# Advances in Graphene Field Effect Transistors (FETs) for Annine Neurotransmitter Sensing
## 4 Challenges and Limitations
### Interference and Simultaneous Detection  
The primary challenge in point-of-care diagnostics biosensing applications lies in the effective detection of bioanalytes within unprocessed or minimally processed complex samples, including whole blood or cerebrospinal fluid. In these environments, biofouling and harsh conditions can disrupt bio-affinity layers, reducing their efficacy [263]. Biosensor performance is critical in dynamic assays with various interfering molecules, including proteins, lipids, and blood cells. Chemicals such as ascorbic acid and uric acid make it difficult to identify amine NTs because they produce overlapping signals or compete for binding sites on the sensor, resulting in false positives or inaccurate assessments of NT levels.  
While the single detection of amine NTs using GFETs is established, there are few examples of simultaneous detection. The issue stems from the NTs' similar molecular structures and electrochemical properties, making it difficult for GFET sensors to distinguish between them. Furthermore, selectively functionalising various NTs on the same graphene channel complicates tests because binding agents specific to one NT may not work for another. On bare electrodes, DA and SER have overlapping oxidation potentials, which causes problems with selectivity and repeatability [264].  
The simultaneous detection in complex matrices aims to improve analytical performance by capitalising on the synergistic effects of hybrid material components [26]. Emphasising synergistic effects can increase active surface area and electron transfer rates between the analyte and electrode surfaces while remaining biocompatible, which is critical for real-world applications. The covalent modification of rGO with a porphyrin derivative enables simultaneous DA and SER detection [265]. Functionalising GO and MWCNTs with RuO\({}_{2}\) nanowires, CeO\({}_{2}\) and Au nanofibers enables concurrent DA, SER, and ascorbic acid monitoring [266]. Electrografting two GFETs with carboxyl and amino radicals has demonstrated the potential for employing aptamer-functionalised multiplexed neural probes to monitor DA and SER release in vivo [163]. Electrostatic gating improves signal response by adjusting the V\({}_{\text{G}}\) to selectively detect a small concentration of target analytes. AgNPs have strong electrocatalytic capabilities towards DA, and the combination electron exchange properties of AgNPs and CNTs improve electrochemical reaction kinetics at the sensor surface [267, 268, 269, 270], leading to interference-free sensing platforms [271].  
Noise reduction strategies, including machine learning algorithms, can be used to eliminate interfering signals. A miniaturised electrochemical platform based on MWCNT for the simultaneous detection of DA and SER assessed the signal fit reliability and error values using machine learning regression techniques [272]. It showed the sensor's capacity to detect these NTs in diluted blood serum with a low LOD, improved stability, and repeatability, resulting in less than 5% change in peak current.