Toward point-of-care management of chronic respiratory conditions: Electrochemical sensing of nitrite content in exhaled breath condensate using reduced graphene oxide

Abstract

We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate (EBC). We discuss the fabrication and characterization of a miniaturized electrochemical sensor for detecting nitrite content in EBC using reduced graphene oxide. The nitrite content in EBC has been demonstrated to be a promising biomarker of inflammation in the respiratory tract, particularly in asthma. We utilized the unique properties of reduced graphene oxide (rGO); specifically, the material is resilient to corrosion while exhibiting rapid electron transfer with electrolytes, thus allowing for highly sensitive electrochemical detection with minimal fouling. Our rGO sensor was housed in an electrochemical cell fabricated from polydimethyl siloxane (PDMS), which was necessary to analyze small EBC sample volumes. The sensor is capable of detecting nitrite at a low over-potential of 0.7 V with respect to an Ag/AgCl reference electrode. We characterized the performance of the sensors using standard nitrite/buffer solutions, nitrite spiked into EBC, and clinical EBC samples. The sensor demonstrated a sensitivity of 0.21 μA μM − 1 cm − 2 in the range of 20-100 μM and of 0.1 μA μM − 1 cm − 2 in the range of 100-1000 μM nitrite concentration and exhibited a low detection limit of 830 nM in the EBC matrix. To benchmark our platform, we tested our sensors using seven pre-characterized clinical EBC samples with concentrations ranging between 0.14 and 6.5 μM. This enzyme-free and label-free method of detecting biomarkers in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory inflammation and disease.

High-sensitivity ion detection at low voltages with current-driven organic electrochemical transistors

“…Ions dissolved in aqueous media play a fundamental role in plants, animals, and humans. Ions regulate the biological processes at the single cell scale, enable the propagation of electronic signals and maintain a suitable balance between the fluids of the extracellular and intracellular environments, which is extremely important for several processes including nerve impulses, hydration, muscle function, and the regulation of pH level 1 – 7 . The in situ quantification of the ion concentration in aqueous media is thus gaining significant interest in several emerging fields including biomedical diagnostics, environmental monitoring, healthcare products, water and food test and control, agriculture industry and security 8 – 17 .…”

Structure, Properties, and Electrochemical Sensing Applications of Graphene‐Based Materials

“…Taniselass et al [134] focused on the applications of graphenebased (bio)sensors in medicine, not only for detecting cancer cells but also for monitoring non-communicable diseases (NCDs). The authors highlighted many studies on GO-or rGObased devices for detecting different markers for cardiovascular problems, [176] lung cancer, [177] asthma, [178] and diabetes [179] and revealed that the combination and functionalization of GO and rGO could result in versatile, sensitive, and specific devices for monitoring NCDs. Recently, Hu et al [180] described a highly sensitive sensor for quantifying α-synuclein, a protein that mutates or is present at high levels in Parkinson's disease (PD) patients.…”

A Study on Technology Competition of Graphene Biomedical Technology Based on Patent Analysis

“…There's an urgent need for improved, minimally invasive methods for the diagnosis and monitoring of respiratory diseases. For example, the scientists in Rutgers University-New Brunswick have created a graphene-based sensor that could lead to the earlier detection of looming asthma attacks and improve the diagnosis of asthma and other respiratory diseases, preventing hospitalizations and deaths [66]. It is followed by E05-U05C (Nanofilm), A12-V01 (Medicines, pharmaceuticals), B05-C06 (Elemental C or S), and D05-H09 (Testing and detection (Except Bacteria, Fungi, Viruses)).…”