Magnetic Modulation Biosensing for Rapid and Homogeneous Detection of Biological Targets at Low Concentrations

Danielli, Amos; Porat, Noga; Ehrlich, Marcelo; Arie, Ady

doi:10.2174/138920110790725375

Cited by 22 publications

(19 citation statements)

References 35 publications

(49 reference statements)

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“…For instance, the detection sensitivity of fluorescent DNA sequences can be improved by 100-fold when attached to magnetic beads, which are driven in and out of the optical beam path by an AC magnetic field. [25-27] MM mechanisms for signal modulation are straightforward and adaptable to both sensor (1D) and optical imaging (2D and 3D) modalities, but so far only a handful of examples have been reported in the latter case.…”

Section: Signal Modulation Strategiesmentioning

confidence: 99%

Optical Imaging with Dynamic Contrast Agents

Wei

2011

Chemistry A European J

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Biological imaging applications often employ molecular probes or nanoparticles for enhanced contrast. However, resolution and detection are still often limited by the intrinsic heterogeneity of the Isample, which can produce high levels of background that obscure the signals of interest. In this article we describe approaches to overcome this obstacle based on the concept of dynamic contrast, a strategy for elucidating signals by the suppression or removal of background noise. Dynamic contrast mechanisms can greatly reduce the loading requirement of contrast agents, and may be especially useful for single-probe imaging. Dynamic contrast modalities are also platform-independent, and can enhance the performance of sophisticated biomedical imaging systems or simple optical microscopes alike. Dynamic contrast is performed in two stages: i) a signal modulation scheme to introduce time-dependent changes in amplitude or phase, and ii) a demodulation step for signal recovery. Optical signals can be coupled with magnetic nanoparticles, photoswitchable probes, or plasmon-resonant nanostructures for modulation by magnetomotive, photonic, or photothermal mechanisms respectively. With respect to image demodulation, many of the strategies developed for signal processing in electronics and communication technologies can also be applied toward the editing of digital images. The image processing step can be as simple as differential imaging, or may involve multiple reference points for deconvolution using cross-correlation algorithms. Periodic signals are particularly amenable to image demodulation strategies based on Fourier transform; the contrast of the demodulated signal increases with acquisition time, and modulation frequencies in the kHz range are possible. Dynamic contrast is an emerging topic with considerable room for development, both with respect to molecular or nanoscale probes for signal modulation, and also to methods for more efficient image processing and editing.

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Section: Signal Modulation Strategiesmentioning

confidence: 99%

Optical Imaging with Dynamic Contrast Agents

Wei

2011

Chemistry A European J

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“…Recently, we have demonstrated a rapid and sensitive detection method termed magnetic modulation biosensing (MMB) . In MMB, magnetic beads and fluorescently labeled probes are attached to the target analyte and form a “sandwich” complex.…”

Section: Introductionmentioning

confidence: 99%

“…A synchronous detection enables the removal of background signal from the oscillating target signal without complicated sample preparation. Implementing the MMB system as a detection method for a SHA was previously suggested , but has never been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Detecting nucleic acid fragments in serum using a magnetically modulated sandwich assay

Margulis

Ashri

Cohen

et al. 2019

Journal of Biophotonics

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We present a novel assay for rapid and highly sensitive detection of specific nucleic acid fragments in human serum. In a magnetic modulation biosensing (MMB) system, magnetic beads and fluorescently labeled probes are attached to the target analyte and form a "sandwich" complex.An alternating external magnetic field gradient condenses the magnetic beads (and hence the target molecules with the fluorescently labeled probes) to the detection volume and sets them in a periodic motion, in and out of a laser beam. A synchronous detection enables the removal of background signal from the oscillating target signal without complicated sample preparation. The high sensitivity of the MMB system, combined with the specificity of a sandwich hybridization assay, enables detection of DNA fragments without enzymatic signal amplification. Here, we demonstrate the sensitivity of the assay by directly detecting the EML4-ALK oncogenic translocation sequence spiked in human serum. The calculated limit of detection is 1.4 pM, which is approximately 150 times better than a conventional plate reader. In general, the MMB-assisted SHA can be implemented in many other applications for which enzymatic amplification, such as PCR, is not applicable and where rapid detection of specific nucleic acid targets is required.

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“…Small spherical magnetic beads—usually consisting of a paramagnetic core embedded in a non-magnetic matrix, such as a polymer or quartz [1,2]—are widely used in bioanalysis and medical applications [2,3,4,5,6]. These applications include separating target molecules from background molecules [7,8,9], investigating molecular interactions inside living cells [5,10,11], directing neuronal migration and growth [12], detecting specific proteins and DNA sequences in plasma [13,14,15,16], and reducing background in opto-chemical sensing [17]. Many of these applications require accurate manipulation of the magnetic beads on the nano and micro scales.…”

Section: Introductionmentioning

confidence: 99%

“…Danielli et al (2008) used a magnetic modulating biosensing (MMB) system to detect proteins and specific DNA sequences. In MMB, the target molecules are captured by fluorescently labeled magnetic beads that are aggregated and manipulated in and out of an excitation beam, separating their signal from that of Raman scattering of water molecules and unbound fluorescently labeled probes [13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

Configuration and Design of Electromagnets for Rapid and Precise Manipulation of Magnetic Beads in Biosensing Applications

2019

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Rapid and precise manipulation of magnetic beads on the nano and micro scales is essential in many biosensing applications, such as separating target molecules from background molecules and detecting specific proteins and DNA sequences in plasma. Accurately moving magnetic beads back and forth requires at least two adjustable magnetic field gradients. Unlike permanent magnets, electromagnets are easy to design and can produce strong and adjustable magnetic field gradients without mechanical motion, making them desirable for use in robust and safe medical devices. However, using multiple magnetic field sources to manipulate magnetic beads presents several challenges, including overlapping magnetic fields, added bulk, increased cost, and reduced durability. Here, we provide a thorough analysis, including analytical calculations, numerical simulations, and experimental measurements, of using two electromagnets to manipulate magnetic beads inside a miniature glass cell. We analyze and experimentally demonstrate different aspects of the electromagnets’ design, such as their mutual influence, the advantages and disadvantages of different pole tip geometries, and the correlation between the electromagnets’ positions and the beads’ aggregation during movement. Finally, we have devised a protocol to maximize the magnetic forces acting on magnetic beads in a two-electromagnet setup while minimizing the electromagnets’ size. We used two such electromagnets in a small footprint magnetic modulation biosensing system and detected as little as 13 ng/L of recombinant Zika virus antibodies, which enables detection of Zika IgM antibodies as early as 5 days and as late as 180 days post symptoms onset, significantly extending the number of days that the antibodies are detectable.

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Magnetic Modulation Biosensing for Rapid and Homogeneous Detection of Biological Targets at Low Concentrations

Cited by 22 publications

References 35 publications

Optical Imaging with Dynamic Contrast Agents

Optical Imaging with Dynamic Contrast Agents

Detecting nucleic acid fragments in serum using a magnetically modulated sandwich assay

Configuration and Design of Electromagnets for Rapid and Precise Manipulation of Magnetic Beads in Biosensing Applications

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