br Methods br Transparency document br Introduction

Methods
Transparency document
Introduction Epinephrine (EP) is a critical hormone and catecholamine neurotransmitter in nervous system of mammals.1, 2, 3 It has been known to accelerate and regulate heartbeat, blood pressure, bronchodilation, mydriasis, blood sugar and lipolysis, and can hence be used in the treatment of different conditions like cardiac arrest, anaphylaxis, hypertension, bronchial asthma, etc.4, 5 High levels of epinephrine can lead to phaeochromocytoma, hypoglycaemia, myocardial infarction, while at low levels it leads to Parkinson's disease.6, 7 Nerve cells transmit signals to the other cells using a neurotransmitter like ecopipam (ACh), which was first discovered in the central nervous system. Acetylcholine (ACh) plays a key role in the activity of the nervous system in terms of behaviors, emotional responses, learning, and memory.8, 9 Acetylcholine is synthesized and regulated through a mechanism involving choline acetyl transferase, choline transporter and the vesicular acetylcholine transporter (VAChT) and once it is formed in the presynaptic neuron, it is stored for exocytotic release by vesicular acetylcholine transporter,10, 11 which is a SLC18 vesicular neurotransmitter. Vesicular acetylcholine is expressed in cholinergic cells of the central nervous system of mammals, including the basal forebrain and striatum, and also peripherally at neuromuscular junctions. Irregularity in the levels of acetylcholine has been observed in the case of Parkinson's and Alzheimer's diseases, progressive dementia, Schizophrenia, motor dysfunction, etc,14, 15, 16 and Alzheimer's disease, is considered to be due to the synthesis of lower levels of acetylcholine. Acetylcholine and epinephrine also alter the cardiac function by changing the ion fluxes and electric potential disturbances across cell membranes. Based on these above mentioned, the simultaneous determination of these compounds is a critical task. Different methods like high-performance liquid chromatography (HPLC)19, 20, 21 and electrochemical methods have been used to this end.22, 23 Specifically speaking, electrochemical techniques are mainly based on analyzing the relationship between the determine and current, voltage or resistance. The emergence of new materials, makes it possible to build new electrochemical sensors with enhanced sensitivity and stability, which offer advantages like fast response, good portability, ease of operation, low cost and higher accuracy and low detection limit, as compared with the HPLC-based techniques.25, 26, 27, 28, 29, 30 The properties of nanomaterials, on the other hand, are very well known to be influenced by their size and architecture, especially due to their surface rather than the nature of the bulk atoms. The very high surface/volume ratios in nanomaterials provide them with advantages such as fast reaction kinetics and makes them proper candidates for single-molecule detections. There has recently been an increasing level of interest on evaluating the physical, chemical and electronic properties of nano-materials for catalytic or sensor applications.32, 33 These materials have been used to modify electrode materials in terms of their electrochemical performance, and the modified electrodes have proven to offer various interesting advantages in bioscience.34, 35 The presence of nanoparticles enhances the surface area of the electrode materials and facilitates electron transfer and hence reaction rates. Screen printed electrodes (SPEs) were first introduced in the 1990s, and have been known to offer improved reliability, reproducibility, low cost and the possibility for mass-production. These electrodes are ductile devices which can be used in different forms, can be made of various materials, and can be easily modified using different biological species like enzymes, antibodies, synthetic recognition elements, etc.37, 38, 39, 40, 41 Direct electrochemical oxidation of epinephrine and acetylcholine using unmodified electrode has been found to create high overpotentials, which in turn increases the background currents, greatly limiting the detection limits. Thus, lanthanides-based materials modified electrodes developed for simultaneous determination of acetylcholine and epinephrine.