Name: frequency mixing magnetic detection scanner for imaging magnetic particles in planar samples
Uploaded: 2016-06-09T14:00:00
Description: Watch this Scientific Journal Video about Frequency Mixing Magnetic Detection Scanner for Imaging Magnetic Particles in Planar Samples at JoVE.com

This work was supported by the ICT R&#38;D program of MSIP/IITP, Republic of Korea (Grant No: B0132-15-1001, Development of Next Imaging System).

1. Design a Planar FMMD Measurement Head
<ol>
	<li>Choose a coil scheme for the measurement head. Select a configuration according to Figure 1, consisting of two pickup coils above and two below the sample in a (-, +, +, -) sequence, with the sample sitting in the center between the two (+) coils. The sign denotes the direction of winding, i.e., (+) for clockwise and (-) for counterclockwise. Thus, the sensitivity of the pickup coils becomes almost homogeneous across the sample thickness.
	<ol...

<ol>
	<li>Tseng, P., Judy, J. W., Di Carlo, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+nanoparticle-mediated+massively+parallel+mechanical+modulation+of+single-cell+behavior.">Magnetic nanoparticle-mediated massively parallel mechanical modulation of single-cell behavior.</a> Nat meth. 9 (11), 1113-1119 (2012).</li><li>Borgert, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fundamentals+and+applications+of+magnetic+particle+imaging.">Fundamentals and applications of magnetic particle imaging.</a> J. Cardiovasc. Comput. Tomogr. 6 (3), 149-153 (2012).</li><li>Buzug, T. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+particle+imaging:+introduction+to+imaging+and+hardware+realization.">Magnetic particle imaging: introduction to imaging and hardware realization.</a> Z. Med. Phys. 22 (4), 323-334 (2012).</li><li>Kanger, J. S., Subramaniam, V., van Driel, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracellular+manipulation+of+chromatin+using+magnetic+nanoparticles.">Intracellular manipulation of chromatin using magnetic nanoparticles.</a> Chromosome Res. 16 (3), 511-522 (2008).</li><li>Thanh, N. T. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Magnetic Nanoparticles: From Fabrication to Clinical Applications. , (2012).</li><li>Saritas, E. 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Imaging. 31 (5), 1076-1085 (2012).</li><li>Gr&#228;fe, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+Application+Scenario+for+Single-Sided+Magnetic+Particle+Imaging.">An Application Scenario for Single-Sided Magnetic Particle Imaging.</a> Biomed. Tech. 57, (2012).</li><li>Krause, H. -. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+particle+detection+by+frequency+mixing+for+immunoassay+applications.">Magnetic particle detection by frequency mixing for immunoassay applications.</a> J. Magn. Magn. Mater. 311 (1), 436-444 (2007).</li><li>Meyer, M. H. 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Instrum. 83 (3), 033708 (2012).</li><li>Lampe, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fast+reconstruction+in+magnetic+particle+imaging.">Fast reconstruction in magnetic particle imaging.</a> Phys. Med. Biol. 57 (4), 1113-1134 (2012).</li><li>Yim, H., Seo, S., Na, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MRI+Contrast+Agent-Based+Multifunctional+Materials:+Diagnosis+and+Therapy.">MRI Contrast Agent-Based Multifunctional Materials: Diagnosis and Therapy.</a> J Nanomat. 2011 (2011), (2011).</li></ol>

The measurement technique utilizes the nonlinearity of the magnetization curve of the superparamagnetic particles. The two-sided measurement head simultaneously applies two magnetic excitation fields of different frequency to the sample, a low frequency (f2) component to drive the particles into magnetic saturation and a high frequency (f1) probe field to measure the nonlinear magnetic response. In particular, both harmonics of the incident fields, m&#183;f1<...

