title: On-chip integrated lensless microscopy module for optical monitoring of adherent growing mammalian cells.
abstract: Lab-on-a-chip systems are increasingly applied in cell-based assays for toxicology and drug testing. In this paper, an on-chip integrated lensless microscopy module using a direct projection method for optical monitoring of the shadow images of adherent growing mammalian cells is presented. The biological cells are conserved and interfaced by a microfabricated cavity chip with a 1 microm thick silicon nitride (Si(3)N(4)) substrate onto the surface of a 5 megapixel CMOS image sensor with 2.2 microm pixel size. The optical resolution of the assembly is estimated by the contact/proximate printing theory from optical lithography. Further characterization is made by imaging microbeads in chips with the Si(3)N(4)-membrane as well as in cavity chips with membranes made from dry film resist (DFR, thickness 20, 40 and 60 microm). The module represents a 3 × optical microscope for cell morphology imaging. The function is demonstrated by the growth monitoring of L929 cells cultured in cavity chips with Si(3)N(4) substrate for 2 days and by checking the colorimetric staining of cells with a compromised membrane.
authors.affiliation: Fraunhofer Institute for Biomedical Engineering, Department of Biohybrid Systems, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Thorsten
authors.initials: T
authors.lastname: Knoll
authors.forename: Hagen
authors.initials: H
authors.lastname: Thielecke
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D007089:Image Enhancement / Q000295:instrumentation*; D007909:Lenses; D008029:Lighting / Q000295:instrumentation*; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D008853:Microscopy / Q000295:instrumentation*; D015203:Reproducibility of Results; D012666:Semiconductors; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted / Q000295:instrumentation*; D018511:Systems Integration