Download Self-Assembly at nano-Scale Binary Nanoparticles Superlattices

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
•
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.
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 ADrelated 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).
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.
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)
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.