Ligand-Capped Ultrapure Metal Nanoparticle Sensors for the Detection of Cutaneous Leishmaniasis Disease in Exhaled Breath

Abstract

Human cutaneous leishmaniasis, although designated as one of the most neglected tropical diseases, remains underestimated due to its misdiagnosis. The diagnosis is mainly based on the microscopic detection of amastigote forms, isolation of the parasite, or the detection of Leishmania DNA, in addition to its differential clinical characterization; these tools are not always available in routine daily practice, and they are expensive and time-consuming. Here, we present a simple-to-use, noninvasive approach for human cutaneous leishmaniasis diagnosis, which is based on the analysis of volatile organic compounds in exhaled breath with an array of specifically designed chemical gas sensors. The study was realized on a group of n = 28 volunteers diagnosed with human cutaneous leishmaniasis and a group of n = 32 healthy controls, recruited in various sites from Tunisia, an endemic country of the disease. The classification success rate of human cutaneous leishmaniasis patients achieved by our sensors test was 98.2% accuracy, 96.4% sensitivity, and 100% specificity. Remarkably, one of the sensors, based on CuNPs functionalized with 2mercaptobenzoxazole, yielded 100% accuracy, 100% sensitivity, and 100% specificity for human cutaneous leishmaniasis discrimination. While AuNPs have been the most extensively used in metal nanoparticle−ligand sensing films for breath sensing, our results demonstrate that chemical sensors based on ligand-capped CuNPs also hold great potential for breath volatile organic compounds detection. Additionally, the chemical analysis of the breath samples with gas chromatography coupled to mass spectrometry identified nine putative breath biomarkers for human cutaneous leishmaniasis.

Breath Analysis: A Promising Tool for Disease Diagnosis—The Role of Sensors

“…The most common types of hybrid sensing layers are those composed of a conductive inorganic material, surrounded by an organic functional film where the gaseous analytes are adsorbed therefore changing the conductivity of the device [ 15 ]. CNTs, MNPs (e.g., Au) [ 15 ], or carbon black [ 15 , 108 ] can be used as the conductive part while non-conducting molecular ligands (MCNPs) [ 51 , 108 , 109 ] or polymers [ 110 ] as the organic one. Such sensors offer the prospect of cross-reactive sensor-array development since the organic part is selected based on the chemical and physical properties of the VOCs [ 16 ].…”

Recent Advances in Nanomaterial‐Enabled Wearable Sensors: Material Synthesis, Sensor Design, and Personal Health Monitoring

“…[ 108 ] VOC analysis can be used in disease diagnoses, such as diabetes, [ 109 ] lung cancer, [ 5a,110 ] and human cutaneous leishmaniasis. [ 111 ] There are several methods in gas molecule detection, such as gas chromatography–mass spectrometer (GC–MS), [ 112 ] laser spectrometry, [ 113 ] and ion mobility spectrometry. [ 114 ] However, such methods require bulky instruments and complicated procedures, which are not suitable for real‐time and in situ detection.…”

“…Reproduced with permission. [ 8 ] Copyright 2018, American Chemical Society. c) graphene‐based wearable sensor for pathogenic bacteria detection.…”

Nanodiagnostics in leishmaniasis: A new frontiers for early elimination

“…Volatile organic compounds from the exhaled breath can act in this direction for noninvasive detection of several forms of leishmaniasis using metal NPs. Although this has been studied for CL by Welearegay et al (2018), their application to the other forms of leishmaniasis should be pushed for the desired outcome of early detection leading to early elimination.…”

“…Cutaneous leishmaniasis Not available (Welearegay et al, 2018) Abbreviations: Chr, chromosome; NP, nanoparticle; QD, quantum dots; ssDNA, single-stranded DNA; SSU, small subunit; VL: visceral leishmaniasis.…”