Mn-ferrite nanoparticles as promising magnetic tags for radiofrequency inductive detection and quantification in lateral flow assays.

Lateral flow assays are low-cost point-of-care devices that are stable, easy to use, and provide quick results. They are mostly used as qualitative screening tests to detect biomarkers for several diseases. Quantification of the biomarkers is sometimes desirable but challenging to achieve. Magnetic nanoparticles can be used as tags, providing both visual and magnetic signals that can be detected and quantified by magnetic sensors. In the present work, we synthesized superparamagnetic MnFe2O4 nanoparticles using the hydrothermal coprecipitation route. MnFe2O4 presents low magnetic anisotropy and high saturation magnetization, resulting in larger initial magnetic susceptibility, which is crucial for optimizing the signal in inductive sensors. We functionalized the coprecipitated nanoparticles with citric acid to achieve colloidal stability in a neutral pH and to provide carboxyl groups to their surface to bioconjugate with biomolecules, such as proteins and antibodies. The nanomaterials were characterized by several techniques, and we correlated their magnetic properties with their sensitivity and resolution for magnetic detection in radiofrequency inductive sensors. We considered the NeutrAvidin/biotin model of biorecognition to explore their potential as magnetic labels in lateral flow assays. Our results show that MnFe2O4 nanoparticles are more sensitive to inductive detection than magnetite nanoparticles, the most used nanotags in magnetic lateral flow assays. These nanoparticles present high potential as magnetic tags for the development of sensitive lateral flow immunoassays for detecting and quantifying biomarkers.

New Perspective on Planar Inductive Sensors: Radio-Frequency Refractometry for Highly Sensitive Quantification of Magnetic Nanoparticles.

We demonstrate how resonant planar coils may be used as sensors to detect and quantify magnetic nanoparticles reliably. A coil's resonant frequency depends on the adjacent materials' magnetic permeability and electric permittivity. A small number of nanoparticles dispersed on a supporting matrix on top of a planar coil circuit may thus be quantified. Such nanoparticle detection has application detection to create new devices to assess biomedicine, food quality assurance, and environmental control challenges. We developed a mathematical model for the inductive sensor response at radio frequencies to obtain the nanoparticles' mass from the self-resonance frequency of the coil. In the model, the calibration parameters only depend on the refraction index of the material around the coil, not on the separate magnetic permeability and electric permittivity. The model compares favourably with three-dimensional electromagnetic simulations and independent experimental measurements. The sensor can be scaled and automated in portable devices to measure small quantities of nanoparticles at a low cost. The resonant sensor combined with the mathematical model is a significant improvement over simple inductive sensors, which operate at smaller frequencies and do not have the required sensitivity, and oscillator-based inductive sensors, which focus on just magnetic permeability.

Magnetic Nanoclusters Increase the Sensitivity of Lateral Flow Immunoassays for Protein Detection: Application to Pneumolysin as a Biomarker for Streptococcus pneumoniae.

Lateral flow immunoassays for detecting biomarkers in body fluids are simple, quick, inexpensive point-of-care tests widely used in disease surveillance, such as during the coronavirus disease 2019 (COVID-19) pandemic. Improvements in sensitivity would increase their utility in healthcare, food safety, and environmental control. Recently, biofunctional magnetic nanoclusters have been used to selectively label target proteins, which allows their detection and quantification with a magneto-inductive sensor. This type of detector is easily integrated with the lateral flow immunoassay format. Pneumolysin is a cholesterol-dependent cytolysin and one of the most important protein virulence factors of pneumonia produced by Streptococcus pneumoniae. It is recognized as an important biomarker for diagnosis in urine samples. Pneumonia is the infectious disease that causes the most deaths globally, especially among children under five years and adults over 65 years, most of them in low- and middle-income countries. There especially, a rapid diagnostic urine test for pneumococcal pneumonia with high sensitivity and specificity would be helpful in primary care. In this work, a lateral flow immunoassay with magnetic nanoclusters conjugated to anti-pneumolysin antibodies was combined with two strategies to increase the technique's performance. First, magnetic concentration of the protein before the immunoassay was followed by quantification by means of a mobile telephone camera, and the inductive sensor resulted in detection limits as low as 0.57 ng (telephone camera) and 0.24 ng (inductive sensor) of pneumolysin per milliliter. Second, magnetic relocation of the particles within the test strip after the immunoassay was completed increased the detected signal by 20%. Such results obtained with portable devices are promising when compared to non-portable conventional pneumolysin detection techniques such as enzyme-linked immunosorbent assays. The combination and optimization of these approaches would have excellent application in point-of-care biodetection to reduce antibiotic misuse, hospitalizations, and deaths from community-acquired pneumonia.

Double-Layer Fatty Acid Nanoparticles as a Multiplatform for Diagnostics and Therapy.

Today, public health is one of the most important challenges in society. Cancer is the leading cause of death, so early diagnosis and localized treatments that minimize side effects are a priority. Magnetic nanoparticles have shown great potential as magnetic resonance imaging contrast agents, detection tags for in vitro biosensing, and mediators of heating in magnetic hyperthermia. One of the critical characteristics of nanoparticles to adjust to the biomedical needs of each application is their polymeric coating. Fatty acid coatings are known to contribute to colloidal stability and good surface crystalline quality. While monolayer coatings make the particles hydrophobic, a fatty acid double-layer renders them hydrophilic, and therefore suitable for use in body fluids. In addition, they provide the particles with functional chemical groups that allow their bioconjugation. This work analyzes three types of self-assembled bilayer fatty acid coatings of superparamagnetic iron oxide nanoparticles: oleic, lauric, and myristic acids. We characterize the particles magnetically and structurally and study their potential for resonance imaging, magnetic hyperthermia, and labeling for biosensing in lateral flow immunoassays. We found that the myristic acid sample reported a large r2 relaxivity, superior to existing iron-based commercial agents. For magnetic hyperthermia, a significant specific absorption rate value was obtained for the oleic sample. Finally, the lauric acid sample showed promising results for nanolabeling.