title: Integration of microfluidic and cantilever technology for biosensing application in liquid environment.
abstract: Microcantilever based oscillators have shown the possibility of highly sensitive label-free detection by allowing the transduction of a target mass into a resonant frequency shift. Most of such measurements were performed in air or vacuum environment, since immersion in liquid dramatically deteriorates the mechanical response of the sensor. Besides, the integration of microcantilever detection in a microfluidic platform appears a highly performing technological solution to exploit real time monitoring of biomolecular interactions, while limiting sample handling and promoting portability and automation of routine diagnostic tests (Point-Of-Care devices). In the present paper, we report on the realization and optimization of a microcantilever-based Lab-on-Chip, showing that microplates rather than microbeams exhibit largest mass sensitivity in liquid, while pirex rather than polymers represents the best choice for microfluidic channels. Maximum Q factor achieved was 140 (for fifth resonance mode of Pirex prototype), as our knowledge the highest value reported in literature for cantilever biosensors resonating in liquid environment without electronic feedback. Then, we proved the successfully detection of Angiopoietin-1 (a putative marker in tumor progression), showing that the related frequency shifts coming from non-specific interactions (negative controls) are roughly one order of magnitude lower than typical variations due to specific protein binding. Furthermore, we monitored the formation of antibody-antigen complex on MC surface in real-time. The proposed tool could be extremely useful for the comprehension of complex biological systems such as angiogenic machinery and cancer progression.
authors.affiliation: LATEMAR-Politecnico di Torino, Dipartimento di Scienza dei Materiali ed Ingegneria Chimica, Corso Duca degli Abruzzi 24, I-10129 Torino, Italy. carlo.ricciardi@polito.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Ricciardi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Canavese
authors.forename: Riccardo
authors.initials: R
authors.lastname: Castagna
authors.forename: Ivan
authors.initials: I
authors.lastname: Ferrante
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ricci
authors.forename: Simone Luigi
authors.initials: SL
authors.lastname: Marasso
authors.forename: Lucia
authors.initials: L
authors.lastname: Napione
authors.forename: Federico
authors.initials: F
authors.lastname: Bussolino
mesh_terms: D042683:Angiopoietin-1 / Q000032:analysis; D055910:Antibodies, Immobilized; D000937:Antigen-Antibody Reactions; D014408:Biomarkers, Tumor / Q000032:analysis; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods / Q000706:statistics & numerical data; D018450:Disease Progression; D004867:Equipment Design; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods / Q000706:statistics & numerical data; D009369:Neoplasms / Q000098:blood supply / Q000737:chemistry; D009389:Neovascularization, Pathologic
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D055910:Antibodies, Immobilized; D014408:Biomarkers, Tumor