High Resolution Nuclear Magnetic Resonance Spectroscopy for Lab-on-a-Chip Devices via Inductive Coupling

Ryan, Herbert, Mechanical and Aerospace Engineering - School of Engineering and Applied Science, University of Virginia
Utz, Marcel, Department of Mechanical and Aerospace Engineering, University of Virginia

The goal of this work is to create a integrated microcoil "lab-on-a-chip" (LOC) device for inductively coupled Nuclear Magnetic Resonance spectroscopy, with sufficient sensitivity and spectral resolution such that metabolomic analysis, for small sample volumes in a wide range of applications, becomes feasible.

Much excitement has surrounded the field of microfluidic LOC devices for reasons of cost and high-throughput capability. These devices combine reagents in a miniaturized chemical reactor network to sort, process, and ultimately analyze a desired sample. Fabrication in glass or polymer substrates via lithographic methods, similar to those used in microelectronics, make LOC devices very cheap and expendable. In contrast to this emerging field is Nuclear Magnetic Resonance (NMR) spectroscopy which is an established tool, ranging in applicability from protein structure determination to non-invasive whole body imaging (called Magnetic Resonance Imaging (MRI) in practice). Although in principle, NMR possesses the high specificity needed for a microfluidic analytical tool, in practice there are several limitations relating to sensitivity and resolution. This thesis reports on methods to integrate NMR spectroscopy with microfluidic devices without sacrificing sensitivity.

Theoretical aspects of NMR are explored in regards to applicability of this method to the small sample regime. Further, microcoil fabrication and integration work is presented for inductively coupled coils. Planar spiral resonators are fabricated lithographically by etching Cu, laminated on polyimide. Coil performance is characterized by both magnetic resonance images and spectroscopy. A single-scan limit of detection LODt = 0.95 nmol s^1/2 was obtained from sample volumes around 1 microlitre.

The sensitivity of this approach is compared with contemporary methods that utilize solenoid, micro-stripline, and micro-slot probe microcoils. It is demonstrated that planar microcoils are very very comparable to these designs in sensitivity, with the added advantage of being a flexible platform.

MS (Master of Science)
Inductive Coupling, NMR, Microfluidics
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