ARTEMIDE
“Autonomous Real Time Embedded Multi-analyte Integrated Detection Environment"
ARTEMIDE is a PRIN national project with the objective to develop a fully integrated lab-on-chip system for the early diagnosis of viral infections.
Role: Partner
Activity period: 2013-2016
Research Line: Optical Nanosensing
Proposal core of the Encoder project is the development and characterization of complex nanostructures for therapy/sensing and multimodal diagnosis/imaging applications in pathologic cardiac hypertrophy.
TThe goal of the ARTEMIDE project was the fabrication of lab-on-chip systems that integrate in a single device all the functional modules needed for the rapid and reliable execution of complete bio-analytical protocols. The diagnosis of infections caused by model viruses such as parvovirus B19 (B19V) and human papillomavirus (HPV) have been selected as target analytical applications for the proposed project. The target was to go beyond the conventional lab-on-chip devices that are generally limited to microfluidic networks that implement analytical protocols but need bulky instrumentation to be operated (pumps, microscopes, scanners).
The ARTEMIDE project aimed then at the integration of on-chip sensors, actuators, functional surfaces and special analytical protocols in a single ‘true’ lab-on-chip device. In particular, the project aimed at the development of the competencies, the technologies and the analytical protocols that enable the fabrication of a completely stand-alone microsystem composed of the lab-on-chip itself, the embedded electronic system and the analytical chemistry based on bio-/chemiluminescence reactions that allow the simultaneous quantification of biomarkers of viral infections (minimal or non-invasive diagnosis). This multidisciplinary project was focused on different topics:
1) on-chip integration of sample pretreatment functionalities including DNA amplification;
2) integration of autonomous microfluidic networks with on-chip actuators for the handling of samples and reagents;
3) introduction of highly specific bio- or chemi-luminescent reactions for analytical detection;
4) fabrication of thin-film hydrogenated amorphous silicon (a-Si:H) sensors on the same substrate of the microfluidic chip;
5) design of an embedded system including all the electronics for the control of the lab-on-chip as well for the real-time data analysis.
The main project goal implied the achievement of fundamental milestones for the six research units participating to the project. These milestones can be grouped in four fundamental groups:
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Analytical biochemistry.
Development of efficient and selective DNA amplification processes to be implemented on-chip. Development of analytical protocol for the chemiluminescent detection of the target molecules. Development of methods for the determination of bioanalytical ultrasensitive marker of viral infection in the form "hybrid" antibodies (and DNA).
- 2) Design and modeling of the subsystems. Analysis of functional aspects. Modeling of luminescence phenomena.Building guiding structures on the substrate to optimize the optical coupling between the signal source which is placed on the surface of the labon- chip and the photosensors.
- 3) Technological development. Integration onto a single substrate of all the elements necessary for the processing and the analysis of the sample, from the microfluidic systems for the control of the biochemical reactions to the radiation sensors for the detection of specific bio-chemiluminescence signals. Identification of materials that meet biocompatibility specifications and at the same time enable the integration of the different parts in a simple and reliable way. Development of methodologies and processes for the chemical immobilization on a single substrate of different classes of molecules with very different characteristics as nucleic acids and proteins. Development of microfluidic systems that enable the handling of fluids without the need for external pumping systems and, more importantly, without the need for interfaces between micro-and macrofluidics.
- 4) System aspects. System integration and operation. Design of the electronic interface for the lab-on-chip device. Development of control and processing algorithms to be implemented using reconfigurable systems. Finally, concerning the scientific research aspect, the ultimate goal of the project was the consolidation of cooperative relations among the various research units and also with international research institutions in order to provide a solid starting point for further developments and applications to be explored in future research projects.
The main activities of the Chemical and Biochemical Optical Sensor Group was focused on the development of the microfluidics for the reaction site module of the optoelectronic Lab-on-Chip system, as well as on the design, implementation and characterisation of the multichannel chip for the simultaneous detection of bioanalytes. In particular, the microfluidics for the microfluidic channels, each of them dedicated to the detection of a single analyte was carefully studied. The structure of the multichannel chip was designed and implemented in strict collaboration with the research units UniRM1, UniPI e UniBO so as to optimise both the bio/chemiluminescent reactions and the collection of the optical radiation emitted by the sensing layer immobilised along the microchannels by the optical waveguides integrated within the glass substrate.
