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. U., 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+(MPI)+for+NMR+and+MRI+researchers.">Magnetic Particle Imaging (MPI) for NMR and MRI researchers.</a> J. Magn. Reson. 229 (4), 116-126 (2012).</li><li>Goodwill, P. W., 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=X-space+MPI:+magnetic+nanoparticles+for+safe+medical+imaging.">X-space MPI: magnetic nanoparticles for safe medical imaging.</a> Adv. Mater. 24 (28), 3870-3877 (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><li>Gleich, B., Weizenecker, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tomographic+imaging+using+the+nonlinear+response+of+magnetic+particles.">Tomographic imaging using the nonlinear response of magnetic particles.</a> Nature. 435 (7046), 1214-1217 (2005).</li><li>Rahmer, J., Weizenecker, J., Gleich, B., Borgert, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Analysis+of+a+3-D+system+function+measured+for+magnetic+particle+imaging.">Analysis of a 3-D system function measured for magnetic particle imaging.</a> IEEE Trans. Med. Imaging. 31 (6), 1289-1299 (2012).</li><li>Goodwill, P. W., Conolly, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multidimensional+x-space+magnetic+particle+imaging.">Multidimensional x-space magnetic particle imaging.</a> IEEE Trans. Med. Imaging. 30 (9), 1581-1590 (2011).</li><li>Goodwill, P. W., Konkle, J. J., Zheng, B., Saritas, E. U., Conolly, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Projection+x-space+magnetic+particle+imaging.">Projection x-space magnetic particle imaging.</a> IEEE Trans. Med. 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. F., 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=Francisella+tularensis+detection+using+magnetic+labels+and+a+magnetic+biosensor+based+on+frequency+mixing.">Francisella tularensis detection using magnetic labels and a magnetic biosensor based on frequency mixing.</a> J. Magn. Magn. Mater. 311 (1), 259-263 (2007).</li><li>Finas, D., 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=Detection+and+distribution+of+superparamagnetic+nanoparticles+in+lymphatic+tissue+in+a+breast+cancer+model+for+magnetic+particle+imaging.">Detection and distribution of superparamagnetic nanoparticles in lymphatic tissue in a breast cancer model for magnetic particle imaging.</a> Biomed. Tech. 57, (2012).</li><li>Hong, H., Lim, J., Choi, C. -. J., Shin, S. -. W., Krause, H. -. J. <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+with+a+planar+frequency+mixing+magnetic+detection+scanner.">Magnetic particle imaging with a planar frequency mixing magnetic detection scanner.</a> Rev. Sci. Instr. 85 (1), 013705 (2014).</li><li>Haegele, 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=Toward+cardiovascular+interventions+guided+by+magnetic+particle+imaging:+First+instrument+characterization.">Toward cardiovascular interventions guided by magnetic particle imaging: First instrument characterization.</a> Magn. Reson. Med. 69 (6), 1761-1767 (2012).</li><li>Haegele, 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+imaging:+visualization+of+instruments+for+cardiovascular+intervention.">Magnetic particle imaging: visualization of instruments for cardiovascular intervention.</a> Radiology. 265 (3), 933-938 (2012).</li><li>Goodwill, P. W., Lu, K., Zheng, B., Conolly, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+x-space+magnetic+particle+imaging+scanner.">An x-space magnetic particle imaging scanner.</a> Rev. Sci. 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. ...

