A Portable Readout System for Biomarker Detection with Aptamer-Modified CMOS ISFET Array
Dmitriy RyazantsevMark ShustinskiyAndrey SheshilAlexey TitovVitaliy GrudtsovValerii VechorkoIrakli KitiashviliKirill PuchninAlexander KuznetsovН. В. Комарова
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Abstract:
Biosensors based on ion-sensitive field effect transistors (ISFETs) combined with aptamers offer a promising and convenient solution for point-of-care testing applications due to the ability for fast and label-free detection of a wide range of biomarkers. Mobile and easy-to-use readout devices for the ISFET aptasensors would contribute to further development of the field. In this paper, the development of a portable PC-controlled device for detecting aptamer-target interactions using ISFETs is described. The device assembly allows selective modification of individual ISFETs with different oligonucleotides. Ta2O5-gated ISFET structures were optimized to minimize trapped charge and capacitive attenuation. Integrated CMOS readout circuits with linear transfer function were used to minimize the distortion of the original ISFET signal. An external analog signal digitizer with constant voltage and superimposed high-frequency sine wave reference voltage capabilities was designed to increase sensitivity when reading ISFET signals. The device performance was demonstrated with the aptamer-driven detection of troponin I in both reference voltage setting modes. The sine wave reference voltage measurement method reduced the level of drift over time and enabled a lowering of the minimum detectable analyte concentration. In this mode (constant voltage 2.4 V and 10 kHz 0.1Vp-p), the device allowed the detection of troponin I with a limit of detection of 3.27 ng/mL. Discrimination of acute myocardial infarction was demonstrated with the developed device. The ISFET device provides a platform for the multiplexed detection of different biomarkers in point-of-care testing.Keywords:
ISFET
Aptamer
SIGNAL (programming language)
Sine wave
金属酸化物半導体(MOS)電界効果トランジスターの原理を利用したion sensitive field effect transistor (ISFET)を試作した.このISFETは,MOS電界効果トランジスターと類似の構造をしているが,ゲート金属の代わりに,酸化タンタルの薄膜がイオン選択性膜として存在している.ISFETを溶液に浸すと,溶液と酸化タンタルとの間に発生する界面電位によってドレイン電流が変化する.この電流値によってpH濃度を測定することができる.その感度を1pH当たりの電位変化に換算すると約56mVであった.又,応答速度も非常に大きく数秒以内で安定となり,再現性もよくアルカリ誤差もほとんど生じなかった.
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In this paper we describe the temperature dependence of buried channel (BC) ion sensitive field effect transistor (ISFET). The device response depends on the temperature; hence, temperature variations can cause erroneous readings. A theoretical model describing the temperature dependence of BC-ISFET and a theoretical solution to eliminate the signal variations due to temperature changes are presented here. The suggested solution is based on an inverter containing n-BC-ISFET and p-BC-ISFET. The influence of various parameters on the operation of the inverter and its sensitivity are investigated. We discuss the influence of self-assembled monolayers on the operation of the inverter.
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In this paper we present the research results of influence of substrate potential in ion-selective field-effect transistors (ISFET) on output signal of chemical sensors, e.g. PH-meters. It is shown that the instability of substrate-source p-n junction bias in well-known chemical sensors, which use grounded reference electrode - ISFET gate, affect on sensor characteristics in negative way. The analytical description and research results of 'substrate effect' on ISFET characteristics are considered.
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The principle and operation of an ion-sensitive field effect transistor (ISFET) are summarized briefly, and the application of the device to development of biosensors is described. Several kinds of techniques are discussed to immobilize ionophores and enzymes on the ISFET.
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ISFET (ion sensitive field effect transistor)는 용액 중의 각종 이온 농도를 측정하는 반도체 이온 센서이다. ISFET는 작은 소자 크기, 견고한 구조, 즉각적인 반응속도, 기존의 CMOS공정과 호환이 가능하다는 장점이 있다. ISFET의 기본 구조는 기존의 MOSFET (metal oxide semiconductor field effect transistor)에서...
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An FET sensor is an integrated device of the insulated gate field effect transistor (IGFET) and the chemical sensor and therefore is named as chemically sensitive field effect transistor (CHEMFET). In the CHEMIFET, the gate metal is replaced a more complex structure having chemically sensitive layer. CHEMFETs are new type of chemical sensors and have potential advantages over conventional chemical sensors in miniatuarization, robust solid state nature, mass productivity etc. According to the nature of the interaction between the species to be detected and the chemically sensitive layer, CHEMFETs can be divided into two groups : one that will measure gas concentrations, for example Pd gate FET (H2 gas sensor) and the other that will measure ion concentrations in the solution. The latter called an ion sensitive FET (ISFET). This paper describes the present status of ISFET, that is, its histoical survey, principle, fabrication method and ion selectivities.
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