**1. Introduction**

Traditionally the process of mechanical homogenization has been employed in the laboratory setting for the disruption of animal or plant tissues in preparation for downstream molecular applications [1]. However, in the face of a global pandemic this technology has been adapted to increase efficacy and efficiency in viral detection in a variety of COVID-19 diagnostic workflows [2–4].

As the global community began to respond to the spread of SARS-CoV-2, the expansion of public health surveillance programs and community testing protocols became critical objectives [5]. However, the need for rapid expansion in testing capacity caused a tremendous strain on the supply chains providing the equipment and reagents traditionally needed for respiratory virus PCR-based testing [6]. As in most cases, necessity drove innovation. Given the large number of research and academic laboratories equipped to assist in PCR testing, many groups began to offer their assistance in processing patient samples while others began examining novel approaches to viral detection which circumvented the supply chain bottle

necks. During the development of these novel testing protocols laboratory safety, diagnostic assay sensitivity and specificity became top priority [5–7]. In an attempt to utilize common laboratory equipment to safely speed up testing efforts, the use of mechanical homogenization was proposed to inactivate the SARS-CoV-2 from nasopharyngeal swabs as a method of increasing safety during processing [2–4, 8].

In brief, mechanical homogenization is the process of using shearing forces applied via mechanical grinding media and rigorous repetitive motion to dissociates a given sample [1]. The parameters at which a sample is processed will impact the degree to which it is dissociated and the quality of the targeted product for downstream applications [1]. In the case of SARS-CoV-2, the goal of mechanical homogenization was to disrupt the viral envelope while still maintaining the integrity of its RNA [2, 3]. This allowed for a reduction in infective potential in the laboratory setting, while preserving the accuracy of polymerase chain reaction (PCR) based diagnostic assays [2, 3].

Following the initial application of mechanical homogenization to COVID-19 swab-based PCR protocols, this technology was adapted to process saliva samples for both antigen and PCR detection workflows [2–4]. Through mechanical homogenization, high viscosity saliva samples were sufficiently processed to allow for automation integration, paving the way for the widespread application of this novel methodology [4, 9].

In this chapter we will further explore the applications of homogenization in response to the COVID-19 pandemic and the multiple diagnostic methodologies this technology has been implemented in and its impact on laboratory safety and overall testing efficiency.