The overall goal of this procedure is to use two dimensional mixed magnetic detection scans to analyze thin biological samples containing nanomagnetic particles. This method can help answer key questions in the field of biochemistry and medical diagnosis such as the analysis of tissue sections employing nanomagnetic particles as a leveling compound. The main advantage of this technique is that it allows a meeting of the nanomagnetic particle distribution.Demonstrating of the procedure will be Eul-Gyoon Lim, Jae-chan Jeong and Jiho Chang, three researcher from my laboratory. The p-FMMD measurement head should be designed in accordance with the text protocols. Details are given on all the wiring and coiling specifications.Assembly and setup are detailed in the text protocol. This includes adjustment of the high frequency balance and the induced voltage. Next, the measurement electronics are set up, which includes the excitation section, the low and high frequency driver sections and the detection section of the FMMD.Following this, the preamplifier, first demodulator, intermediate amplifier with filtering, second demodulator, and final amplifier with filtering are all set up. Finally, the 2D scanner is mounted and interfaced with a computer control. For this procedure, have magnetite particles with diameters of 50 nanometers and 100 nanometers and maghemite particles of 1 micron diameter.Wash the particle stock solutions in water and collect the particles using a magnet. Discard the water and wash them each two more times. Then, dilute the particles into 25 milligrams per milliliter solutions using distilled water.From the 100 nanometer particle solution, make a five-fold dilution series for concentrations of five, one, 0.2 and 0.04 milligrams per milliliter. Next, punch out pieces of absorptive blotting paper using a biopsy punch. Then, soak the paper punches in the different 100 nanometer particle solutions for 30 seconds.After the soak, let the paper punches air dry. Next, prepare cut-out pieces of nitrocellulose that are two by 18 millimeters. Soak one piece of nitrocellulose in undiluted one micron diameter particle solution for 10 to 15 seconds, and blow dry using unheated air.Soak the other piece of nitrocellulose in two solutions of different concentrations to make a concentration gradient, and dry it like the other. Lastly, using capillary action, load a capillary tube with 30 microliters of undiluted 50 nanometer diameter particle solution. Then, load a second capillary with 10 microliters of a 20 times dilution of the same particles.The scanning direction should be the shorter of the two planar dimensions. Set the starting point and scan length using the ruler marks on the palette. Enter these values in the scanning software, then set the scan offset to be a little smaller than the achievable spatial resolution.Next, set the scanning speed with consideration of the signal reduction that occurs due to low pass filtering. Use a value between one and seven millimeters per second. Now, set the stepping distance.The total scanning time is calculated using a formula that is provided in the text protocol. Before scanning, secure the sample with adhesive tape. For the scan, generate an NVD file for the motion control program.Open the PMC motion control program and load the NVD file. Press the Home button to set the mechanical origin points. Close the motion control program and return to the scanner program.Then, execute the scans. For these scans, signal intensity was analyzed as a function of the concentration of magnetic beads and the scanning speed was 10 millimeters per minute. A strong correlation was found between the bead concentration and the signal.The relationship between the speed of the scanning stage and the signal intensity was checked using paper pellets soaked with magnetic beads. Higher signals were obtained at lower scanning speeds. Comparing the p-FMMD scan with an optical image of nitrocellulose membrane sample clearly showed the utility of p-FMMD as an MPI scanner.The broadness of the scan is due mainly to the sensitivity profile of the measurement head. Similarly, two capillaries filled with different magnetic particle concentrations were photographed and scanned by p-FMMD. Clearly, concentrations differing by a factor of 20 are easily distinguished.After watching this video, you should have a good understanding of how to analyze 10 samples containing nanomagnetic particles with the FMMD technique. Once mastered, this technique can be done in about one hour if it is performed properly. After its development, this technique paved way for the researcher in the field of biochemistry and medical diagnostics to explore the distribution of the nanomagnetic particles that rather cite specific antibodies in organ system.

frequency-mixing-magnetic-detection-scanner-for-imaging-magnetic

Research

JoVE Journal

Engineering

Measurement of Coherence Decay in GaMnAs Using Femtosecond Four-wave Mixing

The application of femtosecond four-wave mixing to the study of fundamental properties of diluted magnetic semiconductors ((s,p)-d hybridization, spin-flip scattering) is described, using experiments on GaMnAs as a prototype III-Mn-V system.&#160; Spectrally-resolved and time-resolved experimental configurations are described, including the use of zero-background autocorrelation techniques for pulse optimization.&#160; The etching process used to prepare GaMnAs samples for four-wave mixing experiments is also highlighted.&#160; The high temporal resolution of this technique, afforded by the use of short (20 fsec) optical pulses, permits the rapid spin-flip scattering process in this system to be studied directly in the time domain, providing new insight into the strong exchange coupling responsible for carrier-mediated ferromagnetism.&#160; We also show that spectral resolution of the four-wave mixing signal allows one to extract clear signatures of (s,p)-d hybridization in this system, unlike linear spectroscopy techniques.&#160;&#160; This increased sensitivity is due to the nonlinearity of the technique, which suppresses defect-related contributions to the optical response. This method may be used to measure the time scale for coherence decay (tied to the fastest scattering processes) in a wide variety of semiconductor systems of interest for next generation electronics and optoelectronics.

The technique of femtosecond four-wave mixing is described, including spectrally-resolved and time-resolved configurations. We illustrate the utility of this technique for the investigation of crucial physical properties in the III-V diluted magnetic semiconductors, afforded by its nonlinearity and high temporal resolution.

The application of femtosecond four-wave mixing to the study of fundamental properties of diluted magnetic semiconductors ((s,p)-d hybridization, ...

