Fabrication and Testing of an Integrated Cartridge for Point of Care Infectious Disease Diagnosis
Authors:Thomas Carey, Kimberly Chen
- Angelika Niemz, Associate Professor, Keck Graduate Institute
- Hsiang-Wei Lu, Research Scientist, Keck Graduate Institute
Infectious disease diagnosis in developing countries often is prohibitively expensive, involves complex instruments requiring trained operators, and is slow, necessitating patients travel to a health-care facility multiple times to be tested and diagnosed. To diagnose active tuberculosis in most low-resource settings, an inexpensive, simple, self-contained device is required. Our goal is to develop a portable, battery-powered nucleic acid testing device, utilizing disposable cartridges, with consumables costing less than $10, and a reusable instrument costing less than $100. Previously, our group has developed an initial version for a nucleic acid amplification and detection cartridge plus associated instrument, and using this system has demonstrated detection of 3000 copies of Mycobacterium tuberculosis (M.tb) genomic DNA in less than 30 minutes. The project presented herein focused on the design and manufacturing of a refined amplification and detection cartridge, plus associated instrument. We optimized the injection-molding process used for in-house fabrication of the cartridge body, fabricated and tested custom miniaturized passive one-way valves, and integrated a previously designed miniaturized electrolytic pump into the system. Related to the instrument, we designed, built, and tested a refined custom printed circuit board that controls heating, pumping, and timing. Compared to prior versions, this electronics module contains an improved current source design to drive the electrolytic pumps, and systems checks to ensure proper connection with the pump electrodes. We demonstrated that the electrolytic pumps on the cartridge driven by the instrument operate appropriately. However, further improvements are required in the valve design and sealing of fluid conduits before M.tb detection can be executed in this cartridge. Ultimately, our goal is to develop a fully integrated cartridge, which combines amplification and detection with sample preparation for user friendly and rapid sample to answer testing.