MS assays, this approach is currently being used complimentary to the conventional methods. Currently, MS methods are being used to study different post translational modifications on proteins in different diseases. This helps with patient stratification and cost-effective rapid clinical sample analysis.
4. Genomics and epigenetic applications
Cancer is a well- known disease characterized by mutations in the functional genes. Recent studies have shown the importance of epigenetics in causing cancer and other related diseases [6]. These epigenetic changes can be easily quantified using mass spectrometry. Chromatographic separations were a challenge before and now, with recent advances in HPLC and mass spec techniques, this approach has been made possible.
For example, in acute myeloid leukemia, genetic mutations and epigenetic TET effects play an important role in controlling the disease condition [7]. In this study, LC-MS technique can be used to explore the underlying biology, study the treatment response and identify the new drug targets.
5. Forensic lab
Did you know that the detector sensors we find at the airports are nothing but compact mass spectrometry instruments? They are used as homeland security checks for identification of illegal drugs, explosive compounds, exotics or to confirm substance drug abuse. Steroid overuse especially by athletes and celebrities can be easily measured using MS. In Forensic studies, MS really comes in handy to identify the barely detectable traces left by the suspect. In toxicology studies, MS is used to detect potential toxins by analyzing the blood samples. This will help determine the poison dose in the blood of victims and identify the time and death of the person [8].
A more recent scientific progress is analyzing the nicotine levels (smoking) or chemical pollutants in human lungs just by a simple inhaler MS system.
6. Newborn screening
With advances in science over the past 25 years, we are able to screen newborns for the risk of diseases like cardiovascular disease or diabetes etc. by using MS/MS [9]. This approach gives less false positives compared to the conventional newborn screening methods and includes testing of different biological specimens. For example, lysosomal storage disorders are asymptomatic during childhood, but progress with symptoms to advanced stages. MS has the capacity to identify these types of risks during childbirth using biomarkers or metabolomics based studies.
7. Geology and Space science
Another exciting application of mass spectrometry is Astronomy and Environmental Sciences. MS can determine the elements and isotopes in solar wind, record climate changes or geographically locate oil deposits by analyzing the petroleum precursors in rock. Therefore, MS instruments are widely used by NASA to explore the universe. E.g. Saturn’s atmosphere is analyzed for its air composition and quality to estimate the percentage of chemicals and toxins on that planet.
8. The taste of food
MS is being used in the food industry for pesticide testing, allergens, etc. and to check the quality of food before being released into the market. This application dominates the use of MS in supply chains and product safety departments.
For example, honey, a daily ingredient is constantly adulterated with sulfonilamides which can lead to antibiotic resistance in the consumer with time. By using MS, quick and rapid assays to determine the content of sulfanilamides in honey can be tested.
The famous chipotle scandal and horse meat scandal are a few examples where MS testing was done to detect the microbes and specific protein biomarkers to check the quality of meat used in their food products.
Imagination and creativity are the limit
There are many misconceptions about mass spectrometry and its usage – Often, it is imagined as a huge instrument and sample analysis using this technique is very complex and challenging. In reality, MS instruments are very compact, accurate, easy-to-use, flexible and rapid. The data analysis is performed by user-friendly automated software and can be used even for discoveries.
The use of mass spectrometry as forensic detectors, newborn screening tools, breath analyzers, and an antibiotic resistance profiling technique, are a few applications, and there are many more with the recent new advances in technology. We may not be always be aware of this, but, mass spectrometry is used in our daily life on a regular basis.
Biography
Harika Vemula, PhD in Analytical Chemistry with strong background in analytical method development, chromatographic separations, MS/MS, metabolomics and antibodies. She is currently working as a Senior Scientist for Merck MSD, Missouri, USA in Analytical R&D. She is a member of American Association of Pharmaceutical Scientists, American Society of Mass Spectrometry (ASMS), Sigma Xi Research Society – Kansas City Chapter and member of Mid-west Mass spectrometry group
References
1. Vemula H, Ayon NJ, Gutheil WG (2016) Cytoplasmic peptidoglycan intermediate levels in Staphylococcus aureus. Biochimie 121: 72-78.
2. Vemula H, Bobba S, Putty S, Barbara JE, Gutheil WG (2014) Ion-pairing liquid chromatography-tandem mass spectrometry-based quantification of uridine diphosphate-linked intermediates in the Staphylococcus aureus cell wall biosynthesis pathway. Anal Biochem 465: 12-19.
3. Yuan J (2016) Circulating protein and antibody biomarker for personalized cancer immunotherapy. J Immunother Cancer 4: 46.
4. Huang W, Qi CB, Lv SW, Xie M, Feng YQ, et al. (2016) Determination of DNA and RNA Methylation in Circulating Tumor Cells by Mass Spectrometry. Anal Chem 88: 1378-1384.
5. Lin CL, Kao JH (2016) New perspectives of biomarkers for the management of chronic hepatitis B. Clin Mol Hepatol 22: 423-431.
6. Hamidi T, Singh AK, Chen T (2015) Genetic alterations of DNA methylation machinery in human diseases. Epigenomics 7: 247-265.
7. Jaiswal M, Bhar S, Vemula H, Prakash S, Ponnaluri VK, et al. (2017) Convenient expression, purification and quantitative liquid chromatography-tandem mass spectrometry-based analysis of TET2 5-methylcytosine demethylase. Protein Expr Purif 132: 143-151.
8. Ojanpera I, Kolmonen M, Pelander A (2012) Current use of high-resolution mass spectrometry in drug screening relevant to clinical and forensic toxicology and doping control. Anal Bioanal Chem 403: 1203-1220.
9. Ombrone D, Giocaliere E, Forni G, Malvagia S, la Marca G (2016) Expanded newborn screening by mass spectrometry: New tests, future perspectives. Mass Spectrom Rev 35: 71-84.
