Sensitive NMR Sensors Detect Antibodies to Influenza

Koh, Isaac; Hong, Rui; Weissleder, Ralph; Josephson, Lee

doi:10.1002/ange.200800069

Cited by 15 publications

(19 citation statements)

References 23 publications

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“…This is partially attributable to precipitation of aggregates. Additionally, the fraction of water protons influenced by the magnetic field of the particles decreases from a certain time onwards as the aggregates continue to increase in size while their number decreases (Koh et al 2008). Although precipitation due to aggregation is problematic for these in vitro experiments, it is an intended and important mode of function for the in vivo application.…”

Section: Protease-specific Iron Oxide Particles For Imaging Protease mentioning

confidence: 99%

Bioresponsive nanosensors in medical imaging

Schellenberger

2009

J. R. Soc. Interface.

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Superparamagnetic iron oxide nanoparticles have been established as sensitive probes for magnetic resonance imaging (MRI). While the majority of specific nanosensors are based on sterically stabilized iron oxide particles, the focus of this review is on the use of very small iron oxide particles (VSOPs) that are electrostatically stabilized by an anionic citrate acid shell. We used VSOPs to develop target-specific as well as protease-activatable nanosensors for molecular MRI.

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Section: Protease-specific Iron Oxide Particles For Imaging Protease mentioning

confidence: 99%

Bioresponsive nanosensors in medical imaging

Schellenberger

2009

J. R. Soc. Interface.

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“…Of note, other assay configurations using the same DMR device can yield much higher detection sensitivities both on mass and on concentration. For example, with micrometer-sized magnetic particles, we were able to achieve detection limits of ∼1 × 10 −12 M (mouse IgG to Tag peptide)17, similar to or surpassing detection limits by ELISA (Supplementary Methods online).…”

Section: Resultsmentioning

confidence: 82%

“…These particles are expected to be more efficient at dephasing water protons, resulting in increased detection sensitivity17. Additional advances have been made in the miniaturization of the device.…”

Section: Discussionmentioning

confidence: 99%

Chip–NMR biosensor for detection and molecular analysis of cells

Lee

Sun

Ham

et al. 2008

Nat Med

Self Cite

572

512

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Rapid and accurate measurement of biomarkers in tissue and fluid samples is a major challenge in medicine. Here we report the development of a new, miniaturized diagnostic magnetic resonance (DMR) system for multiplexed, quantitative and rapid analysis. By using magnetic particles as a proximity sensor to amplify molecular interactions, the handheld DMR system can perform measurements on unprocessed biological samples. We show the capability of the DMR system by using it to detect bacteria with high sensitivity, identify small numbers of cells and analyze them on a molecular level in real time, and measure a series of protein biomarkers in parallel. The DMR technology shows promise as a robust and portable diagnostic device.A number of new diagnostic platforms have been developed to measure biomolecule abundance with high sensitivity 1 , enable early disease detection 2 and gain valuable insights into biology at the systems level 3 . Some examples include nuclear magnetic resonance (NMR) with hyperpolarized gas 4 , nanowire 5 and nanoparticle 6 sensors, surface plasmon resonance devices 7 and mass spectrometry 8 . Many of these devices and techniques, however, requiring time-consuming purification of samples typically followed by a set of amplification strategies 6 , may lack the ability for the multiplexed measurements that are desirable in identifying complex diseases 1,9 or may not be amenable for easy point-of-care translation.Here we report a chip-based DMR system for rapid, quantitative and multichanneled detection of biological targets. Using readily available magnetic nano-and microparticles as a proximity sensor to amplify molecular interactions 10 , the DMR system can perform highly sensitive (up to 1 × 10 −12 M) and selective measurements on small volumes of unprocessed biological samples. As proof of concept, we show sensitive detection of bacteria, profiling of circulating cells and multiplexed identification of different cancer biomarkers. If implemented with standard microfabrication technology, the DMR system will be a high-throughput, low-cost and portable platform for large-scale sensing.The DMR sensor strategy is based on a self-amplifying proximity assay using magnetic nanoparticles 10 . When a few magnetic nanoparticles bind their intended molecular target Correspondence should be addressed to R.W. (rweissleder@mgh.harvard.edu). Note: Supplementary information is available on the Nature Medicine website.Author Contributions: H.L. designed the device, built the DMR prototype, obtained measurements, analyzed data and wrote the manuscript. E.S. performed all chemical modifications of magnetic nanoparticles and assisted in measurements and data analysis. D.H. collaborated in the development of the NMR electronics of discrete components. R.W. conceived the project, provided overall guidance, designed experiments and targeted nanoparticles, analyzed the data and wrote the manuscript with contributions from all authors.Competing Interests Statement: The authors declare competing financial i...

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“…In addition to their robustness and specificity, the immunochromatographic test strips were able to detect 3 μg/mL in serum and 14 μg/mL in whole blood, indicating their potential field application94. Finally, through magnetic relaxation, Brucella and influenza antibodies were detected in biological samples, with sensitivities of 0.3 nM and 0.1 pM respectively96, 97.…”

Section: Approaches For Detection Of Infectious Diseasesmentioning

confidence: 97%

Emerging nanotechnology-based strategies for the identification of microbial pathogenesis

Kaittanis¹,

Santra²,

Perez³

2010

Advanced Drug Delivery Reviews

260

176

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Infectious diseases are still a major healthcare problem. From food intoxication and contaminated water, to hospital-acquired diseases and pandemics, infectious agents cause disease throughout the world. Despite advancements in pathogens’ identification, some of the gold-standard diagnostic methods have limitations, including laborious sample preparation, bulky instrumentation and slow data readout. In addition, new field-deployable diagnostic modalities are urgently needed in first responder and point of care applications. Apart from compact, these sensors must be sensitive, specific, robust and fast, in order to facilitate detection of the pathogen even in remote rural areas. Considering these characteristics, researchers have utilized innovative approaches by employing the unique properties of nanomaterials in order to achieve detection of infectious agents, even in complex media like blood. From gold nanoparticles and their plasmonic shifts to iron oxide nanoparticles and changes in magnetic properties, detection of pathogens, toxins, antigens and nucleic acids has been achieved with impressive detection thresholds. Additionally, as bacteria become resistant to antibiotics, nanotechnology has achieved the rapid determination of bacterial drug susceptibility and resistance using novel methods, such as amperometry and magnetic relaxation. Overall, these promising results hint to the adoption of nanotechnology-based diagnostics for the diagnosis of infectious diseases in diverse settings throughout the globe, preventing epidemics and safeguarding human and economic wellness.

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Sensitive NMR Sensors Detect Antibodies to Influenza

Cited by 15 publications

References 23 publications

Bioresponsive nanosensors in medical imaging

Bioresponsive nanosensors in medical imaging

Chip–NMR biosensor for detection and molecular analysis of cells

Emerging nanotechnology-based strategies for the identification of microbial pathogenesis

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