Phase Diagram Characterization Using Magnetic Beads as Liquid Carriers

Magnetic beads with ~1.9 &#181;m average diameter were used to transport microliter volumes of liquids between contiguous liquid segments with a tube for the purpose of investigating phase change of those liquid segments. The magnetic beads were externally controlled using a magnet, allowing for the beads to bridge the air valve between the adjacent liquid segments. A hydrophobic coating was applied to the inner surface of the tube to enhance the separation between two liquid segments. The applied magnetic field formed an aggregate cluster of magnetic beads, capturing a certain liquid amount within the cluster that is referred to as carry-over volume. A fluorescent dye was added to one liquid segment, followed by a series of liquid transfers, which then changed the fluorescence intensity in the neighboring liquid segment. Based on the numerical analysis of the measured fluorescence intensity change, the carry-over volume per mass of magnetic beads has been found to be ~2 to 3 &#181;l/mg. This small amount of liquid allowed for the use of comparatively small liquid segments of a couple hundred microliters, enhancing the feasibility of the device for a lab-in-tube approach. This technique of applying small compositional variation in a liquid volume was applied to analyzing the binary phase diagram between water and the surfactant C12E5 (pentaethylene glycol monododecyl ether), leading to quicker analysis with smaller sample volumes than conventional methods.

Here, we present a protocol to investigate multi-component phase diagrams using externally controlled magnetic beads as liquid carriers in a lab-in-tube approach. This approach can aid in applications that seek to gather further information on phase change in complex liquid systems.

Magnetic beads with ~1.9 &#181;m average diameter were used to transport microliter volumes of liquids between contiguous liquid segments with a tube for ...

Detection and Recovery of Palladium, Gold and Cobalt Metals from the Urban Mine Using Novel Sensors/Adsorbents Designated with Nanoscale Wagon-wheel-shaped Pores

Developing low-cost, efficient processes for recovering and recycling palladium, gold and cobalt metals from urban mine remains a significant challenge in industrialized countries. Here, the development of optical mesosensors/adsorbents (MSAs) for efficient recognition and selective recovery of Pd(II), Au(III), and Co(II) from urban mine was achieved. A simple, general method for preparing MSAs based on using high-order mesoporous monolithic scaffolds was described. Hierarchical cubic Ia3d wagon-wheel-shaped MSAs were fabricated by anchoring chelating agents (colorants) into three-dimensional pores and micrometric particle surfaces of the mesoporous monolithic scaffolds. Findings show, for the first time, evidence of controlled optical recognition of Pd(II), Au(III), and Co(II) ions and a highly selective system for recovery of Pd(II) ions (up to ~95%) in ores and industrial wastes. Furthermore, the controlled assessment processes described herein involve evaluation of intrinsic properties (e.g., visual signal change, long-term stability, adsorption efficiency, extraordinary sensitivity, selectivity, and reusability); thus, expensive, sophisticated instruments are not required. Results show evidence that MSAs will attract worldwide attention as a promising technological means of recovering and recycling palladium, gold and cobalt metals.

Because of the importance and extensive use of palladium, gold and cobalt metals in high-technology equipment, their recovery and recycling constitute an important industrial challenge. The metal recovery system described herein is a simple, low-cost means for the effective detection, removal, and recovery of these metals from the urban mine.

Developing low-cost, efficient processes for recovering and recycling palladium, gold and cobalt metals from urban mine remains a significant challenge in ...

Use of a Multi-compartment Dynamic Single Enzyme Phantom for Studies of Hyperpolarized Magnetic Resonance Agents

Imaging of hyperpolarized substrates by magnetic resonance shows great clinical promise for assessment of critical biochemical processes in real time. Due to fundamental constraints imposed by the hyperpolarized state, exotic imaging and reconstruction techniques are commonly used. A practical system for characterization of dynamic, multi-spectral imaging methods is critically needed. Such a system must reproducibly recapitulate the relevant chemical dynamics of normal and pathological tissues. The most widely utilized substrate to date is hyperpolarized [1-13C]-pyruvate for assessment of cancer metabolism. We describe an enzyme-based phantom system that mediates the conversion of pyruvate to lactate. The reaction is initiated by injection of the hyperpolarized agent into multiple chambers within the phantom, each of which contains varying concentrations of reagents that control the reaction rate. Multiple compartments are necessary to ensure that imaging sequences faithfully capture the spatial and metabolic heterogeneity of tissue. This system will aid the development and validation of advanced imaging strategies by providing chemical dynamics that are not available from conventional phantoms, as well as control and reproducibility that is not possible in vivo.

