Graphene Oxide Based Recyclable in Vivo Device for Amperometric Monitoring of Interferon-γ in Inflammatory Mice

Abstract

Cytokine sensing is challenging due to their typically low abundances in physiological conditions. Nanomaterial fabricated interfaces demonstrated unique advantages in ultrasensitive sensing. Here, we demonstrate an amperometric sensing device based on graphene oxide (GO) and structure-switching aptamers for long-term detection of cytokines in a living organism. The device incorporates a single layer of GO acting as a signal amplifier on glassy carbon electrodes. The hairpin aptamers specific to interferon-γ (IFN-γ), which were loaded with redox probes, are covalently attached to GO to serve as biorecognition moieties. IFN-γ was able to trigger the configuration change of aptamers while releasing the trapped redox probes to introduce the electrochemical signal. This in vivo device was capable of quantitatively and dynamically detecting IFN-γ down to 1.3 pg mL secreted by immune cells in cell culture medium with no baseline drift even at a high concentration of other nonspecific proteins. The biocompatible devices were also implanted into subcutaneous tissue of enteritis mice, where they performed precise detection of IFN-γ over 48 h without using physical barriers or active drift correction algorithms. Moreover, the device could be reused even after multiple rounds of regeneration of the sensing interface.

Cytokines: From Clinical Significance to Quantification

“…In this regard, structure‐switching molecules have demonstrated their potential in real‐time detection of analytes. [ 26 ] A molecular beacon aptamer based biosensing device has been developed toward the near real‐time [ 36 ] and real‐time monitoring of IFN‐ γ . [ 121 ] Such a platform has been proven sensitive for the detection of cytokines in the pg mL −1 range.…”

Is carboxylation an efficient method for graphene oxide functionalization?

“…17,18 The high surface area of GO allows adsorption of a large amount of drugs, 6,19 RNA 20,21 or nanoparticles, 22 while bioactive molecules can also be covalently conjugated via the oxygenated groups. 23 The possibility of graing functionalities onto the surface of GO greatly extends its application to different areas. [24][25][26][27] Compared to noncovalent complexation, covalent functionalization enables us to prepare more stable conjugates and minimize the release of molecules adsorbed onto the GO surface, especially for biological applications.…”

Ultrasensitive Electrochemical DNA Biosensor Fabrication by Coupling an Integral Multifunctional Zirconia-Reduced Graphene Oxide-Thionine Nanocomposite and Exonuclease I-Assisted Cleavage

“…Then, a large amount of thionine molecules were adsorbed onto the rGO surface, via π-π stacking, as an excellent electrochemical probe. Graphene or graphene oxide-based two-dimensional materials have been widely explored for application in biosensor and biomedicine, owing to their fascinating electronic, thermal, mechanical, and chemical properties (Dong et al, 2012 ; Chen et al, 2016 ; Cao et al, 2018 ; Campos et al, 2019 ). The obtained ZrO 2 -rGO-Thi nanocomposite was used as an integral multifunctional sensing element for DNA recognition, signal amplification, and reporting.…”