sensitivity enhancement in microcoil nmr · placed inside the bore of the magnet. the fringe-field...

Michael McCarthy, Jeffrey Walton and Sandra Garcia, Department of Food Science and Technology

University of California, Davisand

Center for Process Analytical ChemistryUniversity of Washington

Songi HanDepartment of Chemistry and Biochemistry

University of California, Santa Barbara

CPAC Rome Meeting 2008

Magnetic ResonancePlace sample in magnetic field.

Sample EquilibratesApply energy to the sample.Record decay of energy from the sample.

N S

Intensity

TimePlace sample in magnet

Applyenergy

Recordedsignal

RF coil


AdvantagesNoninvasive/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 (31P,13C)

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)

Low mass sensitivity

Magnetic Resonance Principles


Measurement information processing◦ Artificial intelligence, neural networks, chemometric

methods, experiment designMiniaturization◦ ‘Spectrometer on a chip’◦ NeSSI CompatibleEngineered materials◦ Novel magnets

High homogeneityNo fringe fields

Semerjian, 1996


Process NMR/MRI spectrometer ◦ Capable of measurements of

CompositionParticle sizeRheological properties

◦ Compatible with processing environmentClean in place chemicalLiquid and particulate suspensions


Recent works have shown that signal-to-noise ratio (SNR) per unit mass increases inversely proportional to the RF coil diameterMicrofabrication presents the opportunity to put the MR analytical sensor inside the production process (in-line control)◦ No process line modification◦ Or sensor becomes portableCosts are reduced


Two detection methods◦ Conventional induction detection

Measurement of AC induced voltage◦ Force detection

Measurement of oscillator motion


Madsen, Leskowitz and Weitekamp PNAS 2004


Advantages:--smaller volumes--S/N improvementsfor parallel processingof sample


Compare SNR for each detection method

Most interest in samples sizes larger than 0.5 mm

Most development on induction detection

Incorporate DNPLow field High Sensitivity NMR SpectraBench top Metabolomics


Strawberry Milk 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.

No Field ω γ0 0= B

2X1020

Spins

1.00002X1020 1.002X1020

0.99998X1020 0.998X1020

Protons Electrons

Population Difference: 3.2X1015 4.5X1017


R- S I

Electron Spin Nuclear Spin

Stable radical


E

NMR signal is proportional to the population difference of the spins aligned with the magnetic field and those aligned against the field.

At ambient temperature the population difference is very small thus NMR is very insensitive.

DNP can polarize the nuclear spins to increase the NMR signal.


- +

+ -

- -

+ +

S Iω1+ω0

ω1+ω0

ω2 ω0

pp

Coupled Electron/Proton System

Exciting the electric spin transition p, creates a non equilibrium population distribution of the electrons spin.

Cross relaxation terms transfer the spin polarization from the electron to the proton spin.


First Observed in 7LiB0 = 30 Gaussυe = 84 MHzυLi = 50 KHzPolarization Enhancement

~ 100

Carver, T.R. & Slichter, C.P. Polarization of Nuclear Spins in Metals. Physical Review 92, 212-213 (1953).

I

SfsEγγ

ρ−=1

ρ

f

s

I and γγ S

is the coupling factor between the electron and nuclear spins

is the leakage factor and describes the electron’s ability to relax the nucleus

describes saturation of the electron and depends on radiationpower

are the gyromagnetic ratios of the electron and nucleus respectively


1. Microwave source for electron irradiation.

2. Mix source with 100 kHz for detection.

3. Irradiate radicals. When on resonance no signal will be reflected.

4. Mix down to recover 100 kHz.

5. Detect voltage of 100 kHz.

1

2

3

45

B

1.7 MHz proton and 1.12 GHz electron frequency Haulbach magnet.

Large Bore gives ample room for EPR and NMR probes.

Kia spectrometer from Magritek 1-5 MHz.


R-

R-

R-

s

s

s

R- s

H2O

H2OH2O

H2O

H2O

H2O

H2O

H2O

H2O

DNP enhancement can occur with radicals free in the solution.

Advantage: no flow apparatusnecessary

Drawback: NMR lines will be Significantly broader because of the radicals


R-

R-

R-

R- s

s

s

s

H2O

H2OH2O

H2O

H2OH2O

H2O

H2O

H2O

FLOW

DNP enhancement can occur with radicals immobilized onto a matrix.

Advantage: Enhancement yields a polarized-radical-free solution.

Drawback: Polarization may be lost due to flow.


DNP at 0.04 T Detect at 1 T

Flow sample to higher field for greater spectral resolution


Polarized water can provide contrastif water is already present in a system

Water enhanced by a factor of 24

Radicals are immobilized thus thewater contains no radicals

The contrast can be switched on andoff by turning the power on and off.

ER McCarney, S. Han, Journal of Magnetic Resonance 190 (2008) 307-315

http://www.chem.ucsb.edu/~hangroup/research_files/RELIC.htm

Ardenkjaer-Larsen, J.H., Fridlund, B., Gram, A., Hansson, G., Hansson, L., Lerche, M.H., Servin, R., Thaning, M. & Golman, K. PNAS 100, 10158 (2003).

L. Frydman and D. Blazina, Nature Physics 3, 415 (01 Jun 2007) Letters

DNP @ 1.2K~15 mM Trityl radicalTransfer sample < 6 sec

L. Frydman and D. Blazina, Nature Physics 3, 415 (01 Jun 2007) Letters


Songi Han’s DNP development is aimed atbuilding a DNP apparatus which can beplaced inside the bore of the magnet.

The fringe-field of the magnet will be usedto DNP polarize the sample in contact witha radical of choice by means of amoderate-power W-band microwavesource which is lead into the samplelocation by a wave guide.

A cryostat, a sample shuttling device and aquick heating device (hot wire heating orCO2 laser-heating through special waveguides) are the other main components ofthis apparatus.


2,2,6,6-tetramethylpypiridine-1-oxyl (TEMPO) radicals


Sample does not contain free radicalsSample heating effects are expected to be minimalEase of utilizationEase of incorporation◦ Compatible with unilateral magnets as well as

traditional magnets



Financial Support◦ Center for Process Analytical Chemistry, University of Washington◦ National Science Foundation◦ Aspect Magnet TechnologiesStudents◦ Young-Jin Choi◦ Rebecca Milczarek◦ Artem GoloshevskyCo-workers◦ Jeff Walton◦ Scott Collins◦ Songi Han◦ Sandra GarciaASPeCT Magnet Technologies Ltd. (www.aspect-mr.com)◦ Uri RapoportMagritek (www.magritek.com)

sensitivity enhancement in microcoil nmr · placed inside the bore of the magnet. the fringe-field...

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