ARLINGTON, Va.Using their
novel bio-bar-code amplification (BCA) technology,
researchers analyzing fluid from around the brain
and spinal cord have detected a protein linked in
recent studies to Alzheimer's disease.
If proven successful in further
clinical studies, the procedure could become the first
tool for early diagnosis of Alzheimer's, and the first
test to conclusively identify the disease in living
Chad Mirkin and William Klein
of the National Science Foundation (NSF) Nanoscale
Science and Engineering Center (NSEC) for Nanopatterning
and Detection Technologies at Northwestern University,
and their colleagues, announce their findings the
week of Jan. 31 in the online edition of the Proceedings
of the National Academy of Sciences.
Because of the extreme sensitivity
of the BCA process that Mirkin's team developed, the
researchers were able to detect within each fluid
sample a miniscule amount of proteins called amyloid
ß-derived diffusible ligands (ADDLs). The goal
is to detect and validate infinitesimal amounts of
the biomarkers in blood.
Research by Klein and his colleagues
suggests that ADDLs first appear in the earliest stages
of Alzheimer's. If the BCA process can identify the
markers before symptoms develop, doctors may be able
to combat the illness in its nascent form when treatments
may be most effective.
In the first steps of the BCA
process, unique microparticles latch onto the biomarker
targets in this study, the ADDLs. The particles
are magnetic, a property that aids collection at the
end of the procedure. Researchers then add a second
ingredient that consists of a gold nanoparticle core
surrounded by hundreds of identical DNA strands, which
serve as hundreds of "bio-bar-codes" the
researchers can detect at the end of the test. Ultimately,
the gold-DNA particles and magnetic particles sandwich
the biomarker targets.
A magnet separates the sandwich
complexes from the rest of the sample. The complexes
are then heated to release the DNA bar codes, which
are then measured by an extremely sensitive detector.
Each DNA piece greatly increases the sensitivity of
the test and its potential to tell doctors a patient
carries the ADDLs.
According to the researchers,
BCA is about 1 million times more sensitive than the
next best thing standard enzyme-linked immunoassays
(ELISAs). ELISAs do not have the sensitivity required
to detect ADDLs in cerebrospinal fluid.
BCA could eventually be configured
to detect hundreds of diseases simultaneously with
a single procedure, doctors could quickly and inexpensively
test a blood sample for any number of ailments. The
researchers developed BCA to detect a mere few dozen
molecules amongst a sample filled with billions and
have already experimented with biomarkers for AIDS
and prostate cancer.
This research was supported
by both NSF's Engineering Research Centers program
and the NSF Office on International Science and Engineering.
Comments from the researchers:
"This study is a major
step forward in identifying a routine diagnostic tool
for Alzheimer's disease, and it validates our hypothesis
that there are many biomarkers for disease that go
under the radar of conventional diagnostic tools.
The extraordinary sensitivity of the bar code assay
has a chance to change the way the medical community
thinks about molecular diagnostics and the markers
they consider for many types of diseases."
Chad Mirkin, Northwestern University Department of
Chemistry and Institute for Nanotechnology
"It's a good bet that
the very earliest stage of AD memory loss begins when
ADDLs attack key synapses in the brain. We predicted
some of these ADDLs would leak into the cerebrospinal
fluid, but until now we couldn't detect them. Thanks
to the extraordinary sensitivity of the BCA it's been
possible to validate the prediction, and maybe even
set the stage for creating the first clinical lab
test for Alzheimer's disease. " -- William Klein,
Northwestern University Institute for Neuroscience
Comments from NSF:
"The researchers have
pioneered a promising new technology in the emerging
area of nanobioengineering. These nanoengineered particles
have the capability to effectively interface with
biological molecules." Sohi Rastegar, a bioengineering
expert and the NSF program director who oversees the
agency's support of the Northwestern NSEC and several
other bioengineering centers.
"This will be a biosensing
system with high sensitivity and specificity that
can help health professionals diagnose many debilitating
diseases. This is particularly important for diseases
like Alzheimer's where a reliable diagnostic tool
is lacking and early intervention could have a significant
impact on the lives of patients and their loved ones,
in addition to lowering health care costs."
Joshua A. Chamot, NSF (703) 292-8070 firstname.lastname@example.org
Sohi Rastegar, NSF (703) 292-5379 email@example.com
Chad Mirkin, Northwestern University (847) 467-7302
William Klein, Northwestern University (847) 491-5510
Chad Mirkin research page: http://www.chem.northwestern.edu/~mkngrp/
William Klein research page: http://www.northwestern.edu/nuin/faculty/Klein_W_L/
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