A multi-compartment dynamic phantom is used to simulate some biology of interest for metabolic studies using hyperpolarized magnet resonance agents.

Imaging of hyperpolarized substrates by magnetic resonance shows great clinical promise for assessment of critical biochemical processes in real time. Due ...

Resonance Fluorescence of an InGaAs Quantum Dot in a Planar Cavity Using Orthogonal Excitation and Detection

The ability to perform simultaneous resonant excitation and fluorescence detection is important for quantum optical measurements of quantum dots (QDs). Resonant excitation without fluorescence detection &#8211; for example, a differential transmission measurement &#8211; can determine some properties of the emitting system, but does not allow applications or measurements based on the emitted photons. For example, the measurement of photon correlations, observation of the Mollow triplet, and realization of single photon sources all require collection of the fluorescence. Incoherent excitation with fluorescence detection &#8211; for example, above band-gap excitation &#8211; can be used to create single photon sources, but the disturbance of the environment due to the excitation reduces the indistinguishability of the photons. Single photon sources based on QDs will have to be resonantly excited to have high photon indistinguishability, and simultaneous collection of the photons will be necessary to make use of them. We demonstrate a method to resonantly excite a single QD embedded in a planar cavity by coupling the excitation beam into this cavity from the cleaved face of the sample while collecting the fluorescence along the sample&#39;s surface normal direction. By carefully matching the excitation beam to the waveguide mode of the cavity, the excitation light can couple into the cavity and interact with the QD. The scattered photons can couple to the Fabry-Perot mode of the cavity and escape in the surface normal direction. This method allows complete freedom in the detection polarization, but the excitation polarization is restricted by the propagation direction of the excitation beam. The fluorescence from the wetting layer provides a guide to align the collection path with respect to the excitation beam. The orthogonality of the excitation and detection modes enables resonant excitation of a single QD with negligible laser scattering background.

Resonant excitation of a single self-assembled quantum dot can be achieved using an excitation mode orthogonal to the fluorescence collection mode. We demonstrate a method using the waveguide and Fabry-Perot modes of a planar microcavity surrounding the quantum dots. The method allows complete freedom in the detection polarization.

The ability to perform simultaneous resonant excitation and fluorescence detection is important for quantum optical measurements of quantum dots (QDs). ...

Near-Infrared Temperature Measurement Technique for Water Surrounding an Induction-heated Small Magnetic Sphere

A technique to measure the temperature of water and non-turbid aqueous media surrounding an induction-heated small magnetic sphere is presented. This technique utilizes wavelengths of 1150 and 1412 nm, at which the absorption coefficient of water is dependent on temperature. Water or a non-turbid aqueous gel containing a 2.0-mm- or 0.5-mm-diameter magnetic sphere is irradiated with 1150 nm or 1412 nm incident light, as selected using a narrow bandpass filter; additionally, two-dimensional absorbance images, which are the transverse projections of the absorption coefficient, are acquired via a near-infrared camera. When the three-dimensional distributions of temperature can be assumed to be spherically symmetric, they are estimated by applying inverse Abel transforms to the absorbance profiles. The temperatures were observed to consistently change according to time and the induction heating power.

A technique utilizing wavelengths of 1150 and 1412 nm to measure the temperature of water surrounding an induction-heated small magnetic sphere is presented.

A technique to measure the temperature of water and non-turbid aqueous media surrounding an induction-heated small magnetic sphere is presented. This ...

Fabrication of Magnetic Nanostructures on Silicon Nitride Membranes for Magnetic Vortex Studies Using Transmission Microscopy Techniques

Electron and x-ray magnetic microscopies allow for high-resolution magnetic imaging down to tens of nanometers. However, the samples need to be prepared on transparent membranes which are very fragile and difficult to manipulate. We present processes for the fabrication of samples with magnetic micro- and nanostructures with spin configurations forming magnetic vortices suitable for Lorentz transmission electron microscopy and magnetic transmission x-ray microscopy studies. The samples are prepared on silicon nitride membranes and the fabrication consists of a spin coating, UV and electron-beam lithography, the chemical development of the resist, and the evaporation of the magnetic material followed by a lift-off process forming the final magnetic structures. The samples for the Lorentz transmission electron microscopy consist of magnetic nanodiscs prepared in a single lithography step. The samples for the magnetic x-ray transmission microscopy are used for time-resolved magnetization dynamic experiments, and magnetic nanodiscs are placed on a waveguide which is used for the generation of repeatable magnetic field pulses by passing an electric current through the waveguide. The waveguide is created in an extra lithography step.

