Abstract

Serotonin is an important neurotransmitter that plays a major role in the pathogenesis of a variety of conditions, including psychiatric disorders. The detection of serotonin typically relies on high-performance liquid chromatography (HPLC), an expensive technique that requires sophisticated equipment and trained personnel, and is not suitable for point-of-care applications. In this contribution, we introduce a novel sensor platform that can measure spiked neurotransmitter concentrations in whole blood samples in a fast and low-cost manner by combining synthetic receptors with a thermal readout technique—the heat-transfer method. In addition, the design of a miniaturized version of the sensing platform is presented that aims to bridge the gap between measurements in a laboratory setting and point-of-care measurements. This fully automated and integrated, user-friendly design features a capillary pumping unit that is compatible with point-of-care sampling techniques such as a blood lancet device (sample volume—between 50 µL and 300 µL). Sample pre-treatment is limited to the addition of an anti-coagulant. With this fully integrated setup, it is possible to successfully discriminate serotonin from a competitor neurotransmitter (histamine) in whole blood samples. This is the first demonstration of a point-of-care ready device based on synthetic receptors for the screening of neurotransmitters in complex matrices, illustrating the sensor’s potential application in clinical research and diagnosis of e.g., early stage depression.

Highlights

  • Mood disorders, in particular depression with a lifetime prevalence of 15–20%, are the most common form of psychiatric disorders in Europe [1,2]

  • Selectivity was analyzed by studying the response of a molecularly imprinted polymers (MIPs)-coated chip to an increasing concentration of an analogue neurotransmitter, the response of a MIP-coated chip to an increasing concentration of an analogue neurotransmitter, histamine

  • The dose-response curve indicates that there is not specific effect observed in both of the reference measurements, while significant increases in the thermal resistance observed in both of the reference measurements, while significant increases in the thermal resistance effect already become apparent at concentrations of ±400 nM for the MIP-coated samples after which effect already become apparent at concentrations of ±400 nM for the MIP-coated samples after which a stepwise increase can be observed spanning the higher nanomolar and low micromolar range

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Summary

Introduction

In particular depression with a lifetime prevalence of 15–20%, are the most common form of psychiatric disorders in Europe [1,2]. It is known that for many psychiatric disorders, neurotransmitters and their receptors play a major role in the pathogenesis [5,6]. The balance between the neurotransmitters dopamine and serotonin is of important significance when developing novel treatments or medications [7,8]. Serotonin cannot be transported across the blood-brain barrier, anomalous whole blood serotonin levels are correlated with clinical depression [9,10,11], and timely intervention in a personalized medicine-based setting can significantly reduce the associated medical and socio-economics burdens [12,13]. Serotonin is involved in steering numerous behavioral and physiological functions and abnormalities in serotonin levels are found in patients with e.g., hypertension [14] and gastrointestinal disorders such as irritable bowel syndrome (IBS) [15]

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