Nano-DSC: Differential scanning nanocalorimetry for life sciences and nanosciences applications – Nano-DSC

The project's success is based on five complementary and essential skills : Microfabrication and microtechnologies : The differential microsensor is obtained thanks to the technologies of microelectronics. The principle of suspended polymer membrane and microphotolithographied thin metallic films allows a reduction in mass of the sensitive aeras, that allows the analysis of small samples. Low noise integrated electronic : increasing the signal to noise ratio of the sensor in reducing the measurement noise and increasing its sensitivity is essential for the detection of small thermal events microliter samples. Thermal conditionning of the sensor : temperature stability of the sensor depends on its thermal conditioning. An ultra-stable thermal environment based on original mounting of the temperature regulated shields is proposed. The system alternates heating resistance and Peltier elements for cooling. Thermal denaturation of biological systems models : targeted applications deal with the field of biophysics. Knowledge in this field of one of the project partners is essential to validate the performance of the instrument. Valorisation and potential industrial applications : patent deposition, patent landscape, marketing, is ensured by a specialized partner.

Performances of the differential micro-sensor in a simplified surroundings were obtained : the power sensitivity is of 2.5 mV / mW. The limit of detection in the final ultra-stable thermal environment will be only of few nanowatts.

The ultra-stable environnement has a thermal stability on the last stage of regulation of 10 µ°C peak to peak. The first results were obtained on the detection of crystalline phases transition on 1 microliter of PTFE polymer, on the melting and crystallization of 1 microliter of liquid water, as well as on the detection of the thermal denaturation on 1 microliter of diluted protein in solution (bovine alpha-lactalbumin) with a concentration of 10 mg / ml. As a consequence this last measure has required only 10 microgramms of protein. The industrial transfert will be effective via a collaboration with an industrial partener in the field or via the creation of a start-up inside the laboratory.

The main advantage of the prototype is to analyze solid or liquid samples in very small quantities thanks to an high-resolution thermal method. In particular, liquid samples are enclosed in microcontainers. They have been specifically developed to maximize the thermal contact with the sensitive area of ??the micro-sensor but without adding too much addenda (heat capacity of the containers is of the order of mJ /K). Potentialities of this original instrumentation in thermal analysis can complement those usually carried out in laboratories and industries working in the field of biophysics or life sciences. Let us remember that only thermal or calorimetric analysis directly provide essential thermodynamic data for a complete characterization of a biological sample (protein, DNA, viruses, ...).

1. Patent CNRS-SETARAM n°1155432 du 21/06/11 « Capteur de mesure calorimétrique différentiel et procédé de fabrication » An industrial partner is involved in this first phase. The PCT application was filed on 18/06/2012 (PCT/IB2012/053057)
2. Filed patent relating to « Environnement contrôlé pour mesures nanocalorimétriques» being written. This ultra-stable thermal environment, dedicated to the differential microsensor, is an essential technological element for the achievement of high resolution nano-calorimetric measurements on microliter biological samples in aqueous solutions.

This innovative experimental project is located at the ultimate limit of the instrumentation in calorimetry, with a strong interdisciplinary component (instrumental physics, life sciences).

It aims to develop a prototype of differential scanning microcalorimeter for innovative applications in biophysics, but also in pharmacy or nanosciences. Actually, the new possibility of this microcalorimeter will allow the calorimetric measurements (specific heat, phase transitions) of any type of liquid sample available in small quantity and for which usually the underlying thermal effects are too small to be detected with classical apparatus.

In particular, we suggest, through microfabrication technology and through an integrated low-noise electronic chain to build a prototype of differential scanning nanocalorimeter based on microsensors that can work with microliter volume samples with a sensitivity never reached for these types of devices (about ten nanowatts in limit of detection is planned).

The second part of the project will concern the validation of the performances of this instrument with measurements made on model biological systems (protein in solution). This will be conducted by experts in the field of a possible application (thermal denaturation of proteins) of the demonstrator.

Finally, the objective of industrial valorization, based on several patents, is to initiate the transfer of these instrumental developments towards the industrial world in partnership with an expert company in industrial property.

Due to its performances in terms of sensitivity and low volumes of sample, this nano-DSC opens new fields of applications for fundamental research in life sciences but also in pharmacy, medicine or nanoscience, and consequently for new markets under development.