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

Summary

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.

Abstract

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 × 25 mm p-FMMD images acquired from samples with 1 µm 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.

Introduction

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 nanop....

Protocol

1. Design a Planar FMMD Measurement Head

1. 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.
   1. Place the excitation coils such that the directly induced signal in the pickup coils cancels out in order to prevent saturation of the preampl....

Results

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's sensitivity to a magnetic moment at each of the.......

Discussion

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·f_1<.......

Materials

List of materials used in this article

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