Improving Signal To Noise Ratio And Time Resolution For Solid-State Nanopore Measurements

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Doctor of Philosophy (PhD)
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Physics & Astronomy
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CMOS amplifier
DNA sequencing
glass chip
low capacitance
solid-state nanopore
Physics
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2018-09-27T20:18:00-07:00
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Abstract

Nanopores have seen broad applicability as single-molecule sensors because of their spatiotemporally localized transduction and high intrinsic gain. In this dissertation, we seek to increase the bandwidths accessible to nanopore measurements through improvements to nanopores, associated measurements electronics, and their integration. Solid-state pores, in particular, can generate signals that are often more than an order of magnitude larger than their biological counterparts. These larger signals make solid-state pores much more amenable to high-bandwidth measurements. Earlier work showed DNA translocation measurements with sub-microsecond temporal resolution using silicon nitride nanopores. In this dissertation, we further improve the temporal resolution to 100 ns by a recently developed CMOS nanopore amplifier (CNP2) with 10 MHz bandwidth capacity using silicon nitride pores thinned with electronic beam techniques to < 3 nm thickness, with pore diameter compatible for ssDNA that hugs the molecules as it translocates. Overall signal-to-noise-ratio-limited bandwidth is optimized through appropriate choice of pore size, salt and bias voltage. To further reduce Cpore, we are passivating silicon-nitride pores with thick dielectrics. We have previously reported on fused-silica based solid state membrane carrying platform which allows us to reduce Cpore to values < 1 pF. We also make use of this versatile, low-capacitance platform to suspend other thin, two-dimensional membrane such as MoS2 to take advantage of the atomic thickness of these 2D materials to increase spatial resolution. In this dissertation, we present data of improvements in DNA translocation recordings in both time resolution and signal to noise ratio (SNR) from combining our custom electronics with these low-capacitance, high-conductance ultra-thin pores. The ultra-low measurement noise allows us to observe an excess current dependent noise due to the pore itself, and the rich dynamics as DNA translocate through the nanopore. We also explore other applications beyond single nanopore such as nanopore arrays and nanoribbon-nanopore devices.

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Marija Drndic
Eleni Katifori
Date of degree
2018-01-01
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