Micro and Nano Scale NMR

Technologies and Systems

Jens Anders, Jan G. Korvink, Jens Anders, Jan G. Korvink, Oliver Brand, Gary K. Fedder, Christofer Hierold, Osamu Tabata

• Publisher: Wiley-VCH
• Year: 2018
• Print ISBN: 9783527340569
• eBook ISBN: 9783527697335
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Physics
• Index: Physics

This must-have book is the first self-contained summary of recent developments in the field of microscale nuclear magnetic resonance hardware, covering the entire technology from miniaturized detectors, the signal processing chain, and detection sequences. Chapters cover the latest advances in interventional NMR and implantable NMR sensors, as well as in using CMOS technology to manufacture miniaturized, highly scalable NMR detectors for NMR microscopy and high-throughput arrays of NMR spectroscopy detectors.

1
Magnets for Small‐Scale and Portable NMR

Bernhard Blümich¹, Christian Rehorn¹ and Wasif Zia²

¹RWTH Aachen University, Institut für Technische und Makromolekulare Chemie, Worringerweg 2, 52074 Aachen, Germany

²Sir Peter Mansfield Imaging Center, University of Nottingham, United Kingdom

1.1 Introduction

Nuclear magnetic resonance (NMR) exploits the resonance of the precessing motion of nuclear magnetization in magnetic fields [1, 2]. From the measurement methodology, three groups of common techniques of probing resonance can be assigned: those employing forced oscillations, free oscillations, and interferometric principles [3]. In either case, the sensitivity depends on the strength of the nuclear magnetic polarization, which, in thermodynamic equilibrium at temperatures higher than few degrees above absolute zero, is in good approximation proportional to the strength of the magnetic field. In recognition of this fact, one guideline in the development of NMR magnets has always been to reach high field strength. The highest field strength of temporally stable magnetic fields today is achieved with superconducting electromagnets. This is why most standard NMR instruments used for NMR spectroscopy in chemical analysis and magnetic resonance imaging (MRI) in medical diagnostics employ superconducting magnets cooled to the low temperature of boiling helium with cryogenic technology.

Another force driving the development of high‐field magnets is that the frequency range of the chemical shift is also proportional to the field strength. The wider the frequency range, the more complicated are the molecules that can be analyzed by NMR spectroscopy. High magnetic fields are most crucial in structural biology [4]. In chemistry and biology, molecules are mostly studied in liquid solutions. The NMR spectra of such molecules can show hundreds of narrow resonance lines, which can be better separated at high field, provided the magnetic field is sufficiently homogeneous. Else, the resonance lines from different volume elements of the sample shift and the sum spectrum measured from all volume elements show small and broad peaks instead of narrow and tall peaks (Figure 1.1c vs e). In either case, the peak area is determined by the number of nuclei resonating in the given frequency range, and the resonance frequency ν is determined by the strength B of the magnetic field, which is experienced by the nuclei (Figure 1.1),

(1.1)

where γ is the gyromagnetic ratio of the nucleus under observation.

Figure 1.1 NMR in inhomogeneous and in homogeneous fields. (a) Magnetic field strength B linearly varying with pixel position x. (b) Three pixels containing different numbers of NMR‐active nuclei at different positions x. (c) NMR spectrum observed in an inhomogeneous field (gray). For the case that the magnetic field B is homogeneous across each pixel (broken lines in a), the peak integral is proportional to the total magnetization at each pixel (black). (d) Spatially homogeneous magnetic field. (e) In a homogeneous field, the resonance signals from each pixel sum up at the same frequency.

In NMR spectroscopy, the frequency range of the signal‐bearing nuclei depends on the nuclide. Small‐scale instruments use permanent magnets with low field strengths so that their sensitivity is low, unless the nuclear polarization is enhanced by hyperpolarization methods [3, 5]. The most sensitive, stable NMR nuclei are ¹H and ¹⁹F. ¹H is the most abundant element in the universe and is found in water and organic matter. It has a frequency range of

, where ppm denotes

. ¹⁹F, on the other hand, is similarly sensitive but with a much wider frequency range of

. It is frequently encountered in pharmaceutical compounds and can be detected against a ¹H signal background due to its resonance frequency being 40 MHz at

versus 42 MHz for ¹H. Thus, both types of nuclei are of great interest also for miniature NMR devices.

To resolve individual resonance lines within these frequency ranges, the magnetic field needs to be homogeneous with an accuracy of 0.1–0.01 ppm across the sample extension for ¹H and with a factor of about 10 less for ¹⁹F (Fig. 1.1d). This magnetic field homogeneity defines a design goal for spectroscopy‐grade permanent NMR magnets. In terms of the magnetic field varying linearly along the space direction x across a 5 mm diameter sample, the field gradient

should consequently be smaller than for

for ¹H (Figure 1.1a). Note that this is two orders of magnitude less than the minimum gradient required to resolve structures in NMR imaging of soft matter at the 1 mm scale at 1 T where one deliberately applies linear magnetic field profiles across the object to measure projections of the magnetization density in terms of NMR spectra.

If the field inhomogeneity is higher, NMR spectra cannot be resolved, but NMR relaxation can still be measured by echo techniques [1, 2, 6]. In fact, NMR relaxometry experiments can be executed in arbitrarily inhomogeneous magnetic fields, where the NMR signal is spread over wide frequency ranges (Fig. 1.1c). The signal amplitude is then limited by the excitation bandwidth, whic...

Table of contents

• Cover
• Table of Contents
• Editor's Preface
• Series Editor's Preface
• Chapter 1: Magnets for Small‐Scale and Portable NMR
• Chapter 2: Compact Modeling Techniques for Magnetic Resonance Detectors
• Chapter 3: Microarrays and Microelectronics for Magnetic Resonance
• Chapter 4: Wave Guides for Micromagnetic Resonance
• Chapter 5: Innovative Coil Fabrication Techniques for Miniaturized Magnetic Resonance Detectors
• Chapter 6: IC-Based and IC-Assisted NMR Detectors
• Chapter 7: MR Imaging of Flow on the Microscale
• Chapter 8: Efficient Pulse Sequences for NMR Microscopy
• Chapter 9: Thin-Film Catheter-Based Receivers for Internal MRI
• Chapter 10: Microcoils for Broadband Multinuclei Detection
• Chapter 11: Microscale Hyperpolarization
• Chapter 12: Small-Volume Hyphenated NMR Techniques
• Chapter 13: Force-Detected Nuclear Magnetic Resonance
• Index
• End User License Agreement