Development of 2-dimension microscale separation system and technology for characterization of nanoparticles towards nanomedicine applications

This project aims at developing a novel concept in separation science and a new system called microscale 2D magneto-electrography (2D-ME). This concept will allow two simultaneous orthogonal migration dimensions in the same microchannel: capillary electrophoresis (CE) under a high electric field and magnetophoresis under a powerful magnetic field gradient. This new concept is expected to be better adapted for size, charge and shape characterization of nano objects (e.g., functionalized nanoparticles).

Nanoparticles (NPs), including magnetic nanoparticles (MNPs) play important roles in diagnosis, drug delivery systems and nanomedicine.   Particularly for MNPs, size is also a key parameter when using them as contrast agents in magnetic resonance imaging or tumor radio-sensitization, for magnetic hyperthermia dedicated to thermosensitive drug delivery or cancer treatment [1]. For each family of MNPs, there is often a co-existence of various subpopulations and interferences (especially in biological fluids) with overlapping physical properties, rendering challenging their fine separation and characterization. This requires qualified methods to well separate their subpopulations and characterize them, in order to improve their synthesis to obtain the desired MNPs quality, which is mandatory for biomedical applications and drug delivery systems.

Recently, particular attention has been paid to anisotropic MNPs with elongated shapes such as nanorods or nanochains as they exhibit improved magnetic properties for magnetic resonance imaging and magnetic hyperthermia in comparison to their spherical counterparts [2]. Such anisotropic MNPs are also featured by a higher blood circulation time and a prolonged retention in tumor sites compared to spherical NPs, as well as improved interaction with cells thanks to their cylindrical shape. It is however very challenging to separate and characterize anisotropic NPs using conventional separation approaches.

From this urgent need, the first 2D-ME prototype to be developed in microfluidic format will be used for resolute charge, size and shape characterization of spheric MNPs and nanorods serving as innovative drug carriers. 2D-ME will also explore and control the nanometric heterogeneity as well as their interactions with biomolecules (e.g., blood proteins) to improve NPs synthesis and the quality of nanomedicine.

Method and tasks

This interdisciplinary project covers microfluidics, instrumentation, (bio)analytical chemistry, and nanoscience. This project will be supported by the complementary expertise of partners from Institut Néel (for magnetic field design modeling and micro-magnet parterning) and the Inorganic Colloids team of laboratory Physico-chimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX, Sorbonne university, for synthesis and characterization of magnetic nanoparticles).

The PhD student will develop the 2D-ME system and protocols for pre-concentration, separation and characterization of tailored spheric MNPs synthesized by PHENIX. The 2D-ME system in microfluidic format will be developed, with the strong support of our group in purpose-made microfluidic and electrokinetic instrumentation [3, 4]. The PhD student will start from the new microfluidic capillary electrophoresis setup that has been developed in 2024 in the host laboratory.

The PhD student, in close collaboration with Institut Néel, will try to propose different ways to combine the magnetic and electric fields in a microchannel to carry out 2D-ME of standard MNPs. The PhD student will then demonstrate the applicability of the developed system and methodology for separation of magnetic nanorods provided by PHENIX and monitoring their interaction with human plasma proteins to evaluate their behavior under biological conditions.

“Protein and Nanotechnology in analytical Science” (PNAS) is one team of the Institut Galien Paris-Saclay (IGPS, UMR CNRS 8612) located at the Faculty of Pharmacy of University Paris-Saclay. IGPS is an interdisciplinary research unit in pharmacy, biopharmaceutics, pharmaceutical technology and analytical chemistry for diagnostics. The institute is considered as one of the main actors in the field of nanoscience and nanomedicine in Europe. The PNAS team is internationally recognized for its developments of original electrokinetic-based methods and instrumentation for proteins and nanoparticles serving for diagnostics and drug delivery.  IGPS has developed new concepts in analytical science, notably Lab-in-Droplet, Lego-toy CE, and multi-model detection system. The team has a longstanding and well-established expertise in developing new concepts and (miniaturized) diagnostic tools. PNAS has been participating actively in the creation and promotion of a national scientific group on capillary electrophoresis. It is a member of the LERMIT laboratory of excellence (Labex) and leads the SysABCD (Analytical Systems for Biomarkers and Sustainable chemistry) project which is a Strategic Research Initiative of University Paris-Saclay. The laboratory is equipped with UHPLC, nano LC, HPLC and CE instruments, with different detection modes (LIF, UV, QTOF-MS…) as well as the instrumental park consisting of various purpose-made microfluidic and electrokinetic devices (e.g., modular CE system, droplet manipulator, lab on chip and non-clean-room microfabrication platform). IGPS-PNAS has experience in technology transfer and valorization.

Required competences

• You are highly motivated to work at the boundary between microfluidics, instrumentation, bioanalytical chemistry and nanoscience.

• You have a master’s degree or equivalent (obtained within 4 years) in either Microfluidics, Nanoscience, Instrumentation or Analytical Chemistry

• You have practical experience in microfluidics and / or  analytical chemistry

• Good knowledge about biochemistry and nanoparticles is advantageous.

• You have strong communication and presentation skills in English (verbal and written)

• You enjoy working independently and challenging scientific obstacles with an optimist aptitude.