Monte Carlo simulation of micro-x-ray fluorescence (μ-XRF) based detection of immunomagnetically labeled tumor cells

Objective. Circulating tumor cells (CTCs) carry crucial information related to the spreading and proliferation of tumors, especially at early stages of the disease. Despite the huge clinical potential held by CTCs in cancer therapy, capture and detection of these cells from the patient's peripheral blood system is rather challenging since CTCs are extremely rare cells. The objective of this paper is, based on Monte Carlo simulations, to propose the detection of immunomagnetically labelled tumor cells by micro-x-ray fluorescence (μ-XRF).Approach. The simulations were carried out with the Monte Carlo N-Particle, version 6.2, (MCNP6.2) code. The model simulates 20μm cancer cell lines and 10μm CTCs tagged with Fe₃O₄@SiO₂spherical nanoparticles of diameters 25 nm, 60 nm and 110 nm. A 17.5 keV monochromatic, micro-focused x-ray beam of diameter 15μm, impinges on cancer cells immersed in a phosphate-buffered saline solution. The simulations also include a polymeric sample holder and a silicon drift detector with a beryllium window and silver collimator.Main results. The results show the dependence of the signal intensity (Fe Kαline) on cell and nanoparticle sizes. Samples containing two and three CTCs were also simulated in particular geometrical configurations. It is presented how the inter-cell distances and cell positions relative to the incident x-ray beam affect the signal. In addition, within the parameters used in the simulations,μ-XRF method provides a minimum detection limit of 9.4 pg of Fe, which corresponds to detecting a single 10μm CTC labeled with 110 nm Fe₃O₄@SiO₂nanoparticles at 6.3% binding.Significance. Theμ-XRF based method proposed in this paper for detecting CTCs, combined with immunomagnetic nanoparticles (NPs), has the potential to be innovative in the field of liquid biopsy.