An ISFET Microarray Sensor System for Detecting the DNA Base Pairing.

Huaqing Si,Dan Zhao,Yongxin Cong,Peng Sun,Ming Xu,Dongping Wu

doi:10.3390/mi12070731

Abstract

Deoxyribonucleic acid (DNA) sequencing technology provides important data for the disclosure of genetic information and plays an important role in gene diagnosis and gene therapy. Conventional sequencing devices are expensive and require large and bulky optical structures and additional fluorescent labeling steps. Sequencing equipment based on a semiconductor chip has the advantages of fast sequencing speed, low cost and small size. The detection of DNA base pairing is the most important step in gene sequencing. In this study, a large-scale ion-sensitive field-effect transistor (ISFET) array chip with more than 13 million sensitive units is successfully designed for detecting the DNA base pairing. DNA base pairing is successfully detected by the sensor system, which includes the ISFET microarray chip, microfluidic system, and test platform. The chip achieves a high resolution of at least 0.5 mV, thus enabling the recognition of the change of 0.01 pH value. This complementary metal-oxide semiconductor (CMOS) compatible and cost-efficient sensor array chip, together with other specially designed components, can form a complete DNA sequencing system with potential application in the molecular biology fields.

Highlights

Deoxyribonucleic acid (DNA) sequencing [1,2], detection of the order of nucleotides in DNA strands, plays a significant role in the field of life and health
The core sensor detection and data processing capability of a semiconductor gene sequencer depends on a complementary metal-oxide semiconductor (CMOS) array chip, whose basic sensing element is ion-sensitive field-effect transistor (ISFET) [28,29,30,31,32,33,34]
In this study, based on the semiconductor manufacturing international corporation (SMIC) 180 nm CMOS manufacturing process, the ISFET microarray sensor chip is used for pH measurement and DNA detection

Summary

Introduction

Deoxyribonucleic acid (DNA) sequencing [1,2], detection of the order of nucleotides in DNA strands, plays a significant role in the field of life and health. The core sensor detection and data processing capability of a semiconductor gene sequencer depends on a complementary metal-oxide semiconductor (CMOS) array chip, whose basic sensing element is ion-sensitive field-effect transistor (ISFET) [28,29,30,31,32,33,34]. Due to the ISFET’s sensitivity to hydrogen ions and compatibility with CMOS processes, it is possible to integrate large-scale sensor arrays on a single tiny chip to collect signals in a parallel, high-throughput way continuously. In this study, based on the semiconductor manufacturing international corporation (SMIC) 180 nm CMOS manufacturing process, the ISFET microarray sensor chip is used for pH measurement and DNA detection. The proposed high-density, COMS-compliant, low-cost ISFET array chip is of great significance for DNA detection and sequencing applications.

System Chip Design and Signal Readout Circuit Design

Sensor Chip Packaging

Electronic Performance

Electrolyte Flow Is Measured on the Sensor Chip Surface

PH Sensitivity Test and DNA Base Pairing Test

Conclusions