Magnetic Resonance Microimaging and Numerical Simulations of Velocity Fields Inside Enlarged Flow Cells Used for Coupled NMR Microseparations

Abstract

The coupling of various chemical microseparation methods with small-scale NMR detection is a growing area in analytical chemistry. The formation of enlarged flow cells within the active volume of the NMR detector can significantly increase the coil filling factor and hence the signal-to-noise ratio of the NMR spectra. However, flow cells can also lead to deterioration of the separation efficiency due to the development of complex flow patterns, the form of which depend on the particular geometry of the flow cell and the flow rate used. In this study, we investigated the flow characteristics in different flow cell geometries relevant to the coupling of capillary liquid chromatography and NMR. Computational fluid dynamics was used to simulate fluid flow inside flow cells with a volume of ~ 1 µL. Magnetic resonance microimaging was used to measure experimentally the velocity fields inside these flow cells. The results showed good agreement between experiment and simulation and demonstrated that a relatively gradual expansion and contraction is necessary to avoid areas of weak recirculation and strong radial velocities, both of which can potentially compromise separation efficiency.An essential component in the purification and analysis of unknown compounds is efficient separation of individual components from an often complex chemical or biological system. Advances in microseparations, include techniques such as capillary liquid chromatography (cLC), 1 capillary electrophoresis (CE), 2 and capillary electrochromatography 3 have played a large role in improving the separation efficiency. The chromatographic dilution (D) of cLC, for example, is given by (1) where C 0 is the initial concentration of the analyte, C max is the final compound concentration at the peak maximum, r is the column radius, ϵ is the column porosity, k is the retention factor, L is the column length, H is the column plate height, and V inj is the injected sample volume. Equation 1 shows that a smaller column radius results in less chromatographic dilution and higher concentration elution peaks. The smaller scale is also much more amenable to very rapid separations. In addition to these general benefits of microseparations, in electrophoretic separations the high surface area-to-volume ratio of the small capillaries used in CE systems,

Nuclear magnetic resonance in microfluidic environments using inductively coupled radiofrequency resonators

“…As will be shown in the following, the sensitivity is comparable to that reported by Zhang and Webb in a recent study of flow profiles in capillaries of similar dimensions [33].…”

“…NMR spectra from lipid globules with a voxel volume as small as 5 pL have been obtained in this manner [26], and experimental techniques integrating liquid chromatography and capillary electrophoresis with NMR have been developed [27][28][29][30][31][32]. Recently, Zhang and Webb obtained detailed flow velocity field information in sub-mm size capillaries [33]. While these studies have all relied on resistive coupling of the microcoils, it is the goal of the present paper to show that inductive, wireless coupling offers similar performance.…”

“…The water inside the coil gives a signal that is more than two orders of magnitude stronger than outside, due to the combined effect of the higher rf amplitude inside the solenoid and the enhanced sensitivity. In the remainder of this paper, this effect is treated quantitatively as a function of the cross-inductance and quality factor of the resonator, and it is shown that the Hagen-Poiseuille flow profile inside a capillary of 200 lm inner diameter can be measured using this principle with a sensitivity that is comparable to similar measurements carried out with directly connected microcoils [33].…”

Microfluidic gas-flow profiling using remote-detection NMR

“…Thus, the volume that gets exchanged only slowly, which is responsible for the stationary branch of the fork, is Ϸ300 nl. The observation of this forking emphasizes the complementary character of direct f low imaging (22)(23)(24)(25) and TOF f low imaging. The former provides a map of local velocity vectors, whereas the latter is able to distinguish between different f low paths and shows how well a certain volume element is connected to the f low field.…”

Nuclear magnetic resonance coupled microseparations

“…In practice, however, such a geometry can result in complex fluid flow patterns 26 -28 which degrade the efficiency of the separation. Figure 3 shows simulated flows in two different flow cells, 29 one with an abrupt transition from inlet capillary to detection cell and the other with a more gradual one. The normalized transition length is defined as the transition length divided by the diameter of the inlet capillary.…”