A very large integrated pH-ISFET sensor array chip compatible with standard CMOS processes

Yeow, T.C.W.; Haskard, M.R.; Mulcahy, Dennis; Seo, Hee-Suk; Kwon, Daehan

doi:10.1016/s0925-4005(97)00207-4

Cited by 54 publications

(21 citation statements)

References 6 publications

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“…Although a variety of electrochemical detection methods have been studied 24,25 , the ion-sensitive field-effect transistor (ISFET) 26,27 was most applicable to our chemistry and scaling requirements because of its sensitivity to hydrogen ions, and its compatibility with CMOS processes [28][29][30][31] . Previous attempts to detect both single-nucleotide polymorphisms (SNPs) 32 and DNA synthesis 33 as well as sequence DNA electronically 34 have been made.…”

mentioning

confidence: 99%

An integrated semiconductor device enabling non-optical genome sequencing

Rothberg¹,

Hinz²,

Rearick³

et al. 2011

Nature

1,895

1,157

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The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.DNA sequencing and, more recently, massively parallel DNA sequencing 1-4 has had a profound impact on research and medicine. The reductions in cost and time for generating DNA sequence have resulted in a range of new sequencing applications in cancer 5,6 , human genetics 7 , infectious diseases 8 and the study of personal genomes 9-11 , as well as in fields as diverse as ecology 12,13 and the study of ancient DNA 14,15 . Although de novo sequencing costs have dropped substantially, there is a desire to continue to drop the cost of sequencing at an exponential rate consistent with the semiconductor industry's Moore's Law 16 as well as to provide lower cost, faster and more portable devices. This has been operationalized by the desire to reach the $1,000 genome 17 .To date, DNA sequencing has been limited by its requirement for imaging technology, electromagnetic intermediates (either X-rays 18 , or light 19 ) and specialized nucleotides or other reagents 20 . To overcome these limitations and further democratize the practice of sequencing, a paradigm shift based on non-optical sequencing on newly developed integrated circuits was pursued. Owing to its scalability and its low power requirement, CMOS processes are dominant in modern integrated circuit manufacturing 21 . The ubiquitous nature of computers, digital cameras and mobile phones has been made possible by the low-cost production of integrated circuits in CMOS.Leveraging advances in the imaging field-which has produced large, fast arrays for photonic imaging 22 -we sought a suitable electronic sensor for the construction of an integrated circuit to detect the hydrogen ions that would be released by DNA polymerase 23 during sequencing by synthesis, as opposed to a sensor designed for the detection of photons. Although a variety ...

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mentioning

confidence: 99%

An integrated semiconductor device enabling non-optical genome sequencing

Rothberg¹,

Hinz²,

Rearick³

et al. 2011

Nature

1,895

1,157

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“…However, research is continuing to overcome these problems. Many designs have been suggested for EnFET biosensors [76,77,78,79,80,81,82,83], as well as other forms of FET-based biosensors (e.g. ImmunoFET, GenFET, cell-based FET, etc.…”

Section: Field-effect Transistor (Fet)mentioning

confidence: 99%

Electrochemical Biosensors - Sensor Principles and Architectures

Grieshaber

MacKenzie

Vörös

et al. 2008

Sensors

855

636

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Quantification of biological or biochemical processes are of utmost importance for medical, biological and biotechnological applications. However, converting the biological information to an easily processed electronic signal is challenging due to the complexity of connecting an electronic device directly to a biological environment. Electrochemical biosensors provide an attractive means to analyze the content of a biological sample due to the direct conversion of a biological event to an electronic signal. Over the past decades several sensing concepts and related devices have been developed. In this review, the most common traditional techniques, such as cyclic voltammetry, chronoamperometry, chronopotentiometry, impedance spectroscopy, and various field-effect transistor based methods are presented along with selected promising novel approaches, such as nanowire or magnetic nanoparticle-based biosensing. Additional measurement techniques, which have been shown useful in combination with electrochemical detection, are also summarized, such as the electrochemical versions of surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz crystal microbalance, and scanning probe microscopy. The signal transduction and the general performance of electrochemical sensors are often determined by the surface architectures that connect the sensing element to the biological sample at the nanometer scale. The most common surface modification techniques, the various electrochemical transduction mechanisms, and the choice of the recognition receptor molecules all influence the ultimate sensitivity of the sensor. New nanotechnology-based approaches, such as the use of engineered ion-channels in lipid bilayers, the encapsulation of enzymes into vesicles, polymersomes, or polyelectrolyte capsules provide additional possibilities for signal amplification. In particular, this review highlights the importance of the precise control over the delicate interplay between surface nano-architectures, surface functionalization and the chosen sensor transducer principle, as well as the usefulness of complementary characterization tools to interpret and to optimize the sensor response.

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“…Later a very large pH-ISFET sensor array of 240 devices was reported [35]. In large sensor arrays the number of connection pads required to address individual sensors is inconveniently high and some multiplexing circuitry becomes necessary.…”

Section: Integrated Sensor Arraysmentioning

confidence: 99%