Blanc SVSE 5 - Blanc - SVSE 5 - Physique, chimie du vivant et innovations biotechnologiques

Organic micro-resonators as label-free chemio- and bio-sensors in micro-fluidic environment – MIRODE

Label-free, high-sensitivity and low responde time sensor for chemical and biological applications

The aim of this project is focused on the design, fabrication and validation of e new type of optofluidic label-free sensor based on organic materials, and adapted to chemical and biological applications, in particular for real-time investigations of the dynamics of specific proteins on one hand, and for the detection of heavy ions in water on the other hand

To set-up a multifunctional, ultra-sensitive and ultrafast sensor

The objective is to develop a high-performance, low fabrication cost sensor, liable to detect very small quantities of chemical (pollutants) or biological (proteins, DNA) species. <br />Biology imposes experimental constraints that have not been integrated in the technologies available in other domains. The amount of material available in biological applications is extremely weak, with a wide choice of biological constituents. Progress must be made in terms, not only of sensitivity during measurements, but also in terms of selectivity and reproducibility. Measurements methods must also minimize their effect on the species to be investigated. Therefore, the development of label-free technologies, allowing the observations of molecular interactions without using any fluorescent marker, is a crucial challenge. Among the existing techniques, Surface Plasmon resonance (SPR) has taken the lead at the market level up to now. However, these methods must face problems related to high acquisition noise, then limiting their evolution towards highly sensitive devices, especially for diagnosis applications. <br />The device proposed in this project displays outstanding performances as compared to other state-of the art techniques, especially a low detection limit (about 100 molecules per resonator) and a time response below the millisecond. These perfomances open very attractive perspectives for various applications, especially for the detection of pollutants, and the investigation of the mechanism related to recognition and activity of the biological entities involed in the regulation of gene expression.

- A technology derived from polymer-based optoelectronics : photolithography and etching of optical waveguides and resonators with vertical integartion
- Functionalization methods for biological molecules or for heavy ions ligands on the sensor surface
- Integration in optoelectronic, microfluidic circuits

We have functionalized the microresonator surface (SU-8 polymer) without the microfluidic circuit, and then immobilized a test - bed molecule (TAMRA-cadaverin) on this functionalized surface. Infrared anf fluorescence spectroscopy shows very good results as compared to the functionalization in a SPR device. In our case, a detection limite of 0.22 attogram per resonator has been evidenced.
On another hand, a ligand based on calixarene has been synthsized for lead ion detection.
We have obtained, in the context of d'Alembert Institute, a 40 000 € support from the PALM and nanosaclay Labex, in the frame of their «Valorization« 2012 call.

The funding provided by the two Labex as mentioned above will favor the evolution of the project, which is currently purely basic-research oriented, requiring high-level skills from a physical and technological perspective, towards a user-friendly tool that can be used at a larger scale by non-specialist, in a pluridisciplany environment associating biologists and physicists. This evolution could lead, in a mid-term perspective, to a pre-industrial development.

• Vertically coupled polymer microresonators for optofluidic label-free biosensors ,Delezoide, C.; Lautru, J.; Zyss, J.; Ledoux-Rak, I ; Nguyen, CT., INTEGRATED OPTICS: DEVICES, MATERIALS, AND TECHNOLOGIES XVI Book Series: Proceedings of SPIE Volume: 8264, n° 826416 ( 2012).
• « Vertically Coupled Polymer Microracetrack Resonators for Label-Free Biochemical Sensors », C. Delezoide, M. Salsac, J. Lautru, H. Leh, C. Nogues, J. Zyss, M. Buckle, I. Ledoux-Rak and C.T. Nguyen, IEEE Photonics Technology Letters, 24, n° 4, 270-272 (2012).

This project aims at the design, elaboration, characterization, and validation of a polymer-based, label-free optofluidic sensor for chemical and biological applications, mainly focused toward the real-time investigation of the kinetics of specific proteins on one hand, and the detection of weak concentrations of heavy ions in water on the other hand. Special attention will be paid to the integration of various functionalities (injection and detection of optical signals) of the chip, in order to bridge the gap between laboratory demonstrators (with a limited level of integration) and the miniaturization required for mass production and large-scale use in environmental studies or medicine.
This two-fold set of applications, in biology and water protection, is based on the unique sensitivity of the spectral response of microresonators to the refractive index of their close environment (liquids) or to the composition of the interface between the resonator and the surrounding medium. Elaboration as well as characterization methods are based on common, “generic” techniques, particularly suited for polymer-based devices, with interesting perspectives in terms of large-scale production of low-cost, disposable chips to be used on portable hardware.
We propose a novel label-free biosensor based on a polymeric optofluidic system which not only can display a high sensitivity to the presence of heavy ions or specific biomolecules, but also shows an intrinsic response time of the order of milliseconds, allowing to investigate the kinetics of macromolecular interactions or conformational changes under a continuous monitoring. The chip is based on a polymeric optofluidic system allowing parallel or multiplex measurement. Such a lab-on-chip will be the heart of a future transportable instrument destined for in-situ measurements.
The choice of polymeric materials for the optofluidic sensor system (from elementary cell to biochip) is motivated the large possibility of integration with different inorganic materials thus allowing simple construction of lab-on-chip for biosensing applications. Moreover, many polymeric surfaces can be easily functionalised biochemically in order to attach target biomolecules for specific detection. Finally, polymeric materials are perfectly compatible with microfluidics, thus ensuring an excellent optofluidic integration of biosensors.
The elementary optofluidic cell is composed of a polymeric microring, included in an optical integrated circuit including single-mode input and output waveguides coupled to it, and a microfluidic channel sealed in the upper surface of the optical circuit thus forming an optofluidic circuit. The sensing principle is based on the spectral shift of the optical response of a microrings, induced by the change of refractive index of the microresonator or of its environment or surface state. When coupled to an adjacent waveguide, this response can easily transferred and detected. The originality of this microring consists in its shape (a “race-track” geometry ensuring a long-distance interaction with the coupling waveguides) and a vertical integration between the ring and the input waveguide. This architecture combines three attractive features: high sensitivity related to the underlying physical process, improvement of integration using waveguides vertically coupled to the microsensor, and insertion of the component inside a microfluidic circuit.
The sensitivity of the device to molecular conformation changes will be investigated on microresonators functionalized with a biomolecular recognition layer. Sensitivity to heavy ion concentration will be characterized in order to reach the state-of the art limit on 100 ng:L currently available with non-integrated, non portable set-up. Future developments deal with the elaboration of multiple device array for simultaneous analysis of ions or proteins in the same chip.

Project coordinator


The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.



Help of the ANR 407,743 euros
Beginning and duration of the scientific project: September 2011 - 36 Months

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