Magnetic Relaxation Switch Detection of Human Chorionic Gonadotrophin

Abstract

Functionalized nanoparticle contrast agents, also known as magnetic relaxation switches (MRS), were prepared to detect protein A and the beta subunit of human chorionic gonadotrophin (hCG-beta). Antibodies were attached to cross-linked iron oxide (CLIO) nanoparticles using standard peptide chemistry. Protein A was used as a simple model analyte, as it is naturally multivalent and can bind multiple CLIO-IgG simultaneously. The addition of PA to CLIO-IgG resulted in transverse relaxation time (T2) shortening compared to a blank control as seen by NMR relaxometry measurements. Analyte-induced aggregation was confirmed by light scattering particle size analysis. A two-particle system was designed to measure hCG-beta, as it is not multivalent and requires conjugation of a matched pair of monoclonal antibodies to CLIO (referred to as C95 and C97). Measurement of hCG-beta is important, as elevated serum levels are associated with malignancies including testicular and ovarian cancers. The addition of hCG-beta to C95 and C97 resulted in T2 shortening with a linear dynamic concentration range of 0.1 to 1 molecules of analyte per nanoparticle. Similar data were obtained for the hCG dimer. Observations with higher stoichiometric ratios of analyte to nanoparticle and increased nanoparticle valency were also made. This method can potentially be adapted to detect other biomarkers in solution.

Particles and microfluidics merged: perspectives of highly sensitive diagnostic detection

“…“Clickable” cross-linked iron oxide (CLIO) NPs are also appropriate for MRS applications because they are sufficiently stable to permit a variety of surface chemistries [51, 52]. CLIO surfaces have been designed to detect ions [53], DNA [46, 50, 54], proteins [50, 54, 55] and bacteria, as well as mammalian cells [56]. A particularly valuable system for the study of MRS is the reaction of NPs displaying the Tag peptide and reacting to a monoclonal antibody (anti Tag) binding to the peptide [48].…”

Porous Silicon Platform for Optical Detection of Functionalized Magnetic Particles Biosensing

“…[22][23][24][25][26][27][28] Recently, our group proposed and demonstrated combining PSi with biologically functionalized nanometer superparamagnetic beads (SPBs) for rapid and one-step immunoassaying. 29 surfaces of SPBs including DNA, RNA, anti-body and anti-gen. [33][34][35][36][37][38][39] Furthermore, utilizing SPBs has many advantages over non magnetic counterparts including magnetically induced collection, manipulation and immobilization, a stable magnetic signal that permeates liquids and surrounding materials, and large surface area. [40][41][42] Pil Ju Ko received his Ph.D. degree in Electrical and Electronic Engineering from Tokyo Institute of Technology, Japan (2012).…”

Multimodal Imaging and Therapy with Magnetofluorescent Nanoparticles

“…While iron oxides (magnetite [Fe 3 O 4 ] and maghemite [␥ -Fe 2 O 3 ]) have been utilized for magnetic separations for fifty years, it was not until 1978 that Ohgushi demonstrated that they were capable of shortening the relaxation times of water in a controlled and useful manner [2]. Aside from their use in magnetic resonance imaging (MRI), iron oxide nanoparticles have been used in a number of other applications, including hyperthermia [3,4], as spoilers in magnetic resonance spectroscopy [5], and as sensors for metabolites and other biomolecules [6][7][8][9][10]. In this chapter we discuss the targeting of multifunctional multimodal magnetic nanoparticles, including the relevant chemistries and properties of iron oxides by doping the particle core with dicationic metal ions, such as Co 2+ , Fe 2+ , Mn 2+ , or Ni 2+ [15].…”