TY - JOUR
T1 - Detection of multiplex exosomal miRNAs for clinically accurate diagnosis of Alzheimer's disease using label-free plasmonic biosensor based on DNA-Assembled advanced plasmonic architecture
AU - Song, Sojin
AU - Lee, Jong Uk
AU - Jeon, Myeong Jin
AU - Kim, Soohyun
AU - Sim, Sang Jun
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Alzheimer's disease (AD), the most common neurologic disorder, is characterized by progressive cognitive impairment. However, the low clinical significance of the currently used core AD biomarkers amyloid-beta and tau proteins remains a challenge. Recently, exosomes, found in human biological fluids, are gaining increasing attention because of their clinical significance in diagnosing of various diseases. In particular, blood-derived exosomal miRNAs are not only stable but also provide information regarding the different characteristics according to AD progression. However, quantitative and qualitative detection is difficult due to their characteristics, such as small size, low abundance, and high homology. Here, we present a DNA-assembled advanced plasmonic architecture (DAPA)-based plasmonic biosensor to accurately detect exosomal miRNAs in human serum. The designed nanoarchitecture possesses two narrow nanogaps that induce plasmon coupling; this significantly enhances its optical energy density, resulting in a 1.66-fold higher refractive-index (RI) sensitivity than nanorods at localized surface plasmon resonance (LSPR). Thus, the proposed biosensor is ultrasensitive and capable of selective single-nucleotide detection of exosomal miRNAs at the attomolar level. Furthermore, it identified AD patients from healthy controls by measuring the levels of exosomal miRNA-125b, miRNA-15a, and miRNA-361 in clinical serum samples. In particular, the combination of exosomal miRNA-125b and miRNA-361 showed the best diagnostic performance with a sensitivity of 91.67%, selectivity of 95.00%, and accuracy of 99.52%. These results demonstrate that our sensor can be clinically applied for AD diagnosis and has great potential to revolutionize the field of dementia research and treatment in the future.
AB - Alzheimer's disease (AD), the most common neurologic disorder, is characterized by progressive cognitive impairment. However, the low clinical significance of the currently used core AD biomarkers amyloid-beta and tau proteins remains a challenge. Recently, exosomes, found in human biological fluids, are gaining increasing attention because of their clinical significance in diagnosing of various diseases. In particular, blood-derived exosomal miRNAs are not only stable but also provide information regarding the different characteristics according to AD progression. However, quantitative and qualitative detection is difficult due to their characteristics, such as small size, low abundance, and high homology. Here, we present a DNA-assembled advanced plasmonic architecture (DAPA)-based plasmonic biosensor to accurately detect exosomal miRNAs in human serum. The designed nanoarchitecture possesses two narrow nanogaps that induce plasmon coupling; this significantly enhances its optical energy density, resulting in a 1.66-fold higher refractive-index (RI) sensitivity than nanorods at localized surface plasmon resonance (LSPR). Thus, the proposed biosensor is ultrasensitive and capable of selective single-nucleotide detection of exosomal miRNAs at the attomolar level. Furthermore, it identified AD patients from healthy controls by measuring the levels of exosomal miRNA-125b, miRNA-15a, and miRNA-361 in clinical serum samples. In particular, the combination of exosomal miRNA-125b and miRNA-361 showed the best diagnostic performance with a sensitivity of 91.67%, selectivity of 95.00%, and accuracy of 99.52%. These results demonstrate that our sensor can be clinically applied for AD diagnosis and has great potential to revolutionize the field of dementia research and treatment in the future.
KW - Alzheimer's disease (AD)
KW - Exosomal miRNAs (exo-miRs)
KW - Gold nanoparticles (AuNPs)
KW - Plasmonic biosensors
KW - Rayleigh scattering
UR - http://www.scopus.com/inward/record.url?scp=85120805051&partnerID=8YFLogxK
U2 - 10.1016/j.bios.2021.113864
DO - 10.1016/j.bios.2021.113864
M3 - Article
C2 - 34890883
AN - SCOPUS:85120805051
SN - 0956-5663
VL - 199
JO - Biosensors and Bioelectronics
JF - Biosensors and Bioelectronics
M1 - 113864
ER -