Ultrasensitive Electrochemical Detection of Amyloid‑β Peptide Using a Homochiral Metal–Organic Framework Binding to the l‑Diphenylalanine Targeting Site

The high sensitivity and accuracy of amyloid-β
peptide (Aβ)
detection could provide strong support for early diagnosis, monitoring
of disease progression, and effective treatment of Alzheimer’s
disease (AD). Improving the specificity and affinity of sensing materials
for Aβ is key to detecting Aβ. Herein, an electrochemical
sensor based on an unmodified homochiral MOF, Zn-BPIleBp, was developed for the first time for the detection of Aβ1–40,
with an ultralow detection limit of 1.7 pM (7.36 pg/mL). The Zn-BPIleBp sensor also displays high-efficiency enantioselectivity
and ultrasensitivity in identifying diphenylalanine (PhePhe) corresponding
to the core recognition motif of Aβ1–40, with a high
peak current ratio (IL/ID) of 2.78, large potential difference (EL – ED) of 140 mV,
and ultralow detection limit of 34 fM for l-PhePhe. The sensor
has been successfully applied for the ultrasensitive quantification
of l-PhePhe and Aβ1–40 in racemic mixtures,
artificial cerebrospinal fluid (aCSF) and fetal bovine serum (FBS).
According to structural and spectral analysis, the high sensitivity
and affinity of homochiral MOF toward Aβ1–40, without
the involvement of any biomolecular modifications such as antibodies
or aptamers, stem from the structural, hydrophobic, and chiral matching
between the framework and Aβ1–40. This sensor proffers
a fast, highly stable, reproducible, ultrasensitive, and accurate
detection method for Aβ1–40, demonstrating great potential
in the clinical application of AD. This work also opens up new perspectives
for designing sensing platforms using MOFs as sensing materials and
expanding their functionality and applications to the fields of biological
and medical analysis.