An integrated semiconductor device enabling non-optical genome sequencing (original) (raw)

A new era of semiconductor genetics using ion-sensitive field-effect transistors: the gene-sensitive integrated cell

Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 2014

Semiconductor genetics is now disrupting the field of healthcare owing to the rapid parallelization and scaling of DNA sensing using ion-sensitive field-effect transistors (ISFETs) fabricated using commercial complementary metal -oxide semiconductor technology. The enabling concept of DNA reaction monitoring introduced by Toumazou has made this a reality and we are now seeing relentless scaling with Moore's law ultimately achieving the $100 genome. In this paper, we present the next evolution of this technology through the creation of the gene-sensitive integrated cell (GSIC) for label-free real-time analysis based on ISFETs. This device is derived from the traditional metal-oxide semiconductor field-effect transistor (MOSFET) and has electrical performance identical to that of a MOSFET in a standard semiconductor process, yet is capable of incorporating DNA reaction chemistries for applications in single nucleotide polymorphism microarrays and DNA sequencing. Just as applicatio...

CMOS ISFET device for DNA Sequencing: Device Compensation, Application Requirements and Recommendations

Ion sensitive field-effect transistor in DNA sequencing application is gaining popularity because of its capability to work massive parallel sensor arrays, especially when integrated in CMOS technology fabrication with inherent scalability from silicon at low cost. This paper reviews methods used in the last decade to design different topologies of ISFET sensor array device for DNA sequencing. Non-idealities of CMOS ISFET device introduced and its compensation in terms of the device being more robust than the system. Application and design requirements of DNA sequencing based on ISFET have been extracted from the literature as a process flow for designers to use. Further, several recommendations mentioned as concluded from previous works that would be useful for future research. After the invention of ISFET by Bergveld, more review articles have been reported but not for specific applications. Hence, this paper will showcase the importance of ISFET application in terms of point-of-care diagnostics and may result in biosensors evolution.

High accuracy DNA sequencing on a small, scalable platform via electrical detection of single base incorporations

High throughput DNA sequencing technologies have undergone tremendous development over the past decade. Although optical detection-based sequencing has constituted the majority of data output, it requires a large capital investment and aggregation of samples to achieve optimal cost per sample. We have developed a novel electronic detection-based platform capable of accurately detecting single base incorporations. The GenapSys technology with its electronic detection modality allows the system to be compact, accessible, and affordable. We demonstrate the performance of the system by sequencing several different microbial genomes with varying GC content. The platform is capable of generating 1.5 Gb of high-quality nucleic acid sequence in a single run. We routinely generate sequence data that exceeds 99% raw accuracy with read lengths of up to 175 bp. The utility of the platform is highlighted by targeted sequencing of the human genome. We show high concordance of SNP detection on the...

A Digital CMOS DNA Chip

2005 IEEE International Symposium on Circuits and Systems

A fully electronic medium density DNA micro array is presented using a CMOS process extended by gold electrodes. The chip provides 128 sensor sites, in-sensor site current-mode A/D conversion, peripheral circuitry including bandgap and current references, D/A-converters to provide electrode bias voltages, calibration circuitry, and a 6 pin interface for power supply and serial digital data transfer. I.

A Fully Electronic Label-Free DNA Sensor Chip

IEEE Sensors Journal, 2000

This paper presents a microfabricated DNA chip for fully electronic, label-free DNA recognition based on capacitance measurements. The chip has been fabricated in 0.5-mum CMOS technology and it features an array of individually addressable sensing sites consisting of pairs of gold electrodes and addressing logic. Read-out circuitry is built externally using standard components to provide increased experimental flexibility. The chip

Development of an integrated CMOS DNA detection biochip

Sensors and Actuators B: Chemical, 2007

This paper presents a CMOS DNA detection biochip using an electrical detection method with self-assembly multilayer gold nanoparticles (AuNPs). Each measuring spot of this biochip consists of three major parts; a pair of electrodes with a nanogap, a current amplifier circuit, and a heater with an embedded temperature sensor. The biochip is first fabricated by a TSMC (Taiwan Semiconductor Manufacturing Company Ltd.) 0.35 m 2P4M standard CMOS process. Then, post-CMOS micromachining etch processes are used to expose the surface of the nanogap to test samples for the establishment of multilayer AuNPs through hybridization between single strand DNAs in the samples. The gap distance between a pair of electrodes is 350 nm. Before taking DNA detection measurements, self-assembly monolayer AuNPs is established on the nanogap surface between two microelectrodes. Multilayer AuNPs can be observed if hybridization between single strand DNAs occurs. An approximately 1000-fold increase in electric current between the multilayer AuNPs over the monolayer AuNPs serves an indication of the presence of target DNA in test samples. After integrating the electrodes with an embedded current amplifier, the electric current of multilayer AuNPs is amplified to the order of mA that can be easily measured by a commercial Volt-Ohm-Milliammeter. The heating system with a heating element and a temperature sensor can be used to distinguish single base-pair mismatch hybridization from complementary hybridization for the establishment of multilayer AuNPs. The lowest detectable concentration of target DNA on this biochip is 0.1 nM.

VLSI Structures for DNA Sequencing—A Survey

Bioengineering

DNA sequencing is a critical functionality in biomedical research, and technical advances that improve it have important implications for human health. Novel methods by which sequencing can be accomplished in more accurate, high-throughput, and faster ways are in development. Here, we review VLSI biosensors for nucleotide detection and DNA sequencing. Implementation strategies are discussed and split into function-specific architectures that are presented for reported design examples from the literature. Lastly, we briefly introduce a new approach to sequencing using Gate All-Around (GAA) nanowire Metal Oxide Semiconductor Field Effect Transistors (MOSFETs) that has significant implications for the field.

Optoelectronic DNA chip: high performance chip reading with an all-electric interface

Biosensors & Bioelectronics, 2005

Reading of DNA chips is usually based on fluorescence labeling of hybridised target molecules. Combined with the use of confocal fluorescence scanners, this approach shows very high performances in terms of accuracy and sensitivity. However, fluorescence readers remain costly and cumbersome. This prevents the use of DNA chips as a decentralised testing tool. Electrical monitoring of hybridisation is one way to reduce the cost and size of the reader. However, the multiplexing of electric detection-based systems in a miniaturised form remains challenging.