Publication Date

Fall 2019

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemical and Materials Engineering

Advisor

Anand K. Ramasubramanian

Keywords

High-Throughput Screening, lab on a chip, Metagenomics

Subject Areas

Chemical engineering

Abstract

The growing prevalence of antibiotic resistance is one of the greatest challenges facing humankind today. The Centers for Disease Control and Prevention (CDC) have estimated that about 2 million people in the US each year develop an infection caused by antibiotic-resistant bacteria, and about 23,000 people die. To combat this growing crisis, efforts geared toward the discovery of novel compounds, such as antimicrobial peptides (AMPs), have spurred. However, current approaches for identification of such compounds have proven to be costly, time-consuming and ineffective. This problem underscores the need for a new approach, one that is fundamentally different from traditional methods both in the content of the library being screened and in the screening methodology. As a first demonstration of this approach, we have developed an E. coli chip – a novel, robust, high-density nano-culture platform – and an associated high-throughput screening methodology to successfully screen for cells containing genes that confer resistance to ampicillin from a soil metagenomic library. This platform offers several advantages over the current industry standard, a 96-well microplate platform, including miniaturization, automation, reduced amount and cost of reagents and process time. It eliminates the need for more than one round of screening thus potentially speeding up the antibiotic discovery process. Further, a single E. coli chip can replace the work of approximately seven 96-well plates. These advantages make this technology ideal for further applications, including screening for AMPs.

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