Mapping of magnetic nanoparticles and cells using thin film magnetoelectric sensors based on the delta-E effect

Abstract Superparamagnetic iron oxide nanoparticles (SPIONs) are an important tool for labeling cells and tissues in many therapeutic and diagnostic applications, such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). However, these methods require large and expensive instrumentation. Here we show that our magnetic susceptibility particle mapping (MSPM) system can achieve the detection of magnetic nanoparticles in an inexpensive and small device. The system is based on magnetoelectric (ME) sensors utilizing the ΔE effect in combination with a permanent magnet that is generating a bias field for the sensor and at the same time is magnetizing the SPIONs in the sample. The permanent magnet is placed above the sensor, and the sample is rotated through the gap in between. The magnetized SPIONs in the sample generate an additional magnetic field that can be detected by the ME sensor. The clear novelty of our approach is the use of a rotating sample, generating a periodic signal, which enables an easy separation of the desired signal from the background signal and the possibility to compensate drift, which is commonly observed in ME sensor measurements. With this improvement and the use of a ME sensor that is sensitive for low frequencies the setup is able to measure significantly smaller amounts of magnetic nanoparticles than previous approaches described in the literature and we are even able to reconstruct 2D nanoparticle distributions. The noise floor, also referred to as limit of detection (LOD), of this measurement system is around 500 pT/(Hz)1/2. The detection threshold of our MSPM system is 20 μg SPIONs in a volume of 200 mm3 and the spatial resolution is in the range of a few mm. The spatial resolution is determined by reconstructing the particle distribution in the sample layer by solving the inverse problem. To demonstrate the feasibility of the method for detecting living cells, we measured the field distribution originating from SPION-labeled fibroblast cells in an alginate-gelatin matrix, thus demonstrating the potential of our method for biomaterial applications.