title: Development of Microelectrode Arrays Using Electroless Plating for CMOS-Based Direct Counting of Bacterial and HeLa Cells.
abstract: The development of two new types of high-density, electroless plated microelectrode arrays for CMOS-based high-sensitivity direct bacteria and HeLa cell counting are presented. For emerging high-sensitivity direct pathogen counting, two technical challenges must be addressed. One is the formation of a bacteria-sized microelectrode, and the other is the development of a high-sensitivity and high-speed amperometry circuit. The requirement for microelectrode formation is that the gold microelectrodes are required to be as small as the target cell. By improving a self-aligned electroless plating technique, the dimensions of the microelectrodes on a CMOS sensor chip in this work were successfully reduced to 1.2 μm × 2.05 μm. This is 1/20th of the smallest size reported in the literature. Since a bacteria-sized microelectrode has a severe limitation on the current flow, the amperometry circuit has to have a high sensitivity and high speed with low noise. In this work, a current buffer was inserted to mitigate the potential fluctuation. Three test chips were fabricated using a 0.6- μm CMOS process: two with 1.2 μm × 2.05 μm (1024 × 1024 and 4 × 4) sensor arrays and one with 6- μm square (16 × 16) sensor arrays; and the microelectrodes were formed on them using electroless plating. The uniformity among the 1024 × 1024 electrodes arranged with a pitch of 3.6 μm × 4.45 μm was optically verified. For improving sensitivity, the trenches on each microelectrode were developed and verified optically and electrochemically for the first time. Higher sensitivity can be achieved by introducing a trench structure than by using a conventional microelectrode formed by contact photolithography. Cyclic voltammetry (CV) measurements obtained using the 1.2 μm × 2.05 μm 4 × 4 and 6- μm square 16 × 16 sensor array with electroless-plated microelectrodes successfully demonstrated direct counting of the bacteria-sized microbeads and HeLa cells.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Niitsu
authors.forename: Shoko
authors.initials: S
authors.lastname: Ota
authors.forename: Kohei
authors.initials: K
authors.lastname: Gamo
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kondo
authors.forename: Masaru
authors.initials: M
authors.lastname: Hori
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakazato
mesh_terms: D001419:Bacteria; D001698:Biomedical Engineering / Q000295:instrumentation; D002452:Cell Count / Q000295:instrumentation*; D004867:Equipment Design; D006367:HeLa Cells; D006801:Humans; D046228:Microarray Analysis / Q000295:instrumentation*; D008839:Microelectrodes; D019095:Point-of-Care Systems; D012666:Semiconductors