Magnetic Techniques for Rapid Diagnostic Testing for Health Care and Environmental Monitoring

Abstract

Early detection of disease biomarkers, toxins, and infectious microorganisms is a major goal in modern health care, environmental control, and food safety to help contain and reverse illness or prevent contaminants from entering the food chain.To achieve this, materials scientists develop biosensing platforms whose requirements may differ depending on the application. When biosensing is a tool for screening or point-of-use applications (e.g., at the patient's bedside, in the industrial plant, or harsh environments), it must be fast, low-cost, and easy to use and transport. Lateral flow immunoassays (LFI) meet these requirements. They are paper-based tests, whose best-known example is the home pregnancy test, developed to detect high levels of human chorionic gonadotropin in urine. Thanks to advances in immunology, the method has been extended with great success to a large variety of targets, the most recent the rapid diagnostic tests for SARS-CoV2 [1]. There are some limitations for LFIA expansion, mainly their sensitivity and detection limit, which are not sufficient for some applications. Magnetic nanoparticles and magnetic detectors can be an excellent way to overcome such constraints.LFI (Fig. 1) uses a strip of nitrocellulose along which a liquid sample (urine, saliva, blood, serum, or plasma) can flow by capillary action. The target molecule is selectively captured on the strip by an immunological reaction and tagged by a reporter particle or enzyme that makes it detectable. For this purpose, plasmonic or fluorescent nanoparticles, visible with the naked eye, provide the positive/negative response. Although this is good enough for pregnancy, diagnoses frequently demand quantifying biomarkers, cells, bacteria, viruses, genes, or toxins. Quantification of color reporters involves image analysis, reflectance, or fluorescence measurements. However, these methods are sensitive to ambient light, humidity, and staining of the paper strip, which cause difficulties in calibration and reproducibility, especially in samples with a complex matrix [2].To improve upon this, ferrite magnetic nanoparticles are now being used as alternative LFI reporters [3]. Although their bio-functionalization can be more challenging than for plasmonic particles, their advantages are clear for many applications.First, iron oxide nanoparticles provide a brownish color that is detectable by the naked eye or on a smartphone camera image. Magnetism can be used for pre-concentration or isolation of the target analyte from the sample matrix, and the magnetic reporters can be relocated closer to the visible membrane surface to increase their visibility.Second, magnetic nanoparticles produce a magnetic perturbation that a magnetic sensor can detect without optical interference [2]. Additionally, magnetic sensors report particles not only from the paper's surface but from the entire cross-section of the strip [4]. Finally, the magnetic signal from the nanotags does not decrease significantly with time.We review the principles and design of magnetic LFI and detail the requirements for magnetic nanoparticles to be used as reporters. We address the current methods used to read their signals that do not sacrifice the simplicity and low cost of the paper-based method. As proof of how magnetic LFI can be a useful analytical tool for biomedicine and food safety applications, we give examples of pneumonia biomarker detection (Fig. 2) and toxin quantification in foods and beverages [2], [4].We acknowledge support from the Spanish Ministry of Science and Innovation (EIN2020-112354), the Principality of Asturias (IDI/2018/000185), and the Instituto Universitario de Tecnología Industrial de Asturias (SV-20-GIJÓN-1-22).  Magnetic sensor reading out of a lateral flow strip for pneumolysin detection. The calibration yields a limit of detection of 0.2 ng of protein per mL of sample. Inset: Scheme (left) and image (right) of a magnetic lateral flow immunoassay.