Abstract
Early diagnosis of Alzheimer’s disease (AD) is critical for preventing disease progression, however, the diagnosis of AD remains challenging for most patients due to limitations of current sensing technologies. A common pathological feature found in AD-affected brains is the accumulation of Amyloid-β (Aβ) polypeptides, which lead to neurofibrillary tangles and neuroinflammatory plaques. Here, we developed a portable ultrasensitive FET biosensor chip based on a self-assembled nanoporous membrane for ultrasensitive detection of Aβ protein in complex environments. The microscale semiconductor channel was covered with a self-assembled organic nanoporous membrane modified by antibody molecules to pick up and amplify the Aβ protein signal. The nanoporous structure helps protect the sensitive channel from non-target proteins and improves its stability since no chemical functionalization process involved, largely reduces background noise of the sensing platform. When a bio-gated target is captured, the doping state of the polymer bulk could be tuned and amplified the strength of the weak signal, achieving ultrasensitive detecting performance (enabling the device to detect target protein less than 1 fg/ml in 1 µl sample). Moreover, the device simplifies the circuit connection by integrating all the connections on a 2 cm × 2 cm chip, avoiding expensive and complex manufacturing processes, and makes it usable for portable prognosis. We believe that this ultrasensitive, portable, low-cost Aβ sensor chip shows the great potential in the early diagnosis of AD and large-scale population screening applications.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
M.C.J.A. Barber, Bonding in some Donor-Acceptor Complexes involving Boron Trifluoride.[J]. J. Chem. Soc. Faraday Trans. 2, 69 (1973)
L.C. Brazaca, J.R. Moreto, A. Martín et al., Colorimetric paper-based Immunosensor for simultaneous determination of Fetuin B and Clusterin toward Early Alzheimer’s Diagnosis[J]. ACS Nano. 13(11), 13325–13332 (2019)
P. Carneiro, S. Morais, M.C. Pereira, Nanomaterials towards Biosensing of Alzheimer’s Disease Biomarkers[J]. Nanomaterials, 2019, 9(12)
X. Chen, H. Pu, Z. Fu et al., Real-time and selective detection of nitrates in water using graphene-based field-effect transistor sensors[J]. Environ. Science: Nano. 5(8), 1990–1999 (2018)
C. L M. Current status of graphene transistors[J]. Solid State Phenom., 2010, 156: 499–509
G. Fisichella, S. Lo Verso, Di S. Marco et al., Advances in the fabrication of graphene transistors on flexible substrates[J]. Beilstein J. Nanotechnol. 8, 467–474 (2017)
F. Ghasemi, M.R. Hormozi-Nezhad, M. Mahmoudi, Label-free detection of β-amyloid peptides (Aβ40 and Aβ42): a colorimetric sensor array for plasma monitoring of Alzheimer’s disease[J]. Nanoscale. 10(14), 6361–6368 (2018)
F. Hui, S. Chen, X. Liang et al., Graphene Coat. Nanoprobes: Review[J] Cryst., 2017, 7(9)
N.J.B. Kamathewatta, T.M. Nguyen, R. Lietz et al., Probing selective self-assembly of Putrescine oxidase with controlled orientation using a genetically Engineered peptide Tag[J]. Langmuir. 37(24), 7536–7547 (2021)
K. Kim, M.J. Kim, D.W. Kim et al., Clinically accurate diagnosis of Alzheimer’s disease via multiplexed sensing of core biomarkers in human plasma[J]. Nat. Commun. 11(1), 119 (2020)
A. Koklu, S. Wustoni, V.E. Musteata et al., Microfluidic Integrated Organic Electrochemical transistor with a Nanoporous membrane for Amyloid-β Detection[J]. ACS Nano. 15(5), 8130–8141 (2021)
L B T, An XPS study of Si as it occurs in adsorbents, catalysts, and thin films.[J]. Appl. Surf. Sci. 15(1–4), 1–35 (1983)
P. Lin, F. Yan, Organic thin-film transistors for chemical and biological sensing[J]. Adv. Mater. 24(1), 34–51 (2012)
