Alexandria Digital Research Library

Towards a CMOS integrated biological nanopore DNA sequencer

Morton, Danielle Marie
Degree Grantor:
University of California, Santa Barbara. Electrical & Computer Engineering
Degree Supervisor:
Luke Theogarajan
Place of Publication:
[Santa Barbara, Calif.]
University of California, Santa Barbara
Creation Date:
Issued Date:
Electrical engineering
DNA sequencing
Flicker noise
Dissertations, Academic and Online resources
Ph.D.--University of California, Santa Barbara, 2016

Improved DNA sequencing techniques have been a significant source of study over the past several decades. Efforts have mainly focused on increasing the speed, reducing the size, and improving the reproducibility to make the benefits more accessible to the general population while still producing highly accurate results. This thesis discusses the development of a several techniques required to design high speed, accurate sequencing array platforms in a small footprint. First, the thesis addresses the development of a more stable biological DNA sequencing platform by using a cutting-edge genetically-engineered protein (Mycobacterium smegmatis) MspA in highly stable, highly reproducible, triblock copolymer membranes tailored to reduce flicker noise to levels equal to the native unstable lipid membranes. The platform reproducibility is also improved through studies and optimization of voltage-enhanced single protein insertion technique, reducing the deleterious effects of the stochastic multi-protein insertion process. Second, the thesis introduces and implements a new opamp using a pseudo-switched biasing technique and only four transistors instead of the traditional seven in a standard two-stage opamp to conserve area (100 X 80 microm2) without sacrificing the accuracy requirements (~20 muV/√Hz ). The new amplifier also allows extended common-mode range input and near rail-to-rail output swing, ideal for use in individual control of an array. After silicon verification in IBM 130 nm technology in both the electronic testing and the nanopore testing lab, the new design is then used in the full design of a 12 X 12 array of integrate-sample biosensors in 4 X 4 mm2 die. The overall area of each sensor is 200 X 200 microm2 and has optional DC cancellation to improve the dynamic range of the electronic interface.

With the improved membrane stability, a more reliable protein insertion technique, and a compact biosensor array on a single chip, a more reliable, affordable DNA sequencing platform is not only possible, but highly probable within the next several years.

Physical Description:
1 online resource (183 pages)
UCSB electronic theses and dissertations
Catalog System Number:
Inc.icon only.dark In Copyright
Copyright Holder:
Danielle Morton
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