Process development for novel low temperature plasma synthesized nanocarbon-based biosensors – PlasBioSens

The work in progress includes several different methods and technologies concerning development of processes for synthesis of materials, analysis of processes and materials, development of transistors and biological tests, as following:
- Plasma technology for synthesis of carbon based nanomaterials (PECVD, sputtering) and their functionalization (by functional groups or coatings)
- Plasma diagnostics (electron density measurements, mass-spectroscopy, in-situ FTIR)
- Material analysis (laboratory methods: FTIR, Raman spectroscopy, electron microscopy-SEM and TEM ; synchrotron analysis: XPS and NEXAFS)
- Clean room/ microelectronic technology for development of transistors
- Methods for diagnostics of transistors- for example electrical measurements, uniformity, reliability
- Biological tests/ immunochemistry: protein detection, asthma models, ELISA ...

The work on carbon based nanomaterials (CBNs) resulted in materials that are mechanically and chemically stable, especially concerning the applications- stability as a sensor part and stability in biological fluids. For MWCNT-c a new method for catalyst treatment and nanotube growth - where all steps are performed with a plasma- was successfully applied. The porous carbon thin films (PCTF materials) were obtained by selective etching of copper in copper/carbon thin films deposited by co-sputtering of a copper, and a graphite target. The work on functionalization was obtained by means of simple nitrogen containing ccrf plasma functionalization, and by deposition of ultrathin polymer layers.
First tests in biological liquids were performed- with BSA (bovine serum albumine) and will be followed with HRP (Horse radish peroxidase). Asthma models have been run in mice to develop allergic response and ovalbumin IgG and IgE responses. Specific IgE detection has first been performed in ELISA. Other allergens such as Betv1 for birch pollen allergen were tested, the in vivo model established and the presence of specific IgE in serum characterized by ELISA.
IETR was concentrated on the production of several surfaces for the development of CBN-systems to test the compatibility with the functionalization protocol and on the design of the masks, and the development and optimization of the technological processes for the production of field effect transistors. The optimization of the process concerned: a) gate insulator multilayer (optimization of the thicknesses), b) insulator for sensor surface and c) reduction of thickness of the sensitive layer. For this part deliverables are: fabrication of transistor with good electrical characteristics, especially with a decrease of the threshold voltage and a good uniformity (measured with field effect mobility dispersion). Structures are ready for functionalization, whereas the optimization of the design is in progress.

Several types of conductive carbon based nanostructures are synthesized (nanotubes, nanoparticles to nanowalls) and characterized (2 measurement campaigns at Synchrotron facility -HZB Berlin), also with external cooperation partners (e.g. CEA Kiel, Germany; IST, Lisbon, Portugal). The development of the surface functionalization procedure resulted in deposition of ultrathin conductive polymer films containing amino groups. The polymer introduction system was finally not bought ready-made, but co-developed with Omicron Technologies, SME from Lyon. Omicron Technologies will use the results for one new device that will be offered to academic as well as to industrial customers, in final ready-to-use- version.
The fabrication of transistors with good electrical characteristics, especially with a decrease of the threshold voltage and a good uniformity is achieved. The results of material synthesis were for the first time, and very successfully, combined with transistors: relatively low temperature used to synthesize PCTF opens the way for their deposition on the active surface of sensors. Their integration in a MOSFET sensor without affecting the electrical characteristics has been demonstrated. This first result is more than promising for FET based sensors technologies requiring carbon electrode with a highly active specific surface area. Asthma models have been run in mice to develop allergic response and ovalbumin IgG and IgE responses. The stability of transistors in contact with biological fluids was tested successfully.
All these steps were crucial for future development of project: further tests with nanofunctionalization (integration of CBNs in transistor) will be performed; CBN-surfaces coated with ultrathin layers blocking contact between biomolecules and metals; further steps concerning functionalization of surfaces with specific proteins are planned for the next period (T18-30). Patterning and miniaturisation should be performed on all CBN types.

2 papers in review process, 2 in preparation, 6 presentations at international conferences, e.g.:
1. S Hussain, E Kovacevic, Quesniaux, M Alaaeddine, Ch. Boulmer-Leborgne,et al “Plasma-based synthesis ChemOnTubes Brussels, Belgium, April 3 - 7 2016, talk
2. C. Pattyn, S. Hussain, T. Labbaye, E. Kovacevic, N. Semmar, J. Berndt, A. Stolz, T. Lecas, Ch. Boulmer-Leborgne, A. Jagodar, M.R. Ammar, A. Canizares, P. Simon, S. Rose, V. Quesniaux: E-MRS Spring meeting May 2-6,2016, Lille, France, talk
3. E. Kovacevic Sh. Hussain, A. Jagodar, C. Pattyn, Ch. Boulmer-Leborgne, I. Stefanovic, V. Quesniaux et al. Carbon nanostructures from plasma processes as a base for novel bio-sensors; ICAPT-5, Feb 2016, Rogla, Slovenia; invited
4. L. Donero, F. Le Bihan, L. Le Brizoual, A. El Mel; P.-Y. Tessier, Micro-sensors nano-functionalized for chemical detection, 11th International Thin-Film Transistor Conference, ITC2015, Rennes, France, February 26-27, 2015.
5. L. Donero, N. Bouts, A. A. El Mel, B. Le Borgne, L. Le Brizoual, F. Le Bihan and P.-Y. Tessier, From copper/carbon thin films to nanoporous carbon for sensing applications, E-MRS Spring Meeting, Lille, France, May 2-6, 2016.
6. E. Kovacevic, Ch. Boulmer-Leborgne, V. Quesniaux, S. Rose et al. “Amélioration du procédé de croissance de nanotubes de carbone et fonctionnalisation des tapis de nanotubes pour une application biocapteur” MATV2L, Orléans, March 16-17 2016.
7. L. Donero, F. Le Bihan, L. Le Brizoual, R. Rogel, A.A. El Mel, P.Y. Tessier, Optimisation technologique de transistors pour le développement de microcapteurs chimiques nano-fonctionnalisés JNRDM2015, Bordeaux, 5-7 mai 2015.
8. A. Dias, E. Tatarova, J. Henriques, E. Kovacevic, J Berndt et al., 28th SPPT, Prague, Czech Republic, June 16-20 2016, EPS Poster Prize
9. E. Kovacevic : Plasma based process for development of biosensors, 08/10 2015 JOCA, Orléans
10. E. Kovacevic et al : presentation of PlasBioSens at GDR ABioPlas December 2015, Orléans

The main objective of the project is the development of novel methods for the synthesis and functionalization of conductive nanocarbons for a new generation of field effect transistor sensors suitable for high sensitivity bio-sensing applications.

This highly interdisciplinary research will be performed by 4 complementary laboratories: plasma-processing, nanomaterials, electronics, biology. Advanced carbons (carbon nanotubes, carbon-metal nanocomposites…) will be synthesized and primary functionalized by means of low temperature plasma-based techniques.

Numerous in-situ diagnostics of the plasma will be performed in combination with the surface analysis to understand and control the grafting of functional groups at carbon surfaces.

This will enable the targeted coupling of antibodies/proteins important for development of sensors for the detection of allergens or allergy markers in biological fluids.

The knowledge transfer is targeting the field of the technological/industrial applications of plasma discharges as well as the the material and sensor production.