Advanced LSI-based amperometric sensor array with light-shielding structure for effective removal of photocurrent and mode selectable function for individual operation of 400 electrodes

Abstract

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.

Electrochemical Arrays for Bioassay Applications

“…A very interesting bioelectrochemical array development has been reported from a collaborative effort in Japan [45]. This team has developed a model 400-element array that uses four measurement modes (open circuit, potentiometric, and two amperometric modes with different applied potentials).…”

Micro/nanoelectrochemical probe and chip devices for evaluation of three-dimensional cultured cells

“…For example, we developed a large-scale integration (LSI)-based amperometric sensor for electrochemical imaging, which was designated the Bio-LSI device. [57][58][59][60][61][62][63][64] This device was applied to the electrochemical evaluation and real-time monitoring of dopamine release from 3D-cultured PC12 cells 62 and ALP activity of EBs. 58 As shown in Fig.…”

Electrochemical Imaging for Single-cell Analysis of Cell Adhesion Using a Collagen-coated Large-scale Integration (LSI)-based Amperometric Device

“…11 An LSI chip was designed by Toppan Technical Design Center Co., Ltd. (Japan), manufactured by SMIC (China), and modified for electrochemical measurements. Briefly, Au electrodes as sensors were prepared on Al pads using lift-off lithography.…”

“…The amplifier consists of a switched-capacitor type I-V converter to amplify the in-pixel signal for amperometric detection. 10,11 The device has been used for the electrochemical imaging of alkaline phosphatase in embryonic stem (ES) cells, 13 A-actinin in differentiated ES cells, 14 and neurotransmitters from PC12 cells. 9 In the present study, the Bio-LSI device was used for the electrochemical imaging of cell adhesion at the single-cell level by monitoring the electrochemical reaction between two redox mediators, [Fe(CN) 6 ] 4¹ and ferrocenemethanol (FcCH 2 OH).…”

“…8 We previously developed a Bio-LSI (large-scale integration) device for the characterization of biomaterials that comprises 400 electrochemical sensors with a pitch of 250 µm arranged to form a LSI-based amperometric device. [9][10][11][12][13][14] The device is based on CMOS technology and an operational amplifier is incorporated into each sensor. The amplifier consists of a switched-capacitor type I-V converter to amplify the in-pixel signal for amperometric detection.…”