Recent Advances in Rapid and Highly Sensitive Detection of Proteins and Specific DNA Sequences Using a Magnetic Modulation Biosensing System

Abstract

In early disease stages, biomolecules of interest exist in very low concentrations, presenting a significant challenge for analytical devices and methods. Here, we provide a comprehensive overview of an innovative optical biosensing technology, termed magnetic modulation biosensing (MMB), its biomedical applications, and its ongoing development. In MMB, magnetic beads are attached to fluorescently labeled target molecules. A controlled magnetic force aggregates the magnetic beads and transports them in and out of an excitation laser beam, generating a periodic fluorescent signal that is detected and demodulated. MMB applications include rapid and highly sensitive detection of specific nucleic acid sequences, antibodies, proteins, and protein interactions. Compared with other established analytical methodologies, MMB provides improved sensitivity, shorter processing time, and simpler protocols.

Using Temporally and Spatially Resolved Measurements to Improve the Sensitivity of Fluorescence-Based Immunoassays

“…To date, the MMB system has demonstrated rapid and high analytical sensitivity in multiple serological and molecular assays, such as for Zika [21] and SARS-CoV-2 [23]. A recent review of MMB technology extensively discussed its advantages (e.g., high analytical and clinical sensitivity, simple protocol, and relatively short time-to-result) as well as its limitations (e.g., low throughput, the requirement for a specific sample holder, and the use of relatively bulky electromagnets) [22].…”

“…Recently, we presented a novel technology, termed magnetic modulation biosensing (MMB), and demonstrated its analytical and clinical sensitivity in various serological [21,22] and molecular assays [23], including assays for Zika and SARS-CoV-2. In an MMBbased assay, magnetic beads and fluorescently labeled probes are attached to the target analyte to form a "sandwich" (Figure 1a) [24].…”

“…The alternating field gradient sets them in periodic motion in and out of the laser beam, and thereby enables the removal of the constant background signal from the oscillating target signal without complicated sample preparation. Thus, MMB-assisted assays are characterized by both high sensitivity and shorter and less work-intensive testing protocols [22]. For example, using the MMB system, we detected human interleukin 8 (IL-8) within 15 min and demonstrated a limit of detection (LoD) of 0.08 ng/L and a 4-log dynamic range, much better than the state-of-the-art ELISA (1.5 ng/L LoD and 2-log dynamic range) [24].…”

“…The results demonstrate that the new algorithms offer a 2-4-fold improvement in the limit of detection (LoD), while maintaining or enhancing quantitative resolution (QR). While the MMB system provides the highly sensitive detection of various target molecules, it currently relies solely on time-resolved measurements [21][22][23][24]. Despite the 2D information collected by the camera, the signal processing algorithm ignores the spatially resolved information and simply sums up all the fluorescent signals captured by the camera, similar to a photodetector.…”