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Nanoscience enables ultrasensitive detection of Alzheimer's biomarker

Christine D. Keating . PNAS 2005, 102, No. 7, 2263 –2264 Jwa-Min Nam, Shad Thaxton, Chad A. Mirkin. Science 2003, 301, 1884-1886. Nanoscience enables ultrasensitive detection of Alzheimer's biomarker. Student: Xu Zhang. Alzheimer's disease.

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Nanoscience enables ultrasensitive detection of Alzheimer's biomarker

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  1. Christine D. Keating . PNAS 2005, 102, No. 7, 2263 –2264 Jwa-Min Nam, Shad Thaxton, Chad A. Mirkin. Science 2003, 301, 1884-1886 Nanoscience enables ultrasensitive detection of Alzheimer's biomarker Student: Xu Zhang

  2. Alzheimer's disease • Alzheimer's disease (AD), which afflicts an estimated 16 million people worldwide, is a neurodegenerative dementia characterized by memory loss and cognitive impairment. • Symptoms begin with mild cognitive impairment. • It’s tough to distinguish from other more benign forms of age-related dementia.

  3. Alzheimer's disease • Smaller, soluble oligomers of peptides, referred to as amyloid--derived diffusible ligands (ADDLs), have recently been hypothesized as the causative agent in AD-related memory loss. • Support for the role of ADDLs comes from their neurotoxicity, and mouse studies that indicate a reversal of memory loss upon injection of amyloid- antibodies • This paper presented an ultrasensitive, nanoparticle-based protein detection strategy termed bio-barcode amplification (BCA) to detect ADDL concentration in the cerebrospinal fluid (CSF).

  4. Bio-barcode Amplification (BCA) Strategy • CSF is first exposed to monoclonal anti-ADDL antibodies bound to magnetic microparticles. • After ADDL binding, the microparticles are separated with a magnetic field and washed before addition of secondary antibodies bound to DNA:Au nanoparticle conjugates. • Unreacted Au nanoparticle conjugates are removed after magnetic separation, then elevated temperature release the barcode DNA for analysis. • Each Au nanosphere carries hundreds of identical barcode DNA strands, providing substantial amplification.

  5. Scanometric DNA detection • The probe strands are arrayed on a solid support and the detection strand is bound to an Au nanosphere. • The selectively assembled Au nanospheres then act as nucleation sites for Ag deposition upon the chemical reduction of Ag+ from solution. • The resulting Ag deposits can be quantified by a simple desktop scanner such as is used to scan documents for computer manipulation (hence scanometric)

  6. Advantages • Ultrasentivity with built-in signal amplification mechanism. 30 attomolar (30 x 10-18 M) for protein targets, useful for early diagnosis. • Can also be applicable for DNA or RNA diagnosis, or simultaneously multiple monitoring. • Rapid diagnosis due to performing the BCA assay in homogeneous suspension. • It marks one of the first real applications of nanotechnology, while the vast majority of the countless publications on nanoparticle-based diagnostics are in the proof-of-principle stage.

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