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

• Published in: Lab on a chip 2012-09, Vol.12 (18), p.3481-3490
• Main Authors: Inoue, Kumi Y, Matsudaira, Masahki, Kubo, Reyushi, Nakano, Masanori, Yoshida, Shinya, Matsuzaki, Sakae, Suda, Atsushi, Kunikata, Ryota, Kimura, Tatsuo, Tsurumi, Ryota, Shioya, Toshihito, Ino, Kosuke, Shiku, Hitoshi, Satoh, Shiro, Esashi, Masayoshi, Matsue, Tomokazu
• Format: Article
• Language: English
• Subjects: Biosensing Techniques; Electrochemical Techniques - instrumentation; Electrochemical Techniques - methods; Enzymes, Immobilized - chemistry; Enzymes, Immobilized - metabolism; Glucose - analysis; Glucose Oxidase - chemistry; Glucose Oxidase - metabolism; Horseradish Peroxidase - chemistry; Horseradish Peroxidase - metabolism; Hydrogen Peroxide - chemistry; Oxidation-Reduction
• ISSN: 1473-0197; 1473-0189
• DOI: 10.1039/c2lc40323d

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.