On-chip integrated lensless microscopy module for optical monitoring of adherent growing mammalian cells

摘要

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 µm thick silicon nitride (Si3N4) substrate onto the surface of a 5 megapixel CMOS image sensor with 2.2 µm 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 Si3N4-membrane as well as in cavity chips with membranes made from dry film resist (DFR, thickness 20, 40 and 60 µm). 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 Si3N4 substrate for 2 days and by checking the colorimetric staining of cells with a compromised membrane.