DS0710 - Micro et nanotechnologies pour l’information et la communication

Clip-on Optical Biosensor Platform – CLIPO

Clip-on Optical Biosensor Platform

The CLIPO project (CLIP-On optical biosensor platform) aims at the realization of a lens-less and cost-effective biosensing system, for applications in the area of point-of-care biomolecular screening.

Context and challenges of CLIPO

High-throughput screening is an essential tool for early disease detection (e.g., cancer or infectious diseases). There are strong economic interests and societal issues to develop low-cost diagnosis systems, both in developing countries where preventing epidemics at the early stage is crucial, and in developed countries where the cost of healthcare becomes an important issue. The CLIPO project aims at developing and demonstrating a cost-effective and handheld optical system for reliable, multiplexed label-free biosensing, which offers a high potential to greatly overcome the current sensitivity limits of the existing systems. The heart of the system is a clip-on disposable optical chip consisting of an array of nanophotonic biosensors. The whole sensor array is illuminated by an extended VCSEL light source (@948nm), and the sensor response is read in transmission on a CCD camera (see figure). Such a system raises 3 great challenges: the first one lies in the area of Photonics and concerns the design and demonstration of a sensor chip simultaneously yielding high figures of merit for biosensing and low crosstalk between the sensors; the second is both technological and biochemical, as the sensitivity and reliability of a sensor chip strongly depends on the reproducibility of the sensor responses within the sensor array; the third challenge is more market-oriented and consists in achieving high-performance detection while designing optical solutions compatible with cost-effective handheld systems (illumination, detection, alignment) and cost-effective sensor chips (materials, fabrication).

The proposed strategy for the sensor chip is to exploit photonic crystals that enable to design surface-addressed, compact and high-performance sensors. The devices are sensitive to refractive index variations induced by bio-affinity events in presence of the analyte ; such variations lead to wavelength shifts of the sensor resonances, which are monitored in the transmission signal. The operating wavelength is set around 950 nm, which allows to benefit from the low cost of optical components : a single VCSEL light source and a CCD image sensor. In terms of fabrication, the material system is based on standard silicon-on insulator, in order to benefit from the high-performance and large-scale micro-processing technologies. These choices induce several challenges concerning the nanophotonic chips : e.g., the design of photonic-crystal sensors based on silicon and yielding high performances in the absorbing range of the material, or the realization of devices having critical dimensions pushing the limits of standard micro-processing lithography techniques. In order to tackle these issues, thorough investigations of both optical and technological solutions are conducted, and alternative routes are also explored.

The first realizations of the CLIPO project will be presented once published.

The CLIPO project has a strong potential impact in various domains. Besides the advances and the exploration of new ideas in the area of photonics, the technological developments performed in the framework of the project will push further the limits of device feasibility. In particular, large-scale nanometric reproducibility is a highly limiting factor that often imposes an additional level of complexity to the devices, e.g., for post-fabrication accurate tuning of their properties, and great improvement of reproducibility could lead to simplified and more cost-effective device designs and fabrication. In the particular application to biomolecular screening, the CLIPO project should lead to great advances, as the currently existing systems strongly suffer from the need to compromise between the sensing performances, the compactness and the cost of equipment. From a research perspective, the approaches and experimental processes developed here could be exploited and applied to “real case” biomolecular screening, e.g. to the extensive research activities for illness markers. From a more economical perspective, the works performed in the project and the final demonstrator should constitute the basis for the development of fully-integrated handheld optical systems with direct applications as point-of-care (POC) tools. Here, Avalun’s experience in developing POC devices will be of great value for transferring the first proof of concept into a proof of product. The direct outcome for the industrial partner would be the opening a new potential market.

N. Gaignebet, A. Pasecan, L. Berguiga, T. Benyattou, C. Jamois, “Demonstration of slow Bloch mode cavity sensors”, Poseidon Summer School “Photonics for Health”, 18-22 juin 2017, San Martino di Castrozza, Italie N. Gaignebet, A. Pasecan, L. Berguiga, T. Benyattou, C. Jamois, “Demonstration of slow Bloch mode cavity sensors”, IQP Winter School, 26 mars – 1er avril 2017, Trento, Italie

High-throughput screening is an essential tool for early disease detection (e.g., cancer or infectious diseases). There are strong economic interests and societal issues to develop low-cost diagnosis systems, both in developing countries where preventing epidemics at the early stage is crucial, and in developed countries where the cost of healthcare becomes an important issue. The industrial collaborative research project (PCRE) CLIPO aims at developing and demonstrating a cost-effective and handheld optical system for reliable, multiplexed label-free biosensing, which offers a high potential to greatly overcome the current sensitivity limits of the existing systems.
The heart of the system is a clip-on disposable optical chip consisting of an array of nanophotonic biosensors that are read using a lens-free camera. The biosensors are separated by highly-insulating optical barriers ensuring high signal-to-noise ratio of the detected signal and low crosstalk between sensors. The strategy to achieve high optical and sensing performances relies on the use of photonic crystals to realize both the active sensor array and the insulating barriers. The clip-on chip will use mature silicon technology allowing for low costs and mass production.
In order to yield high performances, the photonic crystal sensors should support a high-finesse resonance that should be highly sensitive to the presence of the analyte. The principle of the system relies on the strong variation of the transmitted sensor response upon biomolecule grafting, with the objective to simultaneously read the whole sensor array. Hence, the targeted system should combine efficient homogeneous excitation of the whole chip by a single light source with reliable monitoring of the resonance variations within each sensor via imaging of the transmitted signals on a detection matrix.
The main objectives of the project are the design and validation of the photonic chip according to the specifications defined for the optical system, the demonstration and optimization of the sensor chip for high-performance biomolecular sensing, and the development of a complete optical system compatible with handheld cost-effective solutions. Three great challenges have to be tackled in order to successfully meet these objectives: the first one lies in the area of Photonics and concerns the design and demonstration of a sensor chip simultaneously yielding high figures of merit for biosensing and high optical insulation between the sensors; the second is both technological and biochemical, as the sensitivity and reliability of a sensor chip strongly depends on the reproducibility of the sensor responses within the sensor array; the third challenge is more market-oriented and consists in achieving the high-performance detection described above while designing optical solutions compatible with cost-effective handheld systems (illumination, detection, alignment) and cost-effective sensor chips (materials, fabrication).
The success of the project relies on the close collaboration between 3 complementary partners: INL (photonics and biosensing), LETI (sensor chip technology, optical system), and the spin-out Avalun (specifications and proof of concept). The work program has been organized around 3 interactive tasks. Task 1 (“Photonic chip”) is focusing on the design, as well as the technological and optical optimization of the photonic sensor chip. Task 2 (“Biosensing”) is dedicated to the demonstration of the chips for biosensing, and the optimization of the sensing performances. Task 3 (“Optical system”) aims at defining the specifications of the optical system in terms of optical solutions, equipment and tolerances, and will lead to a final demonstration of the complete system.
As a conclusion, the project presents high potential impact in multiple areas ranging from fundamental and applied photonics, microtechnology, surface chemistry and biosensing, as well as handheld diagnostic tools.

Project coordinator

Madame Cécile Jamois (Institut des Nanotechnologies de Lyon)

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.

Partner

INL - CNRS Institut des Nanotechnologies de Lyon
CEA-LETI-DOPT CEA-LETI, Département d'Optronique
Avalun Avalun

Help of the ANR 540,473 euros
Beginning and duration of the scientific project: October 2015 - 42 Months

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