Elsevier

IRBM

Volume 35, Issue 2, April 2014, Pages 66-71
IRBM

ANR TECSAN 2010
Detection of urinary modified nucleosides by a bulk acoustic wave MIP sensor – Results and future work

https://doi.org/10.1016/j.irbm.2014.02.009Get rights and content

Abstract

This paper presents an overview of the main actions and projects of the ANR TECSAN “CancerSensor” during the 2011–2014 period. The project aims to develop and validate a quantitative, non-invasive therapeutic tool to detect selected urinary modified nucleosides as biomarkers of colorectal cancer chemotherapy and to monitor in fine the efficiency of the chemotherapy. A methodology has been developed to generate a bulk acoustic wave molecularly imprinted polymer sensor (SAW-MIP) for the detection of various nucleosides and nucleotides of interest. A rapid and sensitive mass spectrometry method has been also developed.

Introduction

Modified nucleosides, derived predominantly from transfer ribonucleic acid (tRNA), have been shown to be excreted in abnormal amounts in the urine of cancer patients. Around 20 of them have been already used as tumour markers for instance: for breast cancer [1], [2], for colon and liver cancer [3], for lung cancer [4]. Pseudouridine, 1-methyladenosine, 1-methylguanosine, 2-methylguanosine, 1-methylinosine, 2-pyridone-5-carboxamide-N1-ribofuranoside are some of the modified nucleosides (Fig. 1). These modified nucleosides cannot be reutilized or further degraded, but they are excreted in the urine as intact molecules because they do not have a salvage pathway [5]. The urinary excretion of such modified nucleosides is relatively low but it is an indication of the higher turnover rate of tRNA in tumour tissues [6].

Although different analytical techniques have been reported for the determination of urinary nucleoside levels, their detection is still challenging due to the low level of modified nucleosides but also to the complexity of urine (in a less intend, blood) biological matrix. Actual well-established analytical techniques (SPE-HPLC-UV, CE-UV, LC-MS/MS, GC-MS/MS) are restrictive. Thus, to develop and validate a quantitative, non-invasive diagnosis tool to monitor the efficacy of chemotherapy in patients with colorectal cancer, we have developed an acoustic-biosensor based on molecularly imprinted polymers (MIP). It includes advances which will take the sensitivity down to a low-concentration single-molecule level.

Section snippets

Results for the period 2011–2014

From 10 selected modified nucleosides mainly found in patients with histological diagnosed malignant tumours (colorectal cancers), we wish:

  • to develop an acoustic-sensor and reagent strips for a new simple, sensitive, non-invasive, cost-effective and real-time urinalysis of trace modified nucleosides tumour cancer;

  • to use molecularly imprinted polymer technology, which has demonstrated speed and selectivity, to fix it on the acoustic-sensor or on a reagent strips;

  • to use those tools to the

Future plans (work in progress)

In the next future, we will continue our activities on three directions:

  • the development of an acoustic wave MIP sensor for pseudouridine nucleoside, which is predominantly found in urine from cancer patients;

  • as the liquid chromatography-mass spectrometry methods for urinary biomarkers detection is now available, it will be applied for the analysis of urine samples collected from large cohorts of cancer patients;

  • apart from detecting and identifying tumour markers in the urine samples, the effect

Acknowledgement

The authors sincerely thank the National Research Agency (ANR-10-TECS-0004; http://www.agence-nationale-recherche.fr/) for financial support. The acoustic wave MIP sensor part of this project was in part granted by the Polytechnical Institute of Bordeaux (IPB). Monique Benoît and Veronique Conédéra (Technological Network RTB, LAAS, CNRS, Toulouse-France), for realizing acoustic wave delay lines, as well as Bernard Plano (IMS-Bordeaux) for SEM images.

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