SBIR Phase I: Low cost portable system for the rapid detection and drug resistance profiling of Tuberculosis

Impedx Diagnostics, Overland Park KS

Investigators

Abstract

This Phase I SBIR project is directed at developing a portable, sensitive, and affordable device to detect M. tuberculosis (Mtb) in sputum samples and simultaneously determine the multidrug resistance profile of the pathogen, all within 3 days of sputum collection (It takes more than 6 weeks using current technology). By significantly reducing the time to detect viable Mtb and obtain its drug resistance profile in patient specimens, the device being developed promises to improve outcomes and reduce healthcare costs. Tuberculosis (TB) is one of the major public-health challenges in the world today, with an estimated 1.5 million deaths in 2013. More alarmingly, the incidence of multi-drug resistant (MDR) TB is rapidly increasing, especially in low resource environments. Being able to detect the presence of low loads of mycobacteria and gaining knowledge about the drug resistance profile of a particular isolate in 3 days will be a game changer in global community?s efforts to combat the spread of TB (esp. MDR TB). It will lead to better outcomes for patients (less mortality, quicker recovery), and also better public health (less transmission to others and less fostering of drug resistance in populations). The device being developed incorporates two key technologies that enable it to achieve rapid detection and drug-resistance profiling: (1) super-paramagnetic nanoparticles (MNPs) functionalized with moieties that bind to bacterial cells, and (2) microchannel Electrical Impedance Spectroscopy (m-EIS) that is able to detect in real time the growth or death of cells in suspension. The proposed approach involves (a) using MNPs to collect the ~1000 Mtb cells present in 2-10ml of sputum sample into a small (200ul) of growth medium during the standard decontamination process (b) dispensing the 200ul suspension into 16 microwells, each containing different formulations of freeze-dried growth-media and/or drugs of interest (c) monitoring the cells in each well m-EIS. The pre-concentration will take <1 hour, and the monitoring of death/growth/stasis will take 3 days. In Phase I, the team will (1) verify the efficacy of the pre-concentration technique, (2) establish the ability of the m-EIS method to record in real time the death, proliferation, or statis of mycobacteria, and (3) design a prototype cassette containing 16 wells, and fabricating it using 3D-printing (stereolithography). In addition, a detailed design (electrical, mechanical and fluidic) of the automated system (disposables and nondisposable hardware) to be built in Phase II will be completed, and other applications of the core approach explored.