Mass Spectrometry Applications in Clinical Diagnostics

Abstract

Mass Spectrometry (MS) is an analytical technique used for determining the elemental composition of samples, quantifying the mass of particles and molecules, and elucidating the chemical structure of molecules. Various types of MS with high specificity, such as Liquid Chromatography (LC-MS), Gas Chromatography (GC-MS), and Matrix-Assisted Laser Desorption/Ionization/Time-Of-Flight (MALDI-TOF MS), are being increasingly valued and utilized as tools in clinical laboratories [1]. These MS techniques overcome the limitations of immunoassays and offer many advantages over earlier approaches.Clinical laboratories use the MS technology for disease screening, diagnosis of disease and metabolic disorders, monitoring of drug therapy, identifying drug toxicity and poisoning, and discovering new biomarkers. Therapeutic monitoring of immunosuppressant drugs using MS is well established. Limitations of immunoassays such as nonspecific binding of the antibody and cross-reactivity with metabolites that often result in overestimation have made the more accurate LC/MS/MS methodologies the assays of choice [2]. LC/ MS/MS has become the standard for assay of steroid hormones for diagnosis of endocrine disorders. Vitamin D analysis by LC/MS/MS is widely used in the clinical laboratory today. Whereas immunoassays are unable to distinguish between 25-hydroxy vitamins D2 and D3, the LC/MS methodologies are able to measure these levels separately so the contribution of each to the total can be determined.The capability of measuring thyroid hormones by tandem MS was developed recently and this has overcome the issues associated with immunoassays [3]. Triple quadrupole MS/MS is the preferred methodology for toxicology screening and for toxic drug quantitation [4]. In newborn and prenatal screening programs, electrospray tandem MS has made possible identification of inborn errors in metabolism or genetic defects so that preventive and medical intervention can be implemented promptly to relieve or treat the disease [5]. One of the new ways that MS technology is being used is in proteomics, for quantitative identification of small amounts of proteins or molecules in blood to serve as biomarkers. This has opened up the discovery of new tumor markers as a potentially promising area of application of MS [6]. The intensive research into metabolomics, the assessment of endogenous metabolites as new disease biomarkers, is another promising applications of MS, which has been demonstrated to be very well suited to discovery and clinical application of metabolite profiles [7]. Another area of increasing interest is the use of automated MALDI-TOF MS for rapid identification of microorganisms in clinical microbiology laboratories [8].Yet, there are still challenges in the clinical application of this technology, including sample preparation, online extraction, throughput, automation, laboratory information system interfacing, inter-instruments standardization and harmonization, and FDA regulation. With emerging technologies in MS, we expect to see more...

Principal Component Analysis with Linear and Quadratic Discriminant Analysis for Identification of Cancer Samples Based on Mass Spectrometry

“…The control population was composed of men with no previous history of prostate cancer and serum PSA < 1 ng mL -1 . The prostate cancer samples were acquired from patients with serum PSA ≥ 4 ng mL -1 , digital rectal exam (DRE) evidence and single sextant biopsy evidence of prostate cancer (Gleason scores [4][5][6][7][8][9]. More details about the sample acquisition can be found in Petricoin III et al 16 …”

“…2,3 This technique has been increasingly utilized in biomedical and clinical research, 4 since it can overcome many limitations of classical immunoassays 5,6 and supports the development of fast and less-invasive clinical procedures. [7][8][9] MS is usually coupled with chromatography such as liquid chromatography (LC-MS) and gas chromatography (GC-MS).…”

“…Other techniques such as surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) are often used in MS applications, including disease screening and diagnosis. 5 Some examples of MS applications includes toxicology screening and toxic drug quantification using quadrupole MS/MS; 10 identification of inborn errors in metabolism or genetic defects in newborns for prenatal screening programs using electrospray tandem MS; 11 detection of drug-induced hepatotoxicity using MS-based metabolomics; 12 and identification and quantification of bleomycin in serum and tumor tissue by high resolution LC-MS. 13 MS-based techniques have been largely employed for cancer identification, such as for breast cancer, 14 prostate cancer, 15,16 ovarian cancer, 17 lung cancer, 18 and pancreatic cancer; 19 as well as for identifying many biomarkers. 18,[20][21][22][23][24] One of the main fields using MS data is metabolomics, which aims to identify and quantify small molecules involved in metabolic reactions.…”

Proteomics in Diagnosis: Past, Present and Future

“…As discussed being a cumbersome and time consuming technique 2DE could not reach the clinics, however, Mass spectrometry, especially MALDI-TOF have successfully made its way to pathology labs in the present decade. Several diseases like cancer, Alzheimer's disease, Amyloid lateral sclerosis, renal amyloidosis, and Severe combined immunodeficiency can now be diagnosed using mass spectrometry and its variants [28][29][30][31][32][33][34].…”

Clinical proteomics: Promises, challenges and limitations of affinity arrays

“…Technical complexity of the analysis process, a still limited throughput and lacking sensitivity are aspects that have been restrictive to date. Sample preparation is still complex, and the capacity for quantitative measurements is not yet at a level required by routine diagnostics in a clinical setting [6,7]. Another obstacle is the fact that proteins do not act on their own usually, but exhibit their activity together with other proteins or ligands.…”