A Magnetometer Cooled with Liquid Nitrogen for the Characterization and Quantification of Magnetic Nanoparticles in Biological Samples at Room Temperature

摘要

For several medical applications of magnetic nanoparticles (MNP) it is desired to know the quantity and characteristics of the particles in the tissue of interest. That can either be necessary to determine how successful a procedure was of how it will be. Therefore a system is built, that is suitable to analyze small intact biological samples at room temperature. The magnetometer is used for the analysis and selection of sentinel lymph nodes in colorectal cancer. In this clinical procedure MNPs are administered in the resected part of the colon to determine the sentinel lymph node. The magnetometer is based on copper wound coils and comprises of two detection coils in series opposition, enclosed by two separately driven excitation coils. The detection coils are wound on a vacuum insulated sample tube with 11 mm inner diameter. To increase sensitivity and both mechanical and electrical stability of the system, the excitation and detection coils are cooled in liquid nitrogen at 77 K. By stabilization of the thermal expansion in the coil set, drift and offset components in the detection signal are reduced [1]. The systems output drift over a few hours of operation was less than 20 pV h-1. Furthermore, thermal noise in the passive detection coils is reduced, theoretically with a factor 5.4, which improves the detection limit of MNPs. To keep the sample at room temperature, the sample tube is built as an anti-cryostat using an internal heater and vacuum insulation. The magnetometer provides both simple AC-magnetometry with frequency sweeps, as well as frequency mixing detection using excitation fields with two different frequencies. Earlier experiments with sentinel lymph nodes in a vibrating sample magnetometer (VSM) revealed that iron content in the order of 1-100 pg can be significantly dominated by linear diamagnetic contributions from (fat) tissue. The frequency mixing approach enables specific quantification of the MNP content in a sample, since the linear magnetic contributions of tissue and sample holder are not contributing to the mixing component' in the detection signal [2]. As a specific frequency mixing detection algorithm, one of the excitation fields is applied as a DC-field (B - 17 mT) that is switched on and off. Caused by the non-linear response of MNPs to the excitation field, the detected response to the AC-field is different for both situations. This sample response modulation with the switch of the DC-field is used as a measure of the content of MNPs. To conclude, this magnetometer provides accurate measurement of MNPs in intact biological samples with a high stability and specificity. Because additional sample processing is not required, the measurements do not interfere with possible other (clinical) analyses. Furthermore the measurement time of less than 1 minute per sample makes the system already suitable for clinical selection of the sentinel lymph node from a series of harvester lymph nodes.