High-bandwidth DNA sequencing using graphene nanoribbon-nanopore devices

使用石墨烯纳米带-纳米孔装置进行高带宽 DNA 测序

• 批准号: 8755887
• 负责人: Marija Drndic
• 金额: $ 44万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8755887
• 关键词: Address; Amplifiers; Base Sequence; Caliber; Carbon; Cells; Charge; Custom; DNA; DNA Sequence; Detection; Development; Devices; Diagnosis; Discrimination; Electrolytes; Electronics; Electrostatics; Enzymes; Exhibits; Fiber Optics; Genetic; Geometry; Goals; Grant; Individual; Ion Channel; Lead; Length; Letters; Location; Measurement; Measures; Methods; Microscope; Motion; Noise; Nucleotides; Patients; Reading; Relative (related person); Reporting; Research; Resolution; Shapes; Side; Signal Transduction; Single-Stranded DNA; Sodium Chloride; Solutions; Speed; Symptoms; Techniques; Technology; Testing; Thick; Variant; Vision; Width; base; cost; density; design; disorder prevention; electrical property; nano; nanopore; nanoscale; next generation; prevent; public health relevance; screening; sensor; voltage

DESCRIPTION (provided by applicant): We propose to sequence DNA by harnessing the one-atom thickness (as thin as the separation between nucleotides) and electrical properties of graphene. A direct readout of the DNA sequence is possible by measuring the modulation of the current flowing through a single-layer graphene nanoribbon (GNR), induced by each base in a single-stranded DNA molecule as it passes through a nanopore (NP) in that GNR. This geometry is anticipated to exhibit large changes in the charge density and electrical current levels in the GNR for each nucleotide base translocating due to the unique electrostatic potential associated with each nucleotide. The major benefit of this approach is that the GNR operating currents (1-10 mA) are orders of magnitude higher than the signals in ionic-current-based sequencing, enabling much higher signal-to-noise ratio and sequencing speeds of 106 bases/s. Important feasibility tests have already been realized in our group. We tested 20 - 200 nm-wide single-layer GNRs with NPs at the GNR edges carrying up to 10 mA in 1 mM to 1M KCl solution at bandwidths as high as 100 MHz. We also developed a method to drill NPs without lowering the GNR conductance and observed correlated GNR and ionic signals during dsDNA translocation. We anticipate that single- base resolution will be achievable at currently reported DNA translocation speeds. This eliminates the need for custom high-speed ultralow noise electronics, as many off-the-shelf photodiode amplifiers for fiber-optics are designed for these current and bandwidth ranges. It also removes the need to slow down or constrain the DNA molecule as it translocates, since the measurement speed is high enough to prevent Brownian fluctuations of the molecule from blurring the GNR signal. The aims of our proposed research are as follows: 1. Optimize GNR device parameters and measurement conditions to achieve sequencing with an error rate less than 0.1% at 10 MHz bandwidth. 2. Demonstrate proof-of-principle multiplexing with ten GNRs on a single chip. 3. Develop the GNR nucleotide sensing mechanism towards an ultrafast, low cost DNA sequencing solution.

描述(由申请人提供)：我们建议通过利用石墨烯的单原子厚度(与核苷酸之间的距离一样薄)和电学性质来对DNA进行排序。直接读出DNA序列是可能的，方法是测量流经单层石墨烯纳米带(GNR)的电流的调制，当单链DNA分子通过该GNR中的纳米孔(NP)时，该电流由单链DNA分子中的每个碱基感应。由于与每个核苷酸相关的独特静电势，这一几何形状预计将显示出每个核苷酸碱基移位的GNR中的电荷密度和电流水平的巨大变化。这种方法的主要好处是，GNR工作电流(1-10 mA)比离子电流测序中的信号高出几个数量级，使信噪比和测序速度达到106base/S。我们测试了20-200 nm宽的单层GNR，在GNR边缘携带着高达10 mA的NPR，在1 mm到1M的KCl溶液中，带宽高达100 MHz。我们还开发了一种在不降低GNR电导的情况下钻探NPs的方法，并在dsDNA易位过程中观察到了相关的GNR和离子信号。我们预计，以目前报道的DNA易位速度，单碱基的分辨率是可以实现的。这消除了定制高速超低噪声电子设备的需求，因为许多现成的光纤光电二极管放大器都是为这些电流和带宽范围而设计的。它还消除了在DNA分子移位时减缓或限制DNA分子的需要，因为测量速度足够高，以防止分子的布朗波动模糊GNR信号。我们的研究目标如下：1.优化GNR器件参数和测量条件，在10 MHz带宽下实现误码率小于0.1%的定序。2.在一块芯片上演示10个GNR的原理证明多路复用。3.开发GNR核苷酸传感机制以实现超快、低成本的DNA测序解决方案。