1,548 research outputs found

    Embedded CMOS Basecalling for Nanopore DNA Sequencing

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    DNA sequencing is undergoing a profound evolution into a mobile technology. Unfortunately the effort needed to process the data emerging from this new sequencing technology requires a compute power only available to traditional desktop or cloud-based machines. To empower the full potential of portable DNA solutions a means of efficiently carrying out their computing needs in an embedded format will certainly be required. This thesis presents the design of a custom fixed-point VLSI hardware implementation of an HMM-based multi-channel DNA sequence processor. A 4096 state (6-mer nanopore sensor) basecalling architecture is designed in a 32-nm CMOS technology with the ability to process 1 million DNA base pairs per second per channel. Over a 100 mm^2 silicon footprint the design could process the equivalent of one human genome every 30 seconds at a power consumption of around 5 W

    Hardware Accelerated DNA Sequencing

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    DNA sequencing technology is quickly evolving. The latest developments ex- ploit nanopore sensing and microelectronics to realize real-time, hand-held devices. A critical limitation in these portable sequencing machines is the requirement of powerful data processing consoles, a need incompatible with portability and wide deployment. This thesis proposes a rst step towards addressing this problem, the construction of specialized computing modules { hardware accelerators { that can execute the required computations in real-time, within a small footprint, and at a fraction of the power needed by conventional computers. Such a hardware accel- erator, in FPGA form, is introduced and optimized specically for the basecalling function of the DNA sequencing pipeline. Key basecalling computations are identi- ed and ported to custom FPGA hardware. Remaining basecalling operations are maintained in a traditional CPU which maintains constant communications with its FPGA accelerator over the PCIe bus. Measured results demonstrated a 137X basecalling speed improvement over CPU-only methods while consuming 17X less power than a CPU-only method

    A novel, fast, HMM-with-Duration implementation – for application with a new, pattern recognition informed, nanopore detector

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    <p>Abstract</p> <p>Background</p> <p>Hidden Markov Models (HMMs) provide an excellent means for structure identification and feature extraction on stochastic sequential data. An HMM-with-Duration (HMMwD) is an HMM that can also exactly model the hidden-label length (recurrence) distributions – while the regular HMM will impose a best-fit geometric distribution in its modeling/representation.</p> <p>Results</p> <p>A Novel, Fast, HMM-with-Duration (HMMwD) Implementation is presented, and experimental results are shown that demonstrate its performance on two-state synthetic data designed to model Nanopore Detector Data. The HMMwD experimental results are compared to (i) the ideal model and to (ii) the conventional HMM. Its accuracy is clearly an improvement over the standard HMM, and matches that of the ideal solution in many cases where the standard HMM does not. Computationally, the new HMMwD has all the speed advantages of the conventional (simpler) HMM implementation. In preliminary work shown here, HMM feature extraction is then used to establish the first pattern recognition-informed (PRI) sampling control of a Nanopore Detector Device (on a "live" data-stream).</p> <p>Conclusion</p> <p>The improved accuracy of the new HMMwD implementation, at the same order of computational cost as the standard HMM, is an important augmentation for applications in gene structure identification and channel current analysis, especially PRI sampling control, for example, where speed is essential. The PRI experiment was designed to inherit the high accuracy of the well characterized and distinctive blockades of the DNA hairpin molecules used as controls (or blockade "test-probes"). For this test set, the accuracy inherited is 99.9%.</p

    The NTD Nanoscope: potential applications and implementations

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    <p>Abstract</p> <p>Background</p> <p>Nanopore transduction detection (NTD) offers prospects for a number of highly sensitive and discriminative applications, including: (i) single nucleotide polymorphism (SNP) detection; (ii) targeted DNA re-sequencing; (iii) protein isoform assaying; and (iv) biosensing via antibody or aptamer coupled molecules. Nanopore event transduction involves single-molecule biophysics, engineered information flows, and nanopore cheminformatics. The NTD Nanoscope has seen limited use in the scientific community, however, due to lack of information about potential applications, and lack of availability for the device itself. Meta Logos Inc. is developing both pre-packaged device platforms and component-level (unassembled) kit platforms (the latter described here). In both cases a lipid bi-layer workstation is first established, then augmentations and operational protocols are provided to have a nanopore transduction detector. In this paper we provide an overview of the NTD Nanoscope applications and implementations. The NTD Nanoscope Kit, in particular, is a component-level reproduction of the standard NTD device used in previous research papers.</p> <p>Results</p> <p>The NTD Nanoscope method is shown to functionalize a single nanopore with a channel current modulator that is designed to transduce events, such as binding to a specific target. To expedite set-up in new lab settings, the calibration and troubleshooting for the NTD Nanoscope kit components and signal processing software, the NTD Nanoscope Kit, is designed to include a set of test buffers and control molecules based on experiments described in previous NTD papers (the model systems briefly described in what follows). The description of the Server-interfacing for advanced signal processing support is also briefly mentioned.</p> <p>Conclusions</p> <p>SNP assaying, SNP discovery, DNA sequencing and RNA-seq methods are typically limited by the accuracy of the error rate of the enzymes involved, such as methods involving the polymerase chain reaction (PCR) enzyme. The NTD Nanoscope offers a means to obtain higher accuracy as it is a single-molecule method that does not inherently involve use of enzymes, using a functionalized nanopore instead.</p

    Explosive Formation and Dynamics of Vapor Nanobubbles around a Continuously Heated Gold Nanosphere

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    We form sub-micrometer-sized vapor bubbles around a single laser heating gold nanoparticle in a liquid and monitor them through optical scattering of a probe laser. The fast, inertia-governed expansion is followed by a slower contraction and disappearance after some tens of nanoseconds. In a narrow range of illumination powers, bubble time traces show a clear echo signature. We attribute it to sound waves released upon the initial explosion and reflected by flat interfaces, hundreds of microns away from the particle. Echoes can trigger new explosions. A steady state of nanobubble with a vapor shell surrounding the heated nanoparticle can be reached by a proper time profile of the heating intensity. Stable nanobubbles could have original applications for light modulation and for enhanced optical-acoustic coupling in photoacoustic microscopy

    Nanopore Detector Feedback Control Using Cheminformatics Methods Integrated with Labview/Labwindows Tools

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    Single biopolymers (DNA, RNA, or polypeptide) can be examined using an alpha-hemolysin channel detector. When a biopolymer is present in an alpha-hemolysin channel it can produce a highly structured ionic current blockade pattern, where the lifetimes at various sub-blockade levels reveal information about the kinetics of the biopolymer. Here we describe integration of LabVIEW/LabWindows automation capabilities with the in-house Channel Current Cheminformatics (CCC) software. Data acquired with LabVIEW/LabWindows is passed to the CCC software, on a streaming real time basis, for analysis and classification. The classification results are then quickly returned to the LabVIEW/LabWindows automation software for experimental feedback control. The prototype signal processing architecture is designed to rapidly extract useful information from noisy blockade signals. A fast, specially designed, generic Hidden Markov Model can be used for the channel current feature extraction. Classification of feature vectors obtained by the HMM can then be done by Support Vector Machines

    The Potential and Challenges of Nanopore Sequencing

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    A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of ‘third generation’ instruments that will sequence a diploid mammalian genome for ~$1,000 in ~24 h.Molecular and Cellular BiologyPhysic
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