Magnetic Resonance Diagnostics: A New Technology for High-Throughput Clinical Diagnostics

Abstract

Magnetic resonance diagnostics (MRD) uses automated, high-throughput nuclear magnetic resonance (NMR) spectroscopy for the rapid identification and quantification of small-molecule metabolites in biofluid mixtures (blood, urine, saliva, cerebrospinal fluid, and others). Specifically, MRD involves using a high-field (400 MHz) NMR instrument equipped with a small-volume flow probe and robotic sample handler to rapidly load biofluid samples and to collect their 1H NMR spectra. Spectral deconvolution software automatically assigns individual peaks to particular compounds and calculates concentrations from peak areas. MRD uses the principle of chemical shift separation to physically separate and identify individual compounds directly from 1H NMR spectra, thus avoiding chromatographic separation steps (e.g., HPLC, gas chromatography, and capillary electrophoresis). MRD is useful for rapid (<2 min per sample) qualitative and quantitative assessment of small-molecule metabolites. NMR spectroscopy is not new to the field of clinical chemistry. Indeed several important applications have already been demonstrated in the area of diagnosis and therapeutic monitoring of metabolic disorders (1)(2)(3)(4), in toxicologic and renal testing (5)(6), and in the profiling of blood lipoproteins and cholesterol (7). An emerging approach to enable high-throughput in vivo toxicology is called metabonomics, which uses high-resolution NMR to rapidly evaluate the metabolic status of an animal (8)(9). A key limitation to all of these NMR approaches is that they depend on manual sample handling and/or manual (i.e., expert) spectral analysis. This has made most NMR approaches to clinical analyses far too slow or too costly for routine chemical profiling or high-throughput screening. Because MRD is fully automated (sample handling, spectral collection, and spectral analysis are all handled by robots or computers), this technique offers the potential for high-throughput, comprehensive, and inexpensive chemical analysis of a wide range of biofluid samples. To demonstrate the potential …