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Recent Developments in MicroNMR Recent Developments in
MicroNMR
Michael J. McCarthy, mjmccarthy@ucdavis.edu
Department of Food Science and Technology,
University of California, Davis, CA USA
and
Center for Process Analytical Chemistry
University of Washington CPAC Rome Meeting 2006
Magnetic Resonance
Place sample in magnetic field.
Sample Equilibrates
Apply energy to the sample.
Record decay of energy from the
sample.
N
S
Intensity
Place sample
in magnet
Apply
energy
RF coil
Time
Recorded
signal CPAC Rome Meeting 2006
Current MR System
superconducting magnet
2 T MRI system CPAC Rome Meeting 2006
Current MR System
permanent magnet CPAC Rome Meeting 2006
Magnetic Resonance Principles
Advantages
Noninvasive/Nondestructive
Sensitive to physical, structural, chemical properties of
materials
Signal linear from ~10 ppt to 100%
Acquire multiple quality factors simultaneously
Highly specific information on a specific nuclus (
31
P,
13
C)
Instrument has no moving parts
Disadvantages
How do we overcome these limits?
Expensive (return on investment?)
Slow compared to many production lines
Modify process (no metal) CPAC Rome Meeting 2006
Enhancements to NMR Analyses
Measurement information processing
Artificial intelligence, neural networks,
chemometric methods, experiment design
Miniaturization
Spectrometer on a chip
NeSSI Compatible
Engineered materials
Novel magnets
High homogeneity
No fringe fields
Semerjian, 1996 CPAC Rome Meeting 2006
What can microfabrication bring to on-
line NMR/MRI
Process NMR/MRI spectrometer
Capable of measurements of
Composition
Particle size
Rheological properties
Compatible with processing environment
Clean in place chemical
Liquid and particulate suspensions CPAC Rome Meeting 2006
Motivation for the micro-design
Recent works have shown that signal-to-
noise ratio (SNR) per unit mass increases
inversely proportional to the RF coil diameter
Microfabrication presents the opportunity to
put the MR analytical sensor inside the
production process (in-line control)
No process line modification
Or sensor becomes portable
Costs are reduced CPAC Rome Meeting 2006
Sensor design concept
sample flows in capillary CPAC Rome Meeting 2006
NMR/MRI
Two detection methods
Conventional induction detection
Force detection CPAC Rome Meeting 2006 CPAC Rome Meeting 2006
Advantages:
--smaller volumes
--S/N improvements
for parallel processing
of sample CPAC Rome Meeting 2006
Compare SNR for each detection method
Most interest in
samples sizes larger
than 0.5 mm
Most development
on induction
detection CPAC Rome Meeting 2006
Induction detection developments
Microfabrication for
Spectral measurements
Physical property measurements
Viscosity
Method development
Spectra in inhomogeneous fields
Magnet construction CPAC Rome Meeting 2006
5 Turn Helmholtz Coil
HPLC tubing for flow imaging CPAC Rome Meeting 2006
Micro RF coil
5 turns, average diameter is 3.5 mm, substrate thickness is
3.5 mm, trace width is 120 µm, pitch is 160 µm, trace
thickness is 15 µm CPAC Rome Meeting 2006
Current testing of microcoils
low magnetic field 0.6T
General Electric NMR spectrometer CPAC Rome Meeting 2006
Superconducting Magnet and Probe
Current testing of microcoils
0.6T superconducting magnet
compartment of microcoil in probe;
tubing for sample delivery is shown CPAC Rome Meeting 2006
Microcoil NMR spectroscopy
experiments
* Henry R. Derr, Laramie County Community College
water H
2
O
LW~0.56Hz
propanol CH
3
CH
2
CH
2
OH CPAC Rome Meeting 2006
Lab-on-a-chip NMR sensor CPAC Rome Meeting 2006
The role of gradients hardware
Resolution of images is proportional to the
strengths of generated gradient fields
Smaller coils generate stronger gradients
than bigger coils for the same electrical
currents
Better quality of images leads to higher
measurement precision CPAC Rome Meeting 2006
Microfabricated planar gradient coils
Z-gradient coil
Y-gradient coil CPAC Rome Meeting 2006
Sensor development:
In-line viscosity measurements
Pipe flow: measure fluid velocity profile
Pipe flow: measure fluid pressure drop over a straight
length of pipe
Calculate the shear stress vs. shear rate curve to
determine viscosity
Pressure Drop Velocity Profile
Shear stress
Shear rate
Shear viscosity CPAC Rome Meeting 2006
Influence of particles (material structure)
Chocolate Milk
4 Averages
Chocolate Milk
20 Averages
Solid cocoa particles in chocolate milk decrease fluid spin-spin relaxation
time and rotate in the high shear region of the flow. Both of these effects
reduce signal-to-noise ratio.
Strawberry Milk CPAC Rome Meeting 2006
Viscosity CPAC Rome Meeting 2006
Design options
Low magnetic field strength (~0.05 to 0.2 T)
Advantages
Cost
Easier to integrate into production
Disadvantages
Signal-to-noise ratio
Imaging and/or nonimaging
Higher magnetic field (~1.5 T)
Advantages
Signal-to-noise
Disadvantages
Cost
Fringe fields
Weight
Imaging/nonimaging options CPAC Rome Meeting 2006
Small permanent magnet
Magnetic Solutions
Limited (Dublin, Ireland)
74 mm ID
~0.5 Tesla field
Magnet delivered and
installation in progress
Homogeneity is not
sufficient for
spectroscopy should be
adequate for flow
imaging. CPAC Rome Meeting 2006
Spectroscopy in Inhomogeneous Magnetic
Fields
NMR Mouse Spectra
Standard Magnet Spectra CPAC Rome Meeting 2006
Importance of higher magnetic field
Signal-to-noise ratio increases rapidly with
increasing field strength (~^2)
Improved spectral resolution
better spectra
Other nuclei (C, F, Na etc)
Better spatial resolution
~25
µ
m CPAC Rome Meeting 2006
ASPeCT Magnet Technologies Ltd.
ZERO External Magnetic Field CPAC Rome Meeting 2006
Higher Field System 1.5 Tesla
No external field
Industrial grade
Currently in the
construction phase
System to be delivered
~June 2006
Current applications:
Agricultural product quality
Future applications:
from mms to 30 cm sample sizes
Photo courtesy of ASPeCT Magnet Technologies Ltd. CPAC Rome Meeting 2006 CPAC Rome Meeting 2006
RF
Receiver
RF
Receiver
System
Interface
System
Interface
ADC
ADC
Digital
Receiver
Digital
Receiver
10 MHz
Clock
10 MHz
Clock
Direct
Digital
Synthesizer
Direct
Digital
Synthesizer
Pulse
Programmer
Pulse
Programmer
Extra
Control Lines
Extra
Control Lines
External
Trigger
External
Trigger
Expansion
Port
Expansion
Port CPAC Rome Meeting 2006
NeSSI Vision of Success
We are able to
Design...
Assemble...
Configure...

...an analytical system on
our workbench.
Lego
Like Assembly
No special skills to
assemble
plug and play/self-
documenting
Fully Automated CPAC Rome Meeting 2006
Acknowledgements
Financial Support
Center for Process Analytical Chemistry, University of Washington
National Science Foundation
Students
Young-Jin Choi
Rebecca Milczarek
Artem Goloshevsky
Co-workers
Jeff Walton
Scott Collins
Jeff de Ropp
Kathryn McCarthy
ASPeCT Magnet Technologies Ltd.
Uri Rapoport
Tecmag, inc.
Paul Kanyha