Nano-Brush
Structure for Rapid Label-Free Differentiation of Alzheimer’s
Disease Stages and Direct Capture of Neuron-Derived Exosomes from
Human Blood Plasma
posted on 2023-11-24, 00:55authored byShu-Ping Lin, Wei-Ju Lee, Man-Cheng Sun, Yu-Hsiu Yang, Lester Uy Vinzons, Yi-Mei Lin, Yu-Ting Wei
The
measurement of the neurofilament light chain (NFL) in human
blood plasma/serum is a promising liquid biopsy for Alzheimer’s
disease (AD) diagnosis, offering advantages over conventional neuroimaging
techniques recommended in clinical guidelines. Here, a controllable
nano-brush structure comprising upstanding silicon nanowires coated
with indium tin oxide was employed as the sensing substrate. This
nano-brush structure was modified with an NFL antibody (NFLAb) via
silane coupling and then further connected as the extended gate in
a field-effect transistor (EGFET). Notable signal differences emerged
within a 2 min timeframe, enabling the label-free differentiation
in human blood plasmas among four distinct cohorts: healthy controls,
subjective cognitive decline, mild cognitive impairment, and dementia
due to AD. Our study indicates that achieving a surface roughness
exceeding 400 nm on the modified nano-brush structure enables the
effective electrical sensing in our EGFETs. These distinct electrical
responses measured via the NFLAb-modified nano-brush EGFETs can be
attributed to the combined effects of the captured NFLs and NFL-specific
neuron-derived exosomes (NDEs) found in dementia patients, as confirmed
by electron spectroscopy for chemical analysis, atomic force microscopy,
and scanning electron microscopy. Finally, the potential of quantitatively
detecting NDEs on the NFLAb-modified nano-brush structure was demonstrated
using spiked solutions containing NFL-specific NDEs from IMR-32 neuroblast
cells, wherein concentration-dependent changes were observed in the
EGFETs output signal. Our findings show that the NFLAb-modified nano-brush
EGFET enables rapid, label-free differentiation between healthy individuals
and patients at varying stages of AD.