Towards Integrated Micro-Machined Silicon-Based Nanopores for Characterization of Dna

Chang, Hsien-Chih; Kosari, Farhad; Andreadakis, G.; Vasmatzis, George; Basgall, E. J.; King, Adrienne; Bashir, Rashid

doi:10.31438/trf.hh2004.55

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“…Recent reports of the use of ion milling 7 and transmission electron beam imaging , with real time feedback to form controlled pore size have paved the way to begin the exploration of single DNA molecule translocations and conformational studies using artificial pores. The electronic signature of dsDNA moving through these nanopores can be quite complex and the conformational changes in the molecule cannot be ignored, as shown recently by Li et al One possibility to suppress signatures due to conformational changes is to increase the entropic energy barrier for molecules to enter the nanopore by the use of “channels” with nanoscale diameters .…”

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“…The electronic signature of dsDNA moving through these nanopores can be quite complex and the conformational changes in the molecule cannot be ignored, as shown recently by Li et al One possibility to suppress signatures due to conformational changes is to increase the entropic energy barrier for molecules to enter the nanopore by the use of “channels” with nanoscale diameters . We fabricated 50−60 nm long, 4−5 nm diameter nanopore channels in micromachined silicon membranes . The nanopore channels were fabricated with a process similar to one described earlier 15 and commenced with double polished SOI wafers .…”

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“…We fabricated 50−60 nm long, 4−5 nm diameter nanopore channels in micromachined silicon membranes . The nanopore channels were fabricated with a process similar to one described earlier 15 and commenced with double polished SOI wafers . The buried oxide and SOI layers were 400 and 190 nm thick, respectively.…”

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DNA-Mediated Fluctuations in Ionic Current through Silicon Oxide Nanopore Channels

et al. 2004

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Single molecule sensors in which nanoscale pores within biological or artificial membranes act as mechanical gating elements are very promising devices for the rapid characterization and sequencing of nucleic acid molecules. The two terminal electrical measurements of translocation of polymers through single ion channels and that of ssDNA molecules through protein channels have been demonstrated, and have sparked tremendous interest in such single molecule sensors. The prevailing view regarding the nanopore sensors is that there exists no electrical interaction between the nanopore and the translocating molecule, and that all nanopore sensors reported to-date, whether biological or artificial, operate as a coulter-counter, i.e., the ionic current measured across the pore decreases (is mechanically blocked) when the DNA molecule transverses through the pore. We have fabricated nanopore "channel" sensors with a silicon oxide inner surface, and our results challenge the prevailing view of exclusive mechanical interaction during the translocation of dsDNA molecules through these channels. We demonstrate that the ionic current can actually increase due to electrical gating of surface current in the channel due to the charge on the DNA itself.As a first step toward the ultimate goal of single-molecule DNA sequencing using nanopore sensors, one must first identify the key mechanical and electrical variables that control the translocation of the molecules through the nanopores. First, a nanopore used for characterization and sequencing of a single molecule must have a diameter of less than the persistence length (∼50 nm for dsDNA) to avoid any signal averaging from thermally induced conformational changes. Second, the pores must be chemically stable and mechanically robust under a wide variety of conditions of use. Third, and finally, the mechanical and electrical interaction between the nanopores and the single molecules must be well characterized. Toward this end, the electrical detection of translocation of polymers through single ion channels has been demonstrated. 1-2 Subsequently, the pioneering studies of the use of R-hemolysin protein pore within a lipid bilayer for the translocation of single strands of DNA molecules using a voltage bias across the membranes sparked tremendous interest in such single molecule sensors. [3][4][5][6][7][8] The normal ionic current through the protein pore in a lipid bilayer would detectably reduce as a polyanionic chain of ssDNA molecules traversed through the pore, even allowing the distinction between polycytosine and polyadenine molecules, thus demonstrating the potential of single base discrimination in these sensors. 4,5 Despite these advantages, robust integration of these biological sensors within practical devices is quite problematic, and a mechanical pore 9,10 provides numerous advantages over biological pores. Besides the obvious advantages of being able to drastically change ambient conditions such as pH, electric field, and temperature without distorting the s...

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DNA-Mediated Fluctuations in Ionic Current through Silicon Oxide Nanopore Channels

et al. 2004

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“…However, their mechanism was completely different from Li's process. In this process, the e-beam locally fluidized the oxide around the pore, and hence oxide flowed towards the pore and then filled it (22). Figure 2 shows a final TEM image of a typical NPC (20).…”

Section: Solid-state Nanoporesmentioning

confidence: 99%

Silicon-Based Novel Bio-Sensing Platforms at the Micro and Nano Scale

Liu

Iqbal

2009

ECS Trans.

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Microfabrication traditionally has been limited to silicon as demonstrated by the multi-billion dollar industry. The field is now understandably developing into a combination of physics, chemistry and biology in very non-traditional approaches to develop functional devices.Some examples are on-chip hybridization of deoxyribonucleic acid (DNA) and optical detection, DNA/protein/cell detection at the micro scale for diagnostics in medical, military, and food safety applications, etc. One area where silicon based nanotechnology can have an immediate and far reaching impact is sensing biological molecules and their processes, especially in genomics and proteomics. The promise of nanofabrication lies in the special ability to fabricate devices not only down to the scales of bacteria and viruses, but even down to the scales of the smallest biological entities, such as DNA! Nanotechnology and BioMEMS will have a significant impact on medicine and biology in the areas of single cell detection, diagnosis and combating disease, providing specificity of drug delivery for therapy, and avoiding time consuming steps to provide faster results and solutions to the patient. Integration of biology and silicon at the micro and nano scale offers tremendous opportunities for solving important problems in biology and medicine and enables a wide range of applications in diagnostics, therapeutics, and tissue engineering. This paper reviews state of the art in silicon-based bioMEMS and bionanotechnology as well as the future challenges and opportunities. A range of silicon devices integrating microsystems engineering with biology are discussed with focus on rapid detection of biological entities and development of point of care devices using electrical or mechanical phenomena at the micro and nano scale.

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Solid-state nanopore channels with DNA selectivity

2007

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Solid-state nanopores have emerged as possible candidates for next-generation DNA sequencing devices. In such a device, the DNA sequence would be determined by measuring how the forces on the DNA molecules, and also the ion currents through the nanopore, change as the molecules pass through the nanopore. Unlike their biological counterparts, solid-state nanopores have the advantage that they can withstand a wide range of analyte solutions and environments. Here we report solid-state nanopore channels that are selective towards single-stranded DNA (ssDNA). Nanopores functionalized with a 'probe' of hair-pin loop DNA can, under an applied electrical field, selectively transport short lengths of 'target' ssDNA that are complementary to the probe. Even a single base mismatch between the probe and the target results in longer translocation pulses and a significantly reduced number of translocation events. Our single-molecule measurements allow us to measure separately the molecular flux and the pulse duration, providing a tool to gain fundamental insight into the channel-molecule interactions. The results can be explained in the conceptual framework of diffusive molecular transport with particle-channel interactions.

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Towards Integrated Micro-Machined Silicon-Based Nanopores for Characterization of Dna

Cited by 3 publications

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DNA-Mediated Fluctuations in Ionic Current through Silicon Oxide Nanopore Channels

DNA-Mediated Fluctuations in Ionic Current through Silicon Oxide Nanopore Channels

Silicon-Based Novel Bio-Sensing Platforms at the Micro and Nano Scale

Solid-state nanopore channels with DNA selectivity

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