Covalent Bioelectrochemical Architectures for Continuous In Vivo Monitoring of NOx Species (M/F)

Job Description

Thesis Subject

We are seeking a PhD candidate for a three-year doctoral project based primarily at the Department of Molecular Chemistry (DCM), CNRS-Université Grenoble Alpes, under the direct supervision of Dr Andrew J. GROSS, with Dr Alan LE GOFF as co-supervisor.

This project lies within the field of electrochemical biosensor technologies for health. It focuses on the design of original enzyme-electrode interfaces and their integration into in vivo monitoring platforms. The project will contribute to two of the six CNRS transversal challenges for 2024-2028: The Brain and Materials of the Future, with the aim of improving our understanding of brain function and contributing to the development of new therapeutic strategies.

The aim of the project is to develop a new electrochemical multisensor platform for the continuous monitoring of NOx species (e.g. nitrate, nitrite and nitric oxide (NO)) in the living brain. Within the broader project, this platform will enable direct in vivo monitoring to provide a dynamic understanding of the NOx pathway and its relation to other biological pathways under normal and brain injury conditions. The sensors will help proveinsight into the beneficial and toxic effects related to dietary supplementation and help contribute towards the development of new therapeutic approaches.

Objectives:
• Engineer robust bioelectrode architectures via covalent assembly and efficient electrical wiring of reductases, providing new insight into electron-transfer and enzyme inhibition.
• Evaluate and enhance the selectivity, stability and biocompatibility of the bioelectrodes.
• Translate these architectures into implantable microelectrode biosensors.
• Validate the sensors in artificial media and rat models, including the generation of new in vivo data on NOx brain monitoring.

Additional biological objectives of the broader project:
• Characterise the physiological recruitment of NOx pathways.
• Determine if/how NO can be produced and modulated during brain injury.
This multidisciplinary project requires an interest in, and a strong background in, physical chemistry, particularly electrochemistry and analytical chemistry. A strong interest in or knowledge of biochemistry, especially enzymes and/or nitric oxide biology, would be highly desirable. This is an ambitious and exploratory project with a strong fundamental research component, contributing towards the development of future medical devices.

Your Work Environment

2. CONTEXT
Enzyme-modified electrochemical biosensors have transformed healthcare by enabling the rapid and accurate measurement of glucose and lactate in blood and ISF. Current wearable continuous glucose monitoring (CGM) systems now permit continuous, real-time glucose monitoring for 7-15 days.[1] These biosensors combine the excellent specificity of enzymes with the sensitivity, speed and portability of electrochemical detection. Extending the success of CGM to new biomarkers remains challenging, primarily due to limited enzyme and enzyme-electrode stability, inefficient wiring of enzyme active sites, and complications associated with interferences and biofouling. Furthermore, conventional biosensors rely on petroleum-derived polymers and toxic crosslinker chemistries, raising ecological concerns.

Recent advances by Dr Gross within the BioSEN team include UV-crosslinked hydrogel coatings and microneedles for CGM [2-3] Dextran-based microneedle biosensors enabled selective glucose monitoring for up to 10 d in an in-vitro skin model. Hydrogel-coated biosensors also enabled multi-day measurements in complex artificial interstitial fluid, with performance tuneable through methacrylation and crosslinking density. These covalently crosslinked gels therefore represent a promising strategy for long-term in vivo and in vitro biomarker monitoring. Electrografting of diazonium salts offers another route for constructing covalent bioelectrode architectures, as demonstrated by Dr Gross and Dr Le Goff.[4-5]
Dr Gross has previously demonstrated the electrochemical detection of nitrate and nitrite in the presence of oxygen.[6] The BioSEN team also has extensive expertise in the electrical wiring of enzymes at nanostructured electrodes, including Dr Le Goff's work on the oriented, non-covalent wiring of nitrite reductase at carbon nanotubes. Stéphane Marinesco (CRNL) contributes complementary expertise in brain microelectrochemistry and in vivo models of ischemia and stroke, including microsensor-based NO monitoring in rats.

