Longitudinal Multiplexed Measurement of Quantitative Proteomic Signatures in Mouse Lymphoma Models Using Magneto-Nanosensors

Abstract

Cancer proteomics is the manifestation of relevant biological processes in cancer development. Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy. To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed. However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis. Here, we present a technique based on magneto-nanosensors to longitudinally monitor the protein profiles in individual mice of lymphoma models using a small volume of a sample for multiplex assays.Methods: Drug-sensitive and -resistant cancer cell lines were used to develop the mouse models that render different outcomes upon the drug treatment. Two groups of mice were inoculated with each cell line, and treated with either cyclophosphamide or vehicle solution. Serum samples taken longitudinally from each mouse in the groups were measured with 6-plex magneto-nanosensor cytokine assays. To find the origin of IL-6, experiments were performed using IL-6 knock-out mice.Results: The differences in serum IL-6 and GCSF levels between the drug-treated and untreated groups were revealed by the magneto-nanosensor measurement on individual mice. Using the multiplex assays and mouse models, we found that IL-6 is secreted by the host in the presence of tumor cells upon the drug treatment.Conclusion: The multiplex magneto-nanosensor assays enable longitudinal proteomic studies on mouse tumor models to understand tumor development and therapy mechanisms more precisely within a single biological object.

Design of micromagnetic arrays for on-chip separation of superparamagnetic bead aggregates and detection of a model protein and double-stranded DNA analytes

“…Magnetophoretic LOC research initially focused on miniaturizing high gradient magnetic field separation due to the central role SPM beads play in in vitro diagnostics 3 , 4 , and has rapidly expanded to include a number of functions, including simultaneous detection of multiple analytes 5 – 7 . Significantly, on-chip detection technologies have been developed to count SPM beads using giant magnetoresistance 8 , tunneling magnetoresistance 9 , planar Hall magnetoresistance 10 , and optical sensing 11 . The integration of high gradient separation with these sensors promises to deliver devices that are capable of rapid and sensitive point of care testing (POCT) 12 – 14 .…”

Real-time temperature correction for magnetoresistive biosensors integrated with temperature modulator

“…These biosensors typically employ the effect of anisotropic magnetoresistance (AMR) in a simple structure ( Graham et al, 2004 ; Rizzi et al, 2014 ) or giant magnetoresistance (GMR) in a multilayered structure ( Lee et al, 2016 ; Wang et al, 2015 ). Due to the lack of magnetic contents in most biological samples, magnetic biosensors can achieve high sensitivities for many biomarkers ( Gaster et al, 2009 ; Lee et al, 2018 ; Ren et al, 2020 ). However, since magnetoresistance-based biosensors rely on electrical resistance changes upon an external magnetic field, they are inevitably vulnerable to temperature changes.…”

Magnetic supercluster particles for highly sensitive magnetic biosensing of proteins

“…Their sensitivities can be tailored by modifying the structure and geometry of the sensors and employing signal transduction tags such as magnetic nanoparticles, magnetic microbeads, or any other magnetic materials. By taking advantage of these aspects, magnetic biosensors have successfully been used in various applications including antibody monitoring [22][23][24], evaluation of protein-protein interactions [25,26], DNA mutation measurement [27], and cancer biomarker detection [28,29]. To further increase the sensitivity of magnetic biosensors, signal-generating tags are worth improving because magnetic biosensors typically detect the magnetic field from the tags attached to the target analytes rather than directly detecting the analytes themselves.…”