Keywords :
Biosensor, ISFET, BioFET, pH, ADN, Silicon, Thrombin, Silanization, Diagnosis
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Abstract
For several decades, the race towards the miniaturization and the complexification of electronic functions have led to the integration of innovative materials to maintain the required performance in terms of response time and power consumption. The development of biosensors, which is a subject of an intensive research activity, does not make exception to the rule. Indeed, the coupling of chemical functionalization and nanomaterials (Si nanowires in our case) opens exciting new opportunities for the realization of ultra-scaled sensors, ultrasensitive and selective, used for the detection of chemical and biological species.
In this context, our work aims to develop a biologically sensitive Silicon nanowire-based FET (SiNW BioFET) capable of reliable and ultrasensitive charge detection. Here, we give a proof of principle with pH sensing, electrical detection of DNA molecule hybridization, and electrical detection of thrombin protein by using a specific probe (G-quadruplex thrombin binding aptamer).
Our bioFETs are based on conventional “top-down” CMOS compatible technology to facilitate their integration with signal processing systems. We explored several designs (nanowires (NW), nanoribbons (NR), and honeycomb (HC) structures) with opening access scaled down to only 120 nm.
After device fabrication, IDS-VBG output characteristics show a conventional n-type FET behavior with an ION/IOFF value higher than 10^5, as well as an increase of threshold voltage (Vt) as the NW width is reduced.
During pH measurements (ionic charge measurements) the sensitivity of our BioFETs to pH was evaluated at ~60 mV/pH on different BioFET structures, in accordance with the theoretical limit of Nernst, and regardless of the structures and dimensions considered. We used a capacitive coupling in our dual-gated SiNW bioFETs to obtain an enhanced pH sensitivity up to ~1,57 V/pH.
In a second stage, we successfully detected a 2 μM target DNA molecules through the positive Vt shift that it induced on the output characteristics when a greater number of negative charges –carried by the target DNA strands– is brought through hybridization, in the sensing site of our n-type FET biosensors.
In our latest study, we sought to demonstrate the ability of our devices to detect proteins using aptameric probes. Two biochips were used. The covalent grafting of the aptameric probes on the surface of our devices induced an average shift in the threshold voltage of the grafted devices of +28.8 mV on the first chip, and of +87.7 mV on the second, confirming the effective grafting of the probe molecules on the surface of the gate oxide.
Subsequently, the addition of buffer solutions concentrated at 2.7 µM in thrombin induced an average shift of -26.6 mV on the first chip, and -23.8 mV on the second, shifts relating to the Vt values measured during characterizations of buffer solutions without thrombin (thrombin dilution buffer solution containing 0 µM of thrombin).
Finally, the perspectives of our work concern the integration of a microfluidic system on our chips for real-time biological measurements, multiplexed measurements, the integration of our chips at the "back-end of line" level of a signal processing system, as well as the integration of a reference electrode on the chip, in direct proximity to the measurement cavitiesMembres du jury/ Jury members :
Dr. |
Guilhem LARRIEU |
DIRECTEUR DE RECHERCHE, LAAS-CNRS |
Rapporteur |
Prof. |
Abdelkader SOUIFI |
PROFESSEUR DES UNIVERSITES, INSA LYON |
Rapporteur |
Dr. |
Mireille MOUIS |
DIRECTEUR DE RECHERCHE, CNRS-Alpes |
Examinatrice |
Dr. |
Chantal GONDRAN |
MAITRE DE CONFERENCES Université Grenoble Alpes |
Examinatrice |
Dr. |
Valérie STAMBOULI |
CHARGE DE RECHERCHE, CNRS-Alpes |
Directrice de thèse |
Dr. |
Sylvain BARRAUD |
DIRECTEUR DE RECHERCHE, CEA LETI, |
Thesis co-director |
Dr. |
Pascal MAILLEY |
DIRECTEUR DE RECHERCHE, CEA LETI |
Membre invité |
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