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Electrochemical activation and monitoring of autocatalytic reactions for exponential signal amplification: towards the development of ultrasensitive bioanalytical assays.

ABG-91611 Sujet de Thèse
23/04/2020 < 25 K€ brut annuel
Université de Paris
Paris - Ile-de-France - France
Electrochemical activation and monitoring of autocatalytic reactions for exponential signal amplification: towards the development of ultrasensitive bioanalytical assays.
  • Chimie
  • Biotechnologie
  • Physique
Electrochemistry, Autocatalysis, Bioassays, Signal amplification

Description du sujet

The ongoing pandemic of Covid-19 spectacularly shed light on the importance of appropriate detection tools to help understanding the infection’ spread and propose strategic sanitary responses. Ideal detection policy must rely on a detection tool that has two major features: (1) it must be cheap and easy-to-use to ensure testing the majority of the population; (2) it must be sufficiently sensitive to detect very low viral load or early immune response in the case of serological assays. Obviously, there is still an urgent need to develop these types of ideal assays.

Practically, sensitive assays necessarily involve signal amplification strategies. Among the different signal amplification strategies, those based on an autocatalytic reaction are certainly, due to their exponential nature, among the most powerful approaches for improving the analytical performances of bioassays. This has been for instance illustrated with the immuno-PCR, a technique combining the signal amplification power of PCR (an autocatalytic reaction) with the specificity of an immunoassays.[1] Alternatives to DNA chemistry-based exponential amplification are very rare and most examples relies on the relatively slow dendritic chain reactions.[2] As a substitute approach, we have recently reported the proof-of-concept of a new autocatalytic molecular signal amplification, that we believed is quite promising for the development of ultrasensitive bioanalytical assays.[3]

Our new approach is simply based on a molecular chemical reaction network in which two catalytic loops are in a self-activation dependency, making it possible to amplify exponentially the concentration of each of the catalysts. Reaction progress may be followed spectroscopically but also electrochemically through the electrochemical signature of the RCC/naphthoquinone. In this PhD project, we will aim at demonstrating that electrochemical methods may be used not only as a read-out of the signal (electrochemical monitoring) but also as contributor to the autocatalytic process (electrochemically-induced amplification). For such a purpose, a specific design of the detection cell will be required along with the conception and preparation of new molecular probes. Such an electrochemical triggering and monitoring of an autocatalytic signal amplification process has never been described so far and thus represents a great challenge. The final objective of this PhD will be then to develop ultrasensitive assays of biomolecules.

 

[1]. (a) T. Sano, C.L. Smith, C.R. Cantor, Science, 1992, 258, 120-122 ; (b) M. Adler, R. Wacker, C. M. Niemeyer, Analyst 2008, 133, 702-718.

[2]. M. E. Roth, O. Green, S. Gnaim, D. Shabat, Chem. Rev., 2016, 116, 1309-1352.

[3]. J. Pallu, C. Rabin, G. Creste, M. Branca, F. Mavré, B. Limoges, Chem. Eur. J., 2019, 25, 7534-7546.

Nature du financement

Contrat doctoral

Précisions sur le financement

Présentation établissement et labo d'accueil

Université de Paris

The Laboratoire d’Electrochimie Moléculaire (LEM) is a joined research laboratory between Université de Paris and CNRS (UMR 7591). It is internationally recognized in the field of molecular electrochemistry, especially for its contribution to the general understanding of all aspects of electron transfer chemistry coupled to both molecular changes and/or dynamical electron transport within molecules and biomolecules, but also within redox-active materials and catalytic films deposited on electrodes surfaces.

The PhD candidate will be part of the team « MER » (Electroanalytical methodologies and reactivity). The expertise of the team is mainly the development and design of new bioelectroanalytical methodologies (bioaffinity electrodes, enzyme-based biosensors, aptasensors, and electrochemical methods for sensitive detection of nucleic acids).

Profil du candidat

Candidates should have theoretical and practical background in electrochemistry and/or analytical chemistry, and interests in molecular chemistry and biomolecular analysis.

Eligibility conditions:

- Candidates must hold a master degree (or equivalent diploma) before starting the PhD;

- Candidates should have no prior inscription in PhD.

Date limite de candidature

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