Low Cost Sequencing with Re-usable Magnetic Arrays and Nanoelectronic Sensors

利用可重复使用的磁性阵列和纳米电子传感器进行低成本测序

• 批准号: 8545206
• 负责人: HESAAME Esfandyarpour
• 金额: $ 103.46万
• 依托单位: GENAPSYS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-14 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545206
• 关键词: Arts; Automation; Biology; Cataloging; Catalogs; Charge; Clinical; Consumption; Containment; Cost Savings; DNA; DNA Sequence; DNA amplification; Data; Detection; Development; Devices; Diagnostic; Dideoxy Chain Termination DNA Sequencing; Disease Management; Electronics; Emulsions; Generations; Genes; Genome; Genomics; Goals; Health; Healthcare; Human; Individual; Label; Length; Ligation; Magnetism; Mainstreaming; Mediating; Medical; Medical Research; Medicine; Methods; Nucleotides; Optics; Output; Performance; Phase; Poisson Distribution; Polymerase; Preparation; Price; Process; Reaction; Reading; Reagent; Relative (related person); Research; Running; Sampling; Signal Transduction; Societies; Sorting - Cell Movement; Source; Structure; System; Techniques; Technology; Testing; Time; base; biological research; cost; cost effective; density; electric field; electric impedance; genome sequencing; improved; innovative technologies; insight; instrument; nano; nanoelectronics; nanomagnetic; nanosensors; novel; price lists; sensor; single molecule; usability; virtual

Sequencing methods allowing cost effective and accurate de novo and re-sequencing genomes are critical to provide needed insights for human health, disease management and diagnostics at the individual level. Costs still remain too high with inadequate quality, to make sequencing technologies affordable for the routine use of genomics in individual health care. The "Gene Electronic Nano-Integrated Ultra-Sensitive" (GENIUS) platform is based on innovative technologies to provide significant improvements in cost, accuracy, read length, throughput and ease of use relative to current state-of-art systems. The overall goal is to develop a sequencing system using nano-magnetic-electronic platforms. We are proposing a system that integrates sample preparation and enrichment steps with the sequencing module. Sample preparation will rely on a re-usable magnetic-electronic chip and a novel emulsion-free amplification method. After amplification, enrichment of template carrying monoclonal beads is achieved through 'sorting' based on DNA charge. Beads are then transferred and held on a micromagnet array integrated with a sequencing sensor chip consisting of high-density arrays of CMOS-based nano-electronic sensors for direct detection of extension reactions. In lieu of a reverse emulsion we are developing an easy to use, chip-based approach that will combine multiple sample processing steps in a single device. The purpose of the 'Virtual Nano-Reactor' chip is to generate clonal amplified template on high-density array of single beads. The efficient capture of beads, concentration and confinement of DNA and amplification products, may permit the elimination of whole genome amplification with its inherent bias. The re-usable 'Virtual Nano-reactor' chip provides uniform reaction conditions across the entire chip. The device will eliminate the variability in reaction volumes and double-Poisson distribution inherent in emulsion PCR. The re-usable "well-free" sequencing sensor chip provides high-sensitivity detection, efficient and uniform reagent delivery and washing, combined with the high efficiency bead capture and permits longer reads and higher accuracy by minimizing de-phasing and providing uniformity of reaction, and also reduce reagent consumption and cost. The re-usability of the chip significantly reduces the consumable cost. In summary, the simplified automatable workflow with low reagent consumption, label-free electronic detection using unmodified nucleotides and polymerase results in significant cost savings and improved accuracy. Our goal is to develop a platform to sequence a genome with consumable costs of ~$50, average read length of up to 1000 bases, and pre-assembly accuracy of > 99.7% with similar cost reduction and simplification for sample preparation.

测序方法允许成本效益和准确的从头和重新测序基因组是至关重要的