# Single Cell Chemotactic Responses of
## 1 Introduction  
_Helicobacter pylori_ (_H. pylori_) is a common bacterium that was first identified in 1983 [1]. _H. pylori_ cells are adapted to live in the harsh, acidic environment of the stomach and their spiral shape allows them to penetrate the stomach lining. _H. pylori_ colonizes the stomachs of approximately 50% of the human population and contributes to overt gastric disease, peptic inflammation, and ulceration. _H. pylori_ also have an etiological relationship with gastric cancer [2]; there is a gut microbe-host relationship that exists between _H. pylori_ and the human or animal gut. The ability of _H. pylori_ to interact with cells within the gastric epithelium is greatly influenced by its motility [3, 4]. In practice, first-line therapies fail 10%-20% of the time [5, 6], in part due to antibiotic resistance and poor compliance with complicated dosing schedules [7]. Motility in _H. pylori_ is essential for initiating and maintaining infections in humans and animal models [8]. Therefore, motility is a major virulence factor, and studies have reported that non-motile _H. pylori_ cells are less virulent [9]. Therefore, chemicals that modulate motility play an important role in virulence and are able to affect the severity of symptoms during _H. pylori_ infection [9]. _H. pylori_ cells utilize multiple flagella to move through the gastric environment, a process which is governed by chemotaxis (typically towards areas of lower pH) [10, 11]. Chemotaxis is defined as the preferential movement towards more favorable chemical environments. In the growth cycle of _H. pylori_ within the gastric mucosal layer, chemotaxis-directed motility is a remarkable characteristic [9]. Chemotaxis helps _H. pylori_ to establish and maintain infection in animal models [10]. Although a significant amount of work has been done to measure chemotaxisand general motility in _H. pylori_, there is no consensus on how these processes work during infection. For example, [PERSON] and [PERSON] [9] and [PERSON] _et al._[12] used very similar experimental methods, but obtained opposite findings in regards to the response of _H. pylori_ to aspartate. Using _in vivo_ models, [PERSON] _et al._[13] demonstrated that _H. pylori_ uses chemotaxis to guide itself to the stomach epithelium. Many other studies have assessed the response of _H. pylori_ to gradients of physiologically relevant compounds _in vitro_[14; 15]. However, the experimental conditions in those studies do not accurately mimic the conditions present _in vivo_. In particular, these models do not incorporate a viscoelastic medium or pH gradient, which are important environmental conditions relevant to infection [16]. It has been demonstrated that the pathogenic mechanisms of _H. pylori_ are influenced by urea. Urease activity allows _H. pylori_ cells to survive in an acidic gastric environment by creating a \"cloud\" of ammonia around the bacterium that helps to neutralize the pH of the surrounding environment, thus playing an important role in virulence and pathogenesis of gastric and peptic ulcers; ammonia generation leads to the destruction of the gastric epithelium [17; 18]. Furthermore, studies show that cytoplasmic urease plays a critical role in the chemotactic behaviors of _H. pylori_[19; 20]. Traditionally, microbes have been studied in the laboratory as cultures of isolated species using conventional microbiological techniques, in part due to the complexities involved in designing and building physiologically relevant environments. Microfluidics overcomes the limitations of traditional methods, and offers techniques for cultivating and investigating microbes in a more clinically realistic and physiologically relevant environment. Microfluidic devices have been become powerful tools used in cell biology applications, including cell culture [21] and handling and analysis [22; 23].