Biosensor integration on Si-based devices: feasibility studies and examples

Feasibility studies and examples of integration of Si-based miniaturized biosensors are discussed. We investigated three main issues: (i) device surface functionalization, (ii) biological molecule functionality after immobilization and (iii) biosensor working principle using electrical transduction mechanism in order to fabricate electrolyte-insulator-semiconductor (EIS) and, in the near future, ion-sensitive field-effect transistor (ISFET) biosensors. We compared a well established method for the immobilization of bio-molecules on Si oxide with a new immobilization protocol, both providing a covalent bonding on SiO2 surfaces of proteins (metallothioneines) enzymes (glucose oxidase, horse radish peroxidase), or DNA strands. The process steps were characterized by means of contact angle, XPS and TEM measurements. The compatibility with Ultra Large Scale Integration (ULSI) technology of the two protocols was also studied. The results strongly encourage to use the new optimized protocol to accomplish both ULSI compatibility and biological molecules correct functionalization. The electrical characterization of MOS-like capacitors with ssDNA anchored on the SiO2 dielectric, allowed us to conclude that the structures tested are sensitive to DNA immobilization and hybridization, as demonstrated by a positive shift in the V-FB of +0.47 +/- 10.04 V after ssDNA immobilization and by a further +0.07 +/- 1 0.02 V shift when hybridization occurs. Device working principle was proved in this way. However, our results seem to indicate that bare SiO2 surfaces cannot be used as anchoring sites for DNA in transistor applications. In fact, the immersion in solution causes the migration of H+ ions in the oxide and the formation of defects at the SiO2/Si interface.