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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 &#x03BC;m &#x00D7; 2.05 &#x03BC;m. 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- &#x03BC;m CMOS process: two with 1.2 &#x03BC;m &#x00D7; 2.05 &#x03BC;m (1024 &#x00D7; 1024 and 4 &#x00D7; 4) sensor arrays and one with 6- &#x03BC;m square (16 &#x00D7; 16) sensor arrays; and the microelectrodes were formed on them using electroless plating. The uniformity among the 1024 &#x00D7; 1024 electrodes arranged with a pitch of 3.6 &#x03BC;m &#x00D7; 4.45 &#x03BC;m 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 &#x03BC;m &#x00D7; 2.05 &#x03BC;m 4 &#x00D7; 4 and 6- &#x03BC;m square 16 &#x00D7; 16 sensor array with electroless-plated microelectrodes successfully demonstrated direct counting of the bacteria-sized microbeads and HeLa cells.

Development of Microelectrode Arrays Using Electroless Plating for CMOS-Based Direct Counting of Bacterial and HeLa Cells