A Flexible and Regenerative Aptameric Graphene–Nafion Biosensor for Cytokine Storm Biomarker Monitoring in Undiluted Biofluids toward Wearable Applications

Abstract

Wearable sensors that can conveniently detect cytokine levels in human biofluids are essential for assisting hospitals to maximize the benefits of anti‐inflammatory therapies and avoid cytokine storms. Measurement of cytokine levels in biofluids still remains challenging for existing sensors due to high interference from the background. Here, this challenge is overcome through developing a flexible and regenerative aptameric field‐effect transistor biosensor, consisting of a graphene–Nafion composite film, for detecting cytokine storm biomarkers in undiluted human biofluids. The composite film enables the minimization of nonspecific adsorption and empowers the renewability to the biosensor. With these capabilities, the device is capable of consistently and sensitively monitoring cytokines (e.g., IFN‐γ, an inflammatory and cancer biomarker) in undiluted human sweat with a detection range from 0.015 to 250 nm and limit of detection down to 740 fm. The biosensor is also shown to incur no visible mechanical damage and maintain a consistent sensing response throughout the regenerative (up to 80 cycles) and crumpling (up to 100 cycles) tests. Experimental results demonstrate that the biosensor is expected to offer opportunities for developing wearable biosensing systems for distinguishing acute infectious disease patients and monitoring of patients’ health conditions in daily life.

An Intelligent Graphene‐Based Biosensing Device for Cytokine Storm Syndrome Biomarkers Detection in Human Biofluids

“…On the basis of the fitted curve demonstrated in Figure 4b, saturated coefficient A, binding equilibrium constant K D and Hill coefficient m are estimated to be 1.254, 2.125 × 10 −9 m, and 0.288, respectively. According to the 3σ rule, [29] the limit of detection (LOD) for IFN-γ detection of the DGTFET biosensing device is calculated to be 476 × 10 −15 m, which is much lower than the LODs that obtained by previously reported IFN-γ sensors, [9,30] indicating the high sensitivity of our sensor. Then, the effect from extended-time storage on the consistency and reliability of our sensor is investigated.…”

“…Cytokine IL-6 was purchased from ACRO Biosystems (Newark, DE). Specific aptamers for IFN-γ (sequence 5'-NH 2 -GGG GTT GGT TGT GTT GGG TGT TGT GT -3'), [14] TNF-α (sequence 5'-NH 2 -TGG TGG ATG GCG CAG TCG GCG ACA A-3') [9,40] and IL-6 (sequence 5'-NH 2 -GGT GGC AGG AGG ACT ATT TAT TTG CTT TTC T-3') [41] were synthesized and purified by Sangong Biotech (Shanghai, China). Fetal calf serum was purchased from Tianhang (Zhejiang, China).…”

“…The capsule consists of an adhesive and disposable membrane which could be attached to the forehead, forearm or neck with a fluid-tight window giving access to collect sweat. [9] The collected sweat sample was stored at 2 °C before biomarker solution configurations. The experiments involving human subjects have been performed with the full, informed consent of the volunteers.…”

“…Due to the simple configuration, easy and economic fabrication process, high sensitivity and short response time, aptameric graphene-based field effect transistor (GFET) sensors have been reported for label-free and highly specific recognition of virus, ions, hormones, cells, DNA, glucose, and cytokines. [9][10][11][12][13][14] However, unwanted interferences generated from changes in environmental condition parameters (e.g., pH and ionic strength) and nonspecific adsorption of complex components in human biofluids always impact the GFET sensing performance and hamper its practical clinical applications. [15][16][17] In this work, we present an intelligent aptameric dual channel graphene-TWEEN 80 field effect transistor (DGTFET) Abnormal elevated levels of cytokines such as interferon (IFN), interleukin (IL), and tumor necrosis factor (TNF), are considered as one of the prognosis biomarkers for indicating the progression to severe or critical COVID-19.…”

Graphene nanocomposites for transdermal biosensing

“…Structures that contained layer‐by‐layer sandwiching of graphene with polymers showed appropriate capacitive pressure sensing functionality. Graphene‐polymer composites have also been used for electrochemical the detection of cortisol, glucose, and cytokines in sweat (Toi et al, 2019; Torrente‐Rodríguez et al, 2020; Wang et al, 2020). To date, however, there has been no comprehensive review on transdermal biosensing using graphene‐based nanocomposites.…”