LSI-based amperometric sensor for bio-imaging and multi-point biosensing

Abstract

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.

Microchemistry- and MEMS-based Integrated Electrochemical Devices for Bioassay Applications

“…[59][60][61][62][63][64][65][66][67][68] For instance, Lindau and colleagues reported the development of a complementary metal oxide semiconductor (CMOS)-based chip containing 10 © 10 microelectrodes for use in the detection of dopamine. 68 We developed an LSI-based amperometric sensor for electrochemical imaging, [69][70][71][72] designated the Bio-LSI system, first reported by Inoue et al 69 The Bio-LSI system is based on CMOS technology and provides higher temporal resolution for the detection of electrochemical species at different locations on the chip. The Bio-LSI chip is comprised of 400 sensors with a pitch of 250 µm (Fig.…”

Bioimaging with Micro/Nanoelectrode Systems

“…9). 11 Our concept for Bio-LSI is a fusion of Bio-MEMS and an active pixel sensor array to realize a "CMOS video camera for amperometric bioimaging". Sensing points are arranged to form a 20 × 20 array with a 250 μm pitch.…”

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

“…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.…”