Abstract

Cancer is a leading cause of death worldwide and actual analytical techniques are restrictive in detecting it. Thus, there is still a challenge, as well as a need, for the development of quantitative non-invasive tools for the diagnosis of cancers and the follow-up care of patients. We introduce first the overall interest of electronic nose or tongue for such application of microsensors arrays with data processing in complex media, either gas (e.g., Volatile Organic Compounds or VOCs as biomarkers in breath) or liquid (e.g., modified nucleosides as urinary biomarkers). Then this is illustrated with a versatile acoustic wave transducer, functionalized with molecularly-imprinted polymers (MIP) synthesized for adenosine-5′-monophosphate (AMP) as a model for nucleosides. The device including the thin film coating is described, then static measurements with scanning electron microscopy (SEM) and electrical characterization after each step of the sensitive MIP process (deposit, removal of AMP template, capture of AMP target) demonstrate the thin film functionality. Dynamic measurements with a microfluidic setup and four targets are presented afterwards. They show a sensitivity of 5 Hz·ppm−1 of the non-optimized microsensor for AMP detection, with a specificity of three times compared to PMPA, and almost nil sensitivity to 3′AMP and CMP, in accordance with previously published results on bulk MIP.

Highlights

  • During the recent past, health and life expectancy of people all over the world have become major public concerns, involving obvious links with both diseases detection and treatment, as well as environmental quality as a causal link, among others [1,2]

  • Many sensing technologies are investigated for volatile organic compounds (VOCs) detection or monitoring, based on electrochemical methods (amperometric, potentiometric, based on field effect transistors (FET) or on chemiresistive material deposited on interdigitated electrodes (IDEs)), direct or indirect optical methods (including infrared (IR), Fourier transform infrared (FTIR), non-dispersive infrared (NDIR), diode laser sensing and ultraviolet (UV) absorption, surface plasmon resonance (SPR)), or using mechanical effect, such as microcantilever or piezoelectric transducer (quartz crystal microbalance (QCM), surface acoustic wave (SAW))

  • Of all acoustic wave devices, guided shear horizontal surface acoustic wave (SH-surface acoustic waves (SAW)) or Love wave (LW) devices appear most promising for biochemical detection in liquid environments: (1) SH-SAW are more sensitive than bulk waves to perturbations produced from the environment without the excessive loss associated with Rayleigh SAW in liquids; (2) the selected piezoelectric materials and transducer designs lead to high Q structures; (3) device frequencies can be scaled to high frequencies of hundreds of megahertz, enabling high sensitivity under conditions of noise reduction; and (4) devices are small, robust, and easy to incorporate into online low-cost systems [62]

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Summary

Introduction

Health and life expectancy of people all over the world have become major public concerns, involving obvious links with both diseases detection and treatment, as well as environmental quality as a causal link, among others [1,2]. Conventional analytical techniques, such as SPE-HPLC-UV, CE-UV, LC-MS/MS, GC-MS/MS, though offering convenient ways of analyzing complex real samples, they present some drawbacks and limitations These methods are not amenable to a rapid and routine clinical assay owing to the polar nature of nucleosides and nucleotides and inevitable complex sample pretreatment (extraction, deproteinization, derivatization, etc.) before analysis. There is still a crying need for the development of efficient tools in order to pre-empt this alarming problem that threatens public health In this context, microsensors are expected to offer complementary analytical tools compared to conventional methods, as devices dedicated to specific targets, with short response time and convenience of usage. These results are discussed in the perspective of future use, as diagnosis tool and more than that, as a tool for therapeutic drug monitoring (TDM)

Gas Media
Liquid Media
Love Wave Transducer
Molecularly-Imprinted Polymeric Thin Film
Buffer and Analog Nucleotides Solutions
Static and Dynamic Modes of Measurements
Microfluidic
AMP-MIP Thin Film Coating
Real Time Measurements
Detection of AMP
Specificity
Binding
Results Analysis and Comparison with the State-of-the-Art
Future Use for Patient-Tailored Chronomodulated Therapy
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