Study of the electrolyte-insulator-semiconductor field-effect transistor (EISFET) with applications in biosensor design

Abstract

This paper presents a comprehensive review of the ion-sensitive field-effect transistor (ISFET) and its applications in biomolecular sensing and characterization of electrochemical interfaces. An introduction to the physics of field-effect transistors is presented, followed by a study of the properties of electrolytic solutions and electrolyte interface surface effects. Full modeling of the ion-sensitive transistor is given, followed by a survey of the different uses of the ISFET in biomedical and environmental applications. Particular attention is given to the use of the ion-sensitive transistors as replacements for microarrays in DNA gene expression analysis.

Introduction

Current trends in health science and biomedical research indicate a continuous need for technologies that allow for the achievement of accurate measurements and consistent results [1], [2], [3]. Given the stochastic nature of the experiments studied in the biomedical realm, it is necessary to eliminate errors and inconsistencies that arise from poorly prepared environments. Generally, discrepancies in biomedical experiments come as results of secondary reactions or unwanted side-effects, many of which could be avoided in more controlled environments or using highly purified experimental chambers [1]. During the past few decades, advances in device fabrication technology has enabled a high degree of control over fabrication processes, allowing for high levels of integration and very predictable device performance characteristics [4], [5]. This shared interest in quality of experiment suggests the need to study means of integrating semiconductor fabrication technology with biological and chemical environments to achieve better experimental outcomes in health science and biomedical applications.

Most chemical and biomedical tests and experiments are conducted inside laboratories with a large number of expensive equipment [3], [6], [7], [8]. It is therefore very difficult to conduct environmental or medical tests in rural areas. The specimen to be tested would have to be transported to a lab that has the required equipment, which could be geographically distant. In many cases, the specimen must be preserved under specific environmental conditions while being transported and the possibility of sample deterioration or contamination always exists [9]. These difficulties can be overcome if such experiments could be conducted using small, inexpensive, easy-to-use portable devices. The semiconductor industry allows for the integration of many advanced instrumentation and analysis circuits in a relatively small area [10]. Therefore, if one can combine the chemical or biological medium with that of the semiconductor and integrated circuit, then the idea of an integrated analysis chip would be a reality. Biochemical sensors could then be integrated with semiconductors and inexpensive, miniature “labs” could then be realized in small devices.

Many biochemical experiments use large quantities of analyte samples, catalysts, and detectors. This is done for many reasons, the most important of which are the limited sensitivity of many detection schemes, and the limited amount of control over the dynamics of the experiments [3]. The large quantities result in the need for sophisticated equipment for data analysis and complicated algorithms for interpretation [9]. If such experiments could be conducted with extremely small quantities of reactants, one would expect more correlated results, less complex equipment for sensing, and possibly less time for conducting the experiment. However, constructing biochemical sensors for small quantities of reactants requires a large degree of sensitivity. Field-effect devices, fabricated using semiconductor technology, provide excellent candidates for constructing such sensors, due to the high level of purity in the design [4], and the extremely small dimensions that can be used [8], all of which enhance the potential sensitivity of the device. Therefore, the idea of integrating the biochemical domain to that of microelectronics and integrated circuits seems quite appealing.

Much research has been devoted to realizing a device that would couple chemical and biological media with semiconductor integrated circuits [1], [6], [7], [11], [12], [13]. In this paper, one of these devices, the electrolyte–insulator–semiconductor field-effect transistor (EISFET), is presented. The EISFET provides means of detecting various biological and chemical processes by charge coupling. This coupling allows for electrical recording of biomolecular activities that occur in the vicinity of the EISFET [1]. Such sensors can be used extensively for monitoring chemical and biological contaminations, studying molecular interactions, and gene expression analysis.

In this review, first, a physical analysis of a traditional field-effect transistor is presented. After that, characterization of electrochemical surface bulk and processes will be presented, followed by an analysis of the EISFET structure. Then, the use of the EISFET as a biochemical sensor will be studied, and a thorough analysis of using the EISFET as a DNA hybridization sensor will be given. Finally, a comparison between current optical microarray technology and the upcoming EISFET-based microarrays will be presented.