Metabolic Fingerprinting of Biofluids by Infrared Spectroscopy: Modeling and Optimization of Flow Rates for Laminar Fluid Diffusion Interface Sample Preconditioning

Abstract

The laminar fluid diffusion interface (LFDI) is a microfluidic tool that manipulates the composition of liquid mixtures by exploiting differences among diffusion coefficients of the dissolved components. One application is the preprocessing of (bio)fluids prior to spectroscopic characterization. For example, in the case of infrared (IR) spectroscopy, the technique can improve sensitivity to low-concentration serum metabolites. The practical benefit is “metabolic fingerprinting” measurements that are more sensitive to low-concentration metabolites than are the counterpart measurements for the original serum sample. Optimal use of the LFDI technique has proven elusive, since the composition of the product of interest is very sensitive to the choice of flow rates for the liquid streams entering and emerging from the LFDI channel. To provide the basis for optimal use, this study had the objective of developing a simulation package that predicts the composition of the LFDI product, given the LFDI structural and operating parameters. To demonstrate the utility of the simulations, composition of the LFDI products predicted for two illustrative sets of trials were compared with experimental data. The flow rates thus derived provided a LFDI product that is relatively rich in serum metabolites, while largely depleted of protein, and very well suited for subsequent IR spectroscopic characterization.

Infrared Spectroscopy of Blood

“…Consequently, the method assisted the sequestering and quantifying of serum creatinine in a range of 0.7-16 mg/dL from high concentrated molecules like protein. 33,287,288 Another strategy was employed to determine and quantify the lipidomic profile by eliminating the proteins in the serum and pre-concentrating only the non-polar analytes using solvent extraction. The study has demonstrated an improvement in the predictions of levels of cholesterol and triglycerides compared to direct ATR analysis on serum.…”

Metabolomics as a Challenging Approach for Medicinal Chemistry and Personalized Medicine

“…50,100 Some other techniques, such as electrochemical array detection, Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy, have also become increasingly used for metabolomics. 101,102 The choice of analytical platform may remain greatly dependent on the biological questions and the samples that require analysis (in terms of both nature and number). Many existing platforms combine both NMR and MS, which are described as complementary and synergetic tools.…”

The emergence of metabolomics as a key discipline in the drug discovery process

“…The resultant infrared absorbance spectrum is characteristic of the functional groups within the sample and thus constitutes an unique fingerprint [39]. This is a promising analytical tool for metabolomic studies however, it is important to note that the presence of water in a sample may influence the bands at certain specific wave number and that environmental conditions around the FT--IR instrument can cause variations in the spectra.…”