Draft:Magnetic Modulation Biosensing

Magnetic Modulation Biosensing (MMB) is an optical biosensing technology developed in 2008. The MMB enables rapid and highly sensitive detection of biomarkers such as proteins, nucleic acids, and antibodies, even at ultra-low concentrations. the technology is utilized in clinical diagnostics, pathogen detection, and biomedical research.​

Background

Biomarkers, such as proteins, DNA fragments, or nucleic acids, are an essential tool for the detection of various diseases. Even minor changes in biomarker concentrations may be an indication of the first signs of a disease. Due to the biomarkers' often low concentrations, sensitive detection methods are required.

In many bioligical assays, the target protein is marked with a fluorescent marker. To see the fluorescent marker, one need to shine laser light on the solution. However, at low concentrations, only two or three molecules are positioned inside the detection volume, and therefore, the fluorescence signal is very weak, which limits the minimum concentration of detection. Traditional techniques like enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) are effective but involve complex procedures and lengthy processing times.

The Magnetic Modulation Biosensing (MMB) is a high-sensitivity detection platform developed in 2008 to address these limitations. It enables rapid detection of fluorescently labeled biomarkers at low concentrations by modulating magnetic beads within a laser beam. The technology was commercialized in 2018 by MagBiosense Inc. for point-of-care diagnostic applications.

Principles of operation

The technology utilizes magnetic beads as capture surfaces to trap the fluorescently labeled target molecules.

The MMB has 2 key elements:

• Aggregation
• Modulation

Aggregation

MMB Detection process.

Using an electromagnet, the system aggregates the fluorescent-conjugated beads to increase the signal intensity.

Modulation

An alternating magnetic field, induced by the two electromagnets, moves the aggregated beads cluster in and out of a focused laser beam, generating a periodic fluorescent signal. This modulation distinguishes the target signal from the solution background noise, eliminating the need for multiple washing or separation steps.

Magnetic Modulation Biosensing optical setup.

The Optical Path

A laser beam is reshaped using two plano-convex lenses, reflected by a dichroic mirror, and focused by an objective lens onto the sample. The sample is a magnetic bead aggregate inside a rectangular glass cell positioned between two electromagnets that cause the bead aggregates to move. The laser excites the fluorophores in the sample, and the emitted fluorescence is collected by the same objective lens, filtered by an emission filter, and detected by a CCD camera or by a photomultiplier tube (PMT). A precision pinhole blocks the scattered photons from reaching the PMT.

Applications

Clinical Diagnostics

Image of a baby with microcephaly (left) compared to a normal baby (right). This is one of the potential effects of Zika virus. Signs of microcephaly may develop a few months after birth.

MMB has been applied in various clinical settings:​

• Zika Virus Detection: MMB-based serological assays targeting the Zika virus non-structural protein 1 (NS1) demonstrated 88–97% sensitivity and 100% specificity, outperforming traditional ELISA tests.

• COVID-19 Testing: An MMB-based molecular assay for detection of SARS-CoV-2 nasopharyngeal-swab-extracted -RNA achieved 97.8% sensitivity and 100% specificity, with a turnaround time of 30 minutes, significantly faster than standard Real-time polymerase chain reaction (RT-qPCR) methods.

Structure of a SARSr-CoV virion

Demonstration of a nasopharyngeal swab for COVID‑19 testing

• Interleukin-8 Detection: MMB enabled the detection of human interleukin-8 at concentrations as low as 0.08 ng/L in plasma, comparable to state-of-the-art laboratory assays .

Research Applications

In research, MMB facilitates:

• Protein-Protein Interaction Studies: MMB allows for the detection of protein interactions within two minutes, offering a faster and more sensitive alternative to traditional co-immunoprecipitation and Western blot techniques. ​
• Nucleic Acid Detection: MMB can detect specific DNA sequences with fewer PCR cycles compared to quantitative PCR, enhancing efficiency in genetic analysis.

Advantages

MMB offers several benefits over conventional biosensing methods:

• High Sensitivity: Capable of detecting biomolecules at sub-picomolar concentrations.​
• Rapid Results: Provides results within minutes, expediting diagnostic processes.
• Simplified Protocols: Eliminates the need for washing and separation steps, streamlining workflows.​
• Versatility: Applicable to a broad range of targets, including proteins, nucleic acids, and antibodies.​

See Also

• Biosensor
• Fluorescence
• Magnetic Bead

• immunoassay