We have developed an LSI-based amperometric sensor called "Bio-LSI" with 400 measurement points as a platform for electrochemical bio-imaging and multi-point biosensing. The system is comprised of a 10.4 mm × 10.4 mm CMOS sensor chip with 20 × 20 unit cells, an external circuit box, a control unit for data acquisition, and a DC power box. Each unit cell of the chip contains an operational amplifier with a switched-capacitor type I-V converter for in-pixel signal amplification. We successfully realized a wide dynamic range from ±1 pA to ±100 nA with a well-organized circuit design and operating software. In particular, in-pixel signal amplification and an original program to control the signal read-out contribute to the lower detection limit and wide detection range of Bio-LSI. The spacial resolution is 250 μm and the temporal resolution is 18-125 ms/400 points, which depends on the desired current detection range. The coefficient of variance of the current for 400 points is within 5%. We also demonstrated the real-time imaging of a biological molecule using Bio-LSI. The LSI coated with an Os-HRP film was successfully applied to the monitoring of the changes of hydrogen peroxide concentration in a flow. The Os-HRP-coated LSI was spotted with glucose oxidase and used for bioelectrochemical imaging of the glucose oxidase (GOx)-catalyzed oxidation of glucose. Bio-LSI is a promising platform for a wide range of analytical fields, including diagnostics, environmental measurements and basic biochemistry.

We have developed a large-scale integrated (LSI) complementary metal-oxide semiconductor (CMOS)-based amperometric sensor array system called "Bio-LSI" as a platform for electrochemical bio-imaging and multi-point biosensing with 400 measurement points. In this study, we newly developed a Bio-LSI chip with a light-shield structure and a mode-selectable function with the aim of extending the application range of Bio-LSI. The light shield created by the top metal layer of the LSI chip significantly reduces the noise generated by the photocurrent, whose value is less than 1% of the previous Bio-LSI without the light shield. The mode-selectable function enables the individual operation of 400 electrodes in off, electrometer, V1, and V2 mode. The off-mode cuts the electrode from the electric circuit. The electrometer-mode reads out the electrode potential. The V1-mode and the V2-mode set the selected sensor electrode at two different independent voltages and read out the current. We demonstrated the usefulness of the mode-selectable function. First, we displayed a dot picture based on the redox reactions of 2.0 mM ferrocenemethanol at 400 electrodes by applying two different independent voltages using the V1 and V2 modes. Second, we carried out a simultaneous detection of O2 and H2O2 using the V1 and V2 modes. Third, we used the off and V1 modes for the modification of the osmium-polyvinylpyridine gel polymer containing horseradish peroxidase (Os-HRP) at the selected electrodes, which act as sensors for H2O2. These results confirm that the advanced version of Bio-LSI is a promising tool that can be applied to a wide range of analytical fields.