Implementation of Force Differentiation in the Immunoassay

G, Lee; Metzger, Steven; Natarajan, Mohan; Yanavich, Carolyn; Dufrêne, Yves F.

doi:10.1006/abio.2000.4844

Cited by 65 publications

(40 citation statements)

References 41 publications

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“…A magnetic field gradient can be applied to attract magnetic beads to the chip or to selectively pull off only those beads not bound to the surface by specific binding. The field can be generated by external permanent magnets or electromagnets (Lee et al 2000), electromagnets integrated with the chip (Edelstein et al 2000), or by current-carrying lines positioned close to the chip (Lagae et al 2002). Bound beads are detected by the GMR sensors by applying a uniform magnetic field perpendicular to the substrate, imposing a magnetic moment to the superparamagnetic beads.…”

Section: Magnetic Beads As Labels For Detectionmentioning

confidence: 99%

Magnetic bead handling on-chip: new opportunities for analytical applications

Gijs

2004

Microfluid Nanofluid

497

555

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This review describes recent advances in the handling and manipulation of magnetic particles in microfluidic systems. Starting from the properties of magnetic nanoparticles and microparticles, their use in magnetic separation, immuno-assays, magnetic resonance imaging, drug delivery, and hyperthermia is discussed. We then focus on new developments in magnetic manipulation, separation, transport, and detection of magnetic microparticles and nanoparticles in microfluidic systems, pointing out the advantages and prospects of these concepts for future analysis applications.

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Section: Magnetic Beads As Labels For Detectionmentioning

confidence: 99%

Magnetic bead handling on-chip: new opportunities for analytical applications

Gijs

2004

Microfluid Nanofluid

497

555

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“…Factors that determine the optimal bead size include the settling times for suspended beads (i.e. their buoyancy), the magnitude of the force that can be applied to the settled beads (to discriminate against biochemical background [12,19]), and the sensor response. As discussed previously, we have evaluated a number of commercial paramagnetic particles and currently use Dynal M-280 beads [2].…”

Section: Magnetic Bead Criteriamentioning

confidence: 99%

“…We then apply a magnetic field gradient to create a controlled vertical force on each bead that selectively pulls off only those beads not bound to the surface by specific binding. This force discrimination assay increases the sensitivity of detection by greatly reducing the background bead density and thereby permitting very low bead densities to be detected with confidence [12,19]. Finally, an AC magnetic field is applied, magnetizing the beads to generate sensing fields.…”

Section: Introductionmentioning

confidence: 99%

Design and performance of GMR sensors for the detection of magnetic microbeads in biosensors

Rife

Miller

Sheehan

et al. 2003

Sensors and Actuators A: Physical

348

192

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“…Several bioassay methods have been developed that exploit this differential in binding by applying magnetic forces to microparticle labels, a technique known as magnetic force discrimination (MFD) (Baselt et al, 1998;Edelstein et al, 2000;Lee et al, 2000;Rife et al, 2003). With commercially available paramagnetic microbeads and simple magnetic geometries, MFD forces are limited to ~1 pN; therefore, the nonfouling properties of the substrate must be very tightly controlled for MFD to be effective.…”

Section: Resultsmentioning

confidence: 99%

“…However, we find microbead labels offer two significant advantages over smaller labels that far outweigh any disadvantages from the size mismatch. First, it is far simpler to detect low numbers of microbeads than molecular fluorophores, chromophores, or nanoparticles, with individual microbeads readily counted with routine optical microscopy (Lee et al, 2000;Mulvaney et al, 2004) or magnetic detection (Rife et al, 2003;Rife and Whitman, 2004). Second, and more significantly, we find that if a controlled laminar flow is maintained at the capture surface, fluidic drag forces can be applied to the microbead labels to preferentially remove nonspecifically bound labels and thereby dramatically improve the assay performance (Rife and Whitman, 2004).…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Near Infrared Imaging of Pathophysiological Changes Within the Breast

Yalavarthy¹

2008

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A significant challenge for all biosensor systems is to achieve high assay sensitivity and specificity while minimizing sample preparation requirements, operational complexity, and sample-to-answer time. We have achieved multiplexed, unamplified, femtomolar detection of both DNA and proteins in complex matrices (including whole blood, serum, plasma, and milk) in minutes using as few as two reagents by labeling conventional assay schemes with micrometerscale magnetic beads, and applying fluidic force discrimination (FFD). In FFD assays, analytes captured onto a microarray surface are labeled with microbeads, and a controlled laminar flow is then used to apply microfluidic forces sufficient to preferentially remove only nonspecifically bound bead labels. The density of beads that remain bound is proportional to the analyte concentration and can be determined with either optical counting or magnetoelectronic detection of the magnetic labels. Combining FFD assays with chip-based magnetoelectronic detection enables a simple, potentially handheld, platform capable of both nucleic acid hybridization assays and immunoassays, including orthogonal detection and identification of bacterial and viral pathogens, and therefore suitable for a wide range of biosensing applications. Report Documentation Page Form Approved OMB No. 0704-0188Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. A significant challenge for all biosensor systems is to achieve high assay sensitivity and specificity while minimizing sample preparation requirements, operational complexity, and sample-to-answer time. We have achieved multiplexed, unamplified, femtomolar detection of both DNA and proteins in complex matrices (including whole blood, serum, plasma, and milk) in minutes using as few as two reagents by labeling conventional assay schemes with micrometerscale magnetic beads, and applying fluidic force discrimination (FFD). In FFD assays, analytes captured onto a microarray surface are labeled with microbeads, and a controlled laminar flow is then used to apply microfluidic forces sufficient to preferentially remove only nonspecifically bound bead labels. The density of beads that remain bound is proportional to the analyte concentration and can be determined with either optical co...

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Implementation of Force Differentiation in the Immunoassay

Cited by 65 publications

References 41 publications

Magnetic bead handling on-chip: new opportunities for analytical applications

Magnetic bead handling on-chip: new opportunities for analytical applications

Design and performance of GMR sensors for the detection of magnetic microbeads in biosensors

Three-Dimensional Near Infrared Imaging of Pathophysiological Changes Within the Breast

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