Magnetic nanoparticles (MNP) have found widespread applications in molecular biology and in medicine, i.e., for manipulation of biomolecules and single cells1, for selectively labeling target entities for detection,2, 3 for chromatin modulation,4 and for mRNA isolation and cancer treatment.5 Due to their superparamagnetic properties, they are especially useful for medical imaging. They can serve, for instance, as contrast agents or tracers for Magnetic Resonance Imaging (MRI) or for susceptibility imaging using Superconducting Quantum Interference Device (SQUID) detectors. 2, 6 The superparamagnetic nanoparticles yield a good contrast to the different tissues of the human body which are dia- or paramagnetic.7 Thus, the particles can conveniently be used to acquire medical images of human body parts with relatively good spatial resolution and sensitivity.8
The Magnetic Particle Imaging (MPI) technique introduced by Gleich and Weizenecker9 makes use of the nonlinearity of the particle&#39;s magnetization. At zero or weak magnetic field bias, the response of MNP to an ac excitation of frequency f is strong due to their large susceptibility. In particular, the particle&#39;s nonlinear magnetization gives rise to the generation of harmonics n&#183;f, with n = 2, 3, 4 &#8230; At high magnetic field bias, the harmonic response becomes weak because the particles are magnetically saturated. In the MPI technique, the sample is completely magnetized except for a field-free line (FFL) or a field-free point (FFP). Only particles situated close to this line or point will contribute to the nonlinear response of the sample. With the movement of a FFP and employment of suitable receiver coils, Gleich and Weizenecker acquired MPI images with a spatial resolution of 1 mm.
In order to obtain information on the spatial distribution of MNP, two methods are usually employed, the mechanical movement of the sensor with respect to the sample, or movement of the FFL/FFP by means of electromagnets.2, 3 In the latter case, image reconstruction techniques like harmonic-space MPI3 or X-space MPI10, 11, 12 are required. The spatial resolution of MPI is determined by the convolution properties of excitation and detection coils as well as by the characteristics of the magnetic field gradient. This allows image reconstruction algorithms to obtain an improved resolution over the native resolution, which is determined by size and distance of the pickup coils as well as by the magnetic field distribution governed by Maxwell&#39;s equations.
A MPI scanner is usually comprised of a strong magnet for magnetizing the whole sample, a controllable coil system for steering a FFL or FFP across the sample, a high frequency excitation coil system, and a detection coil system for picking up the nonlinear response from the sample. The FFL/FFP is continuously moved through the sample volume while the harmonic response from this unsaturated sample region is recorded. In order to avoid the problem of fitting the specimen into the scanner, a single-sided MPI scanner has been demonstrated by Gr&#228;fe et al.13, however at the expense of reduced performance. Best results are obtained if the sample is surrounded by the magnets and coils. Because the sample has to be fully magnetized except for the FFL/FFP region, the technique requires relatively large and strong magnets with water cooling, leading to a rather bulky and heavy MPI system.
Our approach is based on frequency mixing at the non-linear magnetization curve of superparamagnetic particles.14 When super-paramagnets are exposed to magnetic fields at two distinct frequencies (f1 and f2), sum frequencies representing a linear combination m&#183;f1 + n&#183;f2 (with integer numbers m, n) are generated. It was shown that the appearance of these components is highly specific to the nonlinearity of the magnetization curve of the particles.15 In other words, when the MNP sample is simultaneously exposed to a driving magnetic field at frequency f2 and a probing field at frequency f1, the particles generate a response field at frequency f1 + 2&#183;f2. This sum frequency would not be existent without the magnetically nonlinear sample, therefore the specificity is extremely high. We called this method &#34;frequency mixing magnetic detection&#34; (FMMD). It has been experimentally verified that the technique yields a dynamic range of more than four orders of magnitude in particle concentration.14
In contrast to typical MPI instrumentation, the planar frequency mixing magnetic detection (p-FMMD) approach does not require to magnetize the sample close to saturation because the generation of the sum frequency component f1 + 2&#183;f2 is maximum at zero static bias field.14 Therefore, the need for strong and bulky magnets is alleviated. In fact, the outer dimensions of the measurement head are only 77 mm &#215; 68 mm &#215; 29 mm. For comparison, MPI setups are typically meter-sized.7 The drawback, however, is that the technique is restricted to planar samples with a maximum thickness of 2 mm in the current setup. The sample has to be scanned relatively to the two-sided measurement head. A re-construction allowing for thicker samples is possible, but has to be traded in for a loss of spatial resolution.
Based on this FMMD technique, we present a special type of MPI detector for planar samples, the so-called &#34;planar frequency mixing magnetic detection&#34; (p-FMMD) scanner. The principle has been recently published.17 In this work, we focus on the methodology of the technique and present protocols how to set up such a scanner and how to perform scans. It has been shown that MPI can be applied for medical diagnostic purposes such as cardiovascular or cancer imaging.16, 18, 19 Therefore we believe that the new MPI scanner can be used for a broad range of potential applications, e.g., for measuring magnetic particle distribution in tissue slices.