3. THESIS SUPERVISION
Progress will be monitored through regular supervisory meetings (weekly or biweekly) with the student who will present results at the meetings for feedback and discussion. Such meetings will provide a platform for the student to share any difficulties and challenges, and will help the team to identify strategies to successfully achieve project objectives. The PhD researcher will benefit from an Individual Monitoring Committee (Comité de Suivi Individuel, CSI). The PhD researcher will submit an annual progress report and undergo an annual interview with the CSI for the first 2 years. The PhD researcher will naturally participate in local team meetings. Exchanges with external collaborators, particularly the CRNL, and potentially the UGA Faculty of Medicine and/or CERMAV, will take place by videoconference or on site.

4. SCIENTIFIC, MATERIAL AND FINANCIAL CONDITIONS
The general equipment required to carry out the project is available at DCM and through our collaborators and partner facilities. In vivo experiments in rats will be performed within the CRNL team. Certain characterisation techniques that are not directly available at our sites may be required or beneficial to the project, for example X-ray photoelectron spectroscopy (XPS). In vitro and in vivo experiments involving human biological samples or animals must be performed in strict accordance with ethical and safety regulations. The PhD researcher must comply with internal regulations and health and safety procedures at DCM and partner laboratories.
The project will involve the use of certain toxic solvents and reagents, including organic solvents, methacrylation and diazotisation reagents, as well as nanomaterials. Standard safety procedures must therefore be followed, including the use of protective eyewear, gloves, laboratory coats and appropriate fume hoods, including a dedicated nanomaterial fume hood.

Location:
1. Département de Chimie Moléculaire (UMR 5250), 570 Rue de la Chimie, Université Grenoble Alpes, 38610 Gières, France (primary).

Partner location for in-vivo experiments
2. Université Claude Bernard Lyon 1, CNRS UMR5292, INSERM, Centre De Recherche En Neurosciences De Lyon CRNL U1028 UMR5292, Team TIGER, F-69500 Bron, France.

This ANR-funded PhD project (NeuroNOx, 2026-2030) involves an important collaboration with Dr Marinesco and his team for in-vivo experiments in the brain. The PhD researcher will share samples and participate in short research missions to the Lyon-based laboratory to advance the in-vivo aspect of the work. The successful candidate will work with a second PhD researcher (due to start on 01/12/2026 under the direct of Dr Gross with Prof. R. Auzely) developing complimentary strategies for in vivo biomarker monitoring, providing an attractive collaborative local research environment. A postdoctoral researcher will be recruited later in this ANR project to assist with in-vivo experiments. This project will also benefit from collaborations with the Faculty of Medicine and CERMAV institute at Université Grenoble Alpes (UGA).

5. DISSEMINATION, PUBLICATIONS AND CONFIDENTIALITY
Participation in regional, national and international conferences will be encouraged. Attendance at scientific events is important for developing scientific communication skills and disseminating research results. The PhD researcher will also be involved in the preparation of scientific publications. Some results may be patented. Any public dissemination of results must therefore receive prior approval from the PhD direction. This research project is located within a Restricted Access Zone (Zone à Régime Restrictif, ZRR) under the French Protection of Scientific and Technical Potential (PPST) framework. Local confidentiality rules must be strictly respected.

6. PROFILE AND SKILLS REQUIRED
• A background in electrochemistry or bioelectrochemistry is required, with a Master's degree or equivalent.
• A strong interest in or knowledge of biochemistry, particularly enzymes and nitric oxide biology, would be highly appreciated.
• Skills in surface functionalisation and characterisation would be an advantage.
• A critical and analytical mindset, self-motivation, creativity and curiosity are essential.
• Ability to work both independently and as part of a team on multidisciplinary topics.
• English: B2 level required as a minimum; C1 level preferred (or equivalent)

7. APPLICATION PROCEDURE
Candidates should provide:
• a CV
• a motivation letter

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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