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From Proteins to Protons: Design of Nanoscopic Conductive Polymers Biosensors for Point-of-care Diagnostics

Abstract

Conductive polymers are often used in biosensing architectures of many kinds. Their biocompatibility, electrical conductivity, and ease of polymerization allows many routes to fabricate innovative, nanoscale biosensors for point-of-care diagnostic purposes. The focus of this dissertation will be on two different types of nanoscale, conductive polymer biosensors that were fabricated since 2018 in the Penner Lab by myself and my associates. The first device is the Virus BioResistor (VBR). This device employs poly(3,4-ethylenedioxythiophene) (PEDOT) which is electropolymerized in the presence of virus particles which have been genetically engineered to bind a specific protein. A baselayer of PEDOT:PSS is used as a target for this electrodeposition. This event produces an electrically conductive bioaffinity layer, through which impedance measurements can be taken. In Chapter 2, advances are made to this device by increasing the PEDOT:PSS baselayer are discussed. The increase in the baselayer resistance causes a ~4x signal enhancement, without sacrificing signal-to-noise or specificity. The resulting device can detect deglycase 1 (DJ-1), a bladder cancer biomarker, at 10 pM in ~30 s. Chapter 3 discusses further enhancements made to the VBR through over-oxidation. The process of over-oxidation allows for the detection of larger proteins and antibodies, up to 150 kDa. Without this process, the VBR is insensitive to proteins larger than 66.5 kDa. This process has been shown to enable detection of multiple antibodies. Following this work, an effort was made to engineer a conductive polymer sensor that is nanoscopic in 3 dimensions, compared to the VBR which is only nanoscopic in 1 dimension. This device is discussed in Chapter 4 and is called a Nanojunction pH sensor (NJ-pH). The NJ-pH sensor relies on lithographically patterned nanowire electrodeposition to fabricated single gold nanowires onto which electrical contacts are evaporated. A nanogap is formed in this nanowire through electromigration, and the gap is then bridged through electropolymerization of poly(aniline) (PANI) which has a resistance that is pH sensitive. This device is shown to have impedances that range 5 orders of magnitude between pH 1 – 9, and can give a reliable pH measurement within 30 s. This device is completely nanoscopic and offers a new avenue for monitoring local pH on the nanoscale.

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