3D printing in Clinical Diagnostics: A Versatile Tool to Develop Testing Devices for the Diagnosis of Infectious Diseases

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3D printing (3DP) has recently emerged as an advanced manufacturing technology in the pharmaceutical and biomedical industries. 3DP has virtually become a synonym for rapid prototyping. The ease of use and low cost of in-house 3D printing has also revolutionized product development, and many manufacturers of medical tools have adopted the technology to produce brand-new medical devices and surgical instruments. 3DP allows for a fast feedback loop which accelerates design development; designers and manufacturers can rely on the use of early 3D printed parts to support clinical trials or early commercialization while the final design is still being optimized. This relationship was crucial in support of enhanced health care and general emergency response, as shown during the COVID-19 pandemic. A few examples where 3DP technologies were used to validate product efficacy include 3DP nasal pharyngeal swabs, multiplexing of bi-level positive airway pressure (BiPAP) machines to support multiple patients, patient-specific dental moulding, and antigen testing kits for COVID-19. In this dissertation, I show the versatility of 3D printing within the infectious disease workflow. Firstly, I demonstrate the use of 3D printing in patient sample collection through the development of a novel 3D manufacturing and efficacy validation for nasal pharyngeal (NP) swabs. With the aim to develop a swab (a) 3D printed with complex tip structures for enhanced sample collection efficacy, eliminating the need to apply flocks at the tips (b) scalability with a network of 3D printing capacity in biomedical devices and biocompatible material applications, and (c) ability to rapidly iterate prototypes quickly and effectively without incurring costs of machining moulds for injection moulding. In the following chapter, I discuss the importance and use of rapid manufacturing techniques to develop diagnostic assay kits for various diseases; predominantly in the development of point-of-care (POC) devices through the combination of microfluidic and microelectromechanical systems (MEMS). 3DP techniques can be utilized to develop various fluidic systems to streamline laboratory testing methodologies. I explore the development of a centrifugal microfluidic platform and the manufacturability of various centrifugal fluidic systems within the limitation of 3DP. This work aims to provide the building blocks of the 3D printing of various centrifugal microfluidic modules and establishes a proof-of-concept AST platform for bloodstream infections by sensing and monitoring the growth and antibiotic susceptibility of E. coli. Finally, I show the utility of 3DP in clinical diagnostics through the rapid development of a custom 96-well plate platform; microbial containment device (MCD) and software package FUGU-MS – Filtering Utility for Grouping untargeted mass spectrometry data and open-source software tool to compliment the metabolic data acquired via the MCD. The 3D printed MCD that allows water-soluble metabolites to diffuse from a microbial culture well into a bacteria-free well through a semi-permeable membrane, which allows for streamline sample processing for clinical diagnostics of bloodstream infections. The MCD validated through the analysis of the metabolic flux to identify different strains of bacteria, including Escherichia coli, Klebsiella pneumonia, Enterococcus faecalis and Staphylococcus aureus following a 4-hour incubation period of various bloodstream and urinary tract pathogens and direct sampling onto a Q Exactive HF Hybrid Quadrupole-Orbitrap Mass Spectrometer.
3D printing, infectious disease, 3D printed swabs COVID, centrifugal microfluidics, blood stream infection, Metabolomics
Aburashed, R. (2023). 3D printing in clinical diagnostics: a versatile tool to develop testing devices for the diagnosis of infectious diseases (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.