Lipid-Modified Graphene-Transistor Biosensor for Monitoring Amyloid-β Aggregation

Abstract

A graphene field-effect transistor (G-FET) with the spacious planar graphene surface can provide a large-area interface with cell membranes to serve as a platform for the study of cell membrane-related protein interactions. In this study, a G-FET device paved with a supported lipid bilayer (referred to as SLB/G-FET) was first used to monitor the catalytic hydrolysis of the SLB by phospholipase D. With excellent detection sensitivity, this G-FET was also modified with a ganglioside G-enriched SLB (G-SLB/G-FET) to detect cholera toxin B. Finally, the GM1-SLB/G-FET was employed to monitor amyloid-beta 40 (Aβ40) aggregation. In the early nucleation stage of Aβ40 aggregation, while no fluorescence was detectable with traditional thioflavin T (ThT) assay, the prominent electrical signals probed by G-SLB/G-FET demonstrate that the G-FET detection is more sensitive than the ThT assay. The comprehensive kinetic information during the Aβ40 aggregation could be collected with a G-SLB/G-FET, especially covering the kinetics involved in the early stage of Aβ40 aggregation. These experimental results suggest that SLB/G-FETs hold great potential as a powerful biomimetic sensor for versatile investigations of membrane-related protein functions and interaction kinetics.

Ionic contrast across a lipid membrane for Debye length extension: towards an ultimate bioelectronic transducer

“… Refs. ○ Si Av, S.Av, N.Av 100 pM 1× (100 mM) PBS Our work ○ CNT S.Av 2.5 μM 10 mM PBS 46 ○ CNT S.Av 5 μM 1 μM PBS 47 ○ OSC S.Av 10 nM 10 mM PBS 48 ○ Graphene Magainin 2 100 pM 10 mM NaF 27 ○ Graphene CTxB 12.5 nM 10 mM HEPES 49 × Si PSA 75 fg mL −1 1 mM PBS, 2 mM KCl 50 × Si Thrombin 330 pM Acetate buffer 51 × Si PSA 150 fM 100 μM PBS, 100 μM KCl 52 × Si cTnT 1 fg mL −1 100 μM PBS 53 × Si PSA 1 pg mL −1 1 μM PBS, 2 μM KCl 54 LOD limit of detection, Av Avidin, S.Av Streptavidin, N.Av NeutrAvidin, OSC organic semiconductor, PSA Prostate-specific antigen, cTnT Cardiac troponin T.

Fig. 5 Improved molecular detection via asymmetric ionic environment across the SLB.

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Potential of Microfluidics and Lab-on-Chip Platforms to Improve Understanding of “prion-like” Protein Assembly and Behavior

“…These methods have evolved and have been adapted for the reliable detection of the presence and aggregative stage of various amyloids (i.e., Orru et al, 2017;Saijo et al, 2019) in different biological samples (i.e., Fairfoul et al, 2016;Haley et al, 2016;Bongianni et al, 2017). In parallel to these biochemical methods, other engineering laboratories have developed ultrasensitive methods based on graphene oxide and entropy-driven strand displacement reaction (ESDR) with LOD of 20 pM (Zhou et al, 2018), or graphene field-effect transistor (G-FET) for β-amyloid formation (Kuo et al, 2018). Unfortunately, these methods are not currently used in patient-derived studies.…”

Improving the Sensory Properties of Layered Phospholipid-Graphene Films Due to the Curvature of Graphene Layers

“…The use of graphene-phospholipid complex is very promising in a wide range of biological applications [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. For example, phospholipid molecules coating graphene can enhance the antibacterial effect of laser-induced graphene [ 19 ].…”

“…One of the most promising areas of application of graphene–lipid structures is biosensorics. Various biosensor devices have been developed based on lipid-modified graphene [ 26 , 27 , 28 ]. The urgent task in the framework of the development of this field is to improve the sensitivity and stability of the lipid/graphene system-based sensors.…”