<table>
	<tbody>
		<tr>
			<td>Magnetic particles &#34;SiMAG Silanol&#34;</td>
			<td>Chemicell (http://www.chemicell.com)</td>
			<td>1101-5</td>
			<td>Aqueous dispersion of magnetic silica particles, Maghemite, dia. 1 &#181;m</td>
		</tr>
		<tr>
			<td>Magnetic nanoparticles &#34;fluidMAG-Amine&#34;</td>
			<td>Chemicell (http://www.chemicell.com)</td>
			<td>4121-5</td>
			<td>Aqueous dispersion of magnetic nanoparticles, Magnetite, dia. 50 nm</td>
		</tr>
		<tr>
			<td>Microtube 10 &#181;l</td>
			<td>Hirschmann Laborger&#228;te (http://www.hirschmann-laborgeraete.de/?sc_lang=en)</td>
			<td></td>
			<td>volume 10 &#181;l, outer diameter 400 &#181;m, length 40 mm</td>
		</tr>
		<tr>
			<td>Nitrocellulose Membrane Biodyne B</td>
			<td>Thermo Scientific (http://www.thermoscientific.com)</td>
			<td>77016</td>
			<td>Biodyne B Nylon Membrane, 0.45 &#181;m, 8 cm x 12 cm</td>
		</tr>
		<tr>
			<td>DDS chip AD9834</td>
			<td>Analog Devices (http://www.analog.com)</td>
			<td>AD9834</td>
			<td>20 mW Power, 2.3 V to 5.5 V, 75 MHz Complete DDS</td>
		</tr>
		<tr>
			<td>Operational Amplifier AD829</td>
			<td>Analog Devices (http://www.analog.com)</td>
			<td>AD829</td>
			<td>High Speed, Low Noise Video Op Amp</td>
		</tr>
		<tr>
			<td>Analog Multiplier MPY634</td>
			<td>Texas Instruments (http://www.ti.com)</td>
			<td>MPY634</td>
			<td>Wide Bandwidth Precision Analog Multiplier</td>
		</tr>
		<tr>
			<td>High-Speed Buffer BUF634</td>
			<td>Texas Instruments (http://www.ti.com)</td>
			<td>BUF634</td>
			<td>250mA High-Speed Buffer</td>
		</tr>
		<tr>
			<td>Operational Amplifier OPA627</td>
			<td>Texas Instruments (http://www.ti.com)</td>
			<td>OPA627</td>
			<td>Precision High-Speed Difet(R) Operational Amplifiers</td>
		</tr>
		<tr>
			<td>Operational Amplifier TL072</td>
			<td>Texas Instruments (http://www.ti.com)</td>
			<td>TL072</td>
			<td>Dual Low-Noise JFET-Input General-Purpose Operational Amplifier</td>
		</tr>
		<tr>
			<td>Lock-In Amplifier SR830</td>
			<td>Stanford Instruments (http://www.thinksrs.com)</td>
			<td>SR830</td>
			<td>100 kHz DSP lock-in amplifier</td>
		</tr>
		<tr>
			<td>XYZ motorized stage</td>
			<td>Sciencetown, Incheon, Korea (http://mkmsll.en.ec21.com/)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cleanroom wiper</td>
			<td>Seoul Semitech Co (http://www.seoulsemi.com)</td>
			<td>CF-909</td>
			<td>dimension 2.0 mm &#215; 18 mm</td>
		</tr>
	</tbody>
</table>

frequency mixing magnetic detection scanner for imaging magnetic particles in planar samples

The setup of a planar Frequency Mixing Magnetic Detection (p-FMMD) scanner for performing Magnetic Particles Imaging (MPI) of flat samples is presented. It consists of two magnetic measurement heads on both sides of the sample mounted on the legs of a u-shaped support. The sample is locally exposed to a magnetic excitation field consisting of two distinct frequencies, a stronger component at about 77 kHz and a weaker field at 61 Hz. The nonlinear magnetization characteristics of superparamagnetic particles give rise to the generation of intermodulation products. A selected sum-frequency component of the high and low frequency magnetic field incident on the magnetically nonlinear particles is recorded by a demodulation electronics. In contrast to a conventional MPI scanner, p-FMMD does not require the application of a strong magnetic field to the whole sample because mixing of the two frequencies occurs locally. Thus, the lateral dimensions of the sample are just limited by the scanning range and the supports. However, the sample height determines the spatial resolution. In the current setup it is limited to 2 mm. As examples, we present two 20 mm &#215; 25 mm p-FMMD images acquired from samples with 1 &#181;m diameter maghemite particles in silanol matrix and with 50 nm magnetite particles in aminosilane matrix. The results show that the novel MPI scanner can be applied for analysis of thin biological samples and for medical diagnostic purposes.

Figure 5a shows the calculated sensitivity distribution of the inner double-differential detection coil as a function of the coordinates x and y in the sample plane. It was calculated in an inverse approach by determining the superposition of the magnetic fields at all points (x, y) in the central plane generated by all four detection coils. In reverse, this determines the detection coil&#39;s sensitivity to a magnetic moment at each of...

Watch this Scientific Journal Video about Frequency Mixing Magnetic Detection Scanner for Imaging Magnetic Particles in Planar Samples at JoVE.com

Frequency Mixing Magnetic Detection Scanner for Imaging Magnetic Particles in Planar Samples

A scanner for imaging magnetic particles in planar samples was developed using the planar frequency mixing magnetic detection technique. The magnetic intermodulation product response from the nonlinear nonhysteretic magnetization of the particles is recorded upon a two-frequency excitation. It can be used to take 2D images of thin biological samples.

The setup of a planar Frequency Mixing Magnetic Detection (p-FMMD) scanner for performing Magnetic Particles Imaging (MPI) of flat samples is presented. ...

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