P. Madhavan, P.Y. Hong, R. Sougrat et al., Silver-enhanced block copolymer membranes with biocidal activity[J]. ACS Appl. Mater. Interfaces. 6(21), 18497–18501 (2014)
L.F. Mao, Finite size effects on the gate leakage current in graphene nanoribbon field-effect transistors[J]. Nanotechnology. 20(27), 275203 (2009)
A. Nabers, L. Perna, J. Lange et al., Amyloid blood biomarker detects Alzheimer’s disease[J]. EMBO Mol. Med., 2018, 10(5)
A. Nakamura, N. Kaneko, V.L. Villemagne et al., High performance plasma amyloid-β biomarkers for Alzheimer’s disease[J]. Nature. 554(7691), 249–254 (2018)
S.P. Nunes, R. Sougrat, B. Hooghan et al., Ultraporous Films with Uniform Nanochannels by Block Copolymer Micelles Assembly[J]. Macromolecules. 43(19), 8079–8085 (2010)
J.C. Park, S.H. Han, D. Yi et al., Plasma tau/amyloid-beta1-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease[J]. Brain. 142(3), 771–786 (2019)
D. Park, J.H. Kim, H.J. Kim et al., Multiplexed femtomolar detection of Alzheimer’s disease biomarkers in biofluids using a reduced graphene oxide field-effect transistor[J]. Biosens. Bioelectron. 167, 112505 (2020)
B. Peng, K. Cao, A.H.Y. Lau et al., Crystallized monolayer Semiconductor for Ohmic Contact Resistance, High Intrinsic Gain, and High Current Density[J]. Adv. Mater. 32(34), e2002281 (2020)
F. Schwierz, Graphene transistors[J]. Nat. Nanotechnol. 5(7), 487–496 (2010)
F. Song, A. Poljak, M. Valenzuela et al., Meta-analysis of plasma Amyloid-β levels in Alzheimer’s Disease[J]. J. Alzheimers Dis. 26, 365–375 (2011)
C. Toyos-Rodríguez, F.J. García-Alonso, De La A. Escosura-Muñiz, Electrochemical Biosensors Based on Nanomaterials for Early Detection of Alzheimer’s Disease[J]. Sensors 2020, 20(17)
S. Wang, M.Z. Hossain, K. Shinozuka et al., Graphene field-effect transistor biosensor for detection of biotin with ultrahigh sensitivity and specificity[J]. Biosens. Bioelectron. 165, 112363 (2020)
L. Xie, M. Liao, S. Wang et al., Graphene-Contacted Ultrashort Channel monolayer MoS(2) Transistors[J]. Adv. Mater., 2017, 29(37)
C. Yu, H. Liu, W. Ni et al., Theoretical study of the source-drain current and gate leakage current to understand the graphene field-effect transistors[J]. Phys. Chem. Chem. Phys. 13(8), 3461–3467 (2011)
Acknowledgements
This work was supported by the National Natural Science Foundation of China (Grant number: 32101160), Shenzhen Science and Technology Program (Grant number: GXWD20200830123048001, JCYJ20220530145600001), Foundation of Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument (Grant number: 2020B1212060077). We thank all authors for their contributions: Xiaona Cao and Xiaoping Hu contributed to device design, fabrication and characterization; Dr. Jin Huawei and Dr. Yu Zhenhua provided clinical support for the project; all other authors helped with detailed experiments and data collection. Competing interests: The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Contributions
Xiaona Cao and Xiaoping Hu contributed to device design, fabrication and characterization; Dr. Jin Huawei and Dr. Yu Zhenhua provided clinical support for the project; all other authors helped with detailed experiments and data collection.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Xiaona Cao and Xiaoping Hu contributed equally to this work.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Cao, X., Hu, X., Qiu, Z. et al. Ultrasensitive FET biosensor chip based on self-assembled organic nanoporous membrane for femtomolar detection of Amyloid-β. Biomed Microdevices 25, 25 (2023). https://doi.org/10.1007/s10544-023-00667-x
Accepted:
Published:
DOI: https://doi.org/10.1007/s10544-023-00667-x