A protocol for the fabrication of magnetic micro- and nanostructures with spin configurations forming magnetic vortices suitable for transmission electron microscopy (TEM) and magnetic transmission x-ray microscopy (MTXM) studies is presented.

Electron and x-ray magnetic microscopies allow for high-resolution magnetic imaging down to tens of nanometers. However, the samples need to be prepared ...

A Random-displacement Measurement by Combining a Magnetic Scale and Two Fiber Bragg Gratings

Long-distance displacement measurements using optical fibers have always been a challenge in both basic research and industrial production. We developed and characterized a temperature-independent fiber Bragg grating (FBG)-based random-displacement sensor that adopts a magnetic scale as a novel transferring mechanism. By detecting shifts of two FBG center wavelengths, a full-range measurement can be obtained with a magnetic scale. For identification of the clockwise and counterclockwise rotation direction of the motor (in fact, the direction of movement of the object to be tested), there is a sinusoidal relationship between the displacement and the center wavelength shift of the FBG; as the anticlockwise rotation alternates, the center wavelength shift of the second FBG detector shows a leading phase difference of around 90&#176; (+90&#176;). As the clockwise rotation alternates, the center wavelength shift of the second FBG displays a lagging phase difference of around 90&#176; (-90&#176;). At the same time, the two FBG-based sensors are temperature independent. If there is some need for a remote monitor without any electromagnetic interference, this striking approach makes them a useful tool for determining the random displacement. This methodology is appropriate for industrial production. As the structure of the whole system is relatively simple, this displacement sensor can be used in commercial production. In addition to it being a displacement sensor, it can be used to measure other parameters, such as velocity and acceleration.

A protocol to create a full-range linear displacement sensor, combining two packaged fiber Bragg grating detectors with a magnetic scale, is presented.

Long-distance displacement measurements using optical fibers have always been a challenge in both basic research and industrial production. We developed ...

Enrich and Expand Rare Antigen-specific T Cells with Magnetic Nanoparticles

We have developed a tool to both enrich and expand antigen-specific T cells. This can be helpful in cases such as to A) detect the existence of antigen-specific T cells, B) probe the dynamics of antigen-specific responses, C) understand how antigen-specific responses affect disease state such as autoimmunity, D) demystify heterogeneous responses for antigen-specific T cells, or E) utilize antigen-specific cells for therapy. The tool is based on a magnetic particle that we conjugate antigen-specific and T cell co-stimulatory signals, and that we term as artificial antigen presenting cells (aAPCs). Consequently, since the technology is simple to produce, it can easily be adopted by other laboratories; thus, our purpose here is to describe in detail the fabrication and subsequent use of the aAPCs. We explain how to attach antigen-specific and co-stimulatory signals to the aAPCs, how to utilize them to enrich for antigen-specific T cells, and how to expand antigen-specific T cells. Furthermore, we will highlight engineering design considerations based on experimental and biological information of our experience with characterizing antigen-specific T cells.

Antigen-specific T cells are difficult to characterize or utilize in therapies due to their extremely low frequency. Herein, we provide a protocol to develop a magnetic particle which can bind to antigen-specific T cells to enrich these cells and then to expand them several hundred-fold for both characterization and therapy.

We have developed a tool to both enrich and expand antigen-specific T cells. This can be helpful in cases such as to A) detect the existence of ...

Infrared Degenerate Four-wave Mixing with Upconversion Detection for Quantitative Gas Sensing

We present a protocol for performing gas spectroscopy using infrared degenerated four-wave mixing (IR-DFWM), for the quantitative detection of gas species in the ppm-to-single-percent range. The main purpose of the method is the spatially resolved detection of low-concentration species, which have no transitions in the visible or near-IR spectral range that could be used for detection. IR-DFWM is a nonintrusive method, which is a great advantage in combustion research, as inserting a probe into a flame can change it drastically. The IR-DFWM is combined with upconversion detection. This detection scheme uses sum-frequency generation to move the IR-DFWM signal from the mid-IR to the near-IR region, to take advantage of the superior noise characteristics of silicon-based detectors. This process also rejects most of the thermal background radiation. The focus of the protocol presented here is on the proper alignment of the IR-DFWM optics and on how to align an intracavity upconversion detection system.

Here, we present a protocol to perform sensitive, spatially resolved gas spectroscopy in the mid-infrared region, using degenerate four-wave mixing combined with upconversion detection.

We present a protocol for performing gas spectroscopy using infrared degenerated four-wave mixing (IR-DFWM), for the quantitative detection of gas species ...