# A novel cartridge-based sequencing solution for decentralized M. tuberculosis resistance detection

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $730,369

## Abstract

A novel cartridge-based sequencing solution for decentralized M. tuberculosis resistance detection
Rifampin-resistant tuberculosis (RR-TB) is one of the principal causes of death associated with antimicrobial
resistance. Newer all oral bedaquiline-containing RR-TB regimens, now recommended worldwide, will shorten
treatment and improve outcomes. However, the lack of timely drug susceptibility data due to the slow growth
rate of M. tuberculosis and the need for high containment biological laboratories are major barriers to scale-up
of bedaquiline and other new and repurposed drugs. Xpert MTB/RIF Ultra and other commercial molecular TB
tests can identify rifampin resistance, but cannot inform complete treatment regimens because they are limited
to analyzing only a small number of genetic loci (i.e., “hot spots”). Targeted next-generation sequencing (NGS)
is able to sequence entire genes rapidly without need for culture, and therefore could transform RR-TB clinical
management. Achieving near-patient clinical application, however, has two major bottlenecks: (1) a complex,
unstandardized workflow for preparing clinical samples for NGS, and (2) the cost and infrastructure
requirements of industry-standard Illumina platforms. Partnering with global TB diagnostics leader Cepheid, we
address these barriers by utilizing the ultrasonication, microfluidics, and thermocycler capabilities of the
existing Xpert Ultra cartridge, already in use in over 180 countries, to unite a vetted direct-sample-to-answer
system with a nanopore gene sequencing platform for the first time. Xpert CartSeq, a pioneering cartridge-
based sequencing solution suitable for lower levels of healthcare, achieves robust DNA extraction and
sophisticated library preparation while minimizing user variability and mitigating technical skill requirements.
Through its development as detailed in this proposal, we aim to catalyze the clinical application of NGS in high
burden settings.

## Key facts

- **NIH application ID:** 10719138
- **Project number:** 1R01AI177637-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Soumitesh Chakravorty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $730,369
- **Award type:** 1
- **Project period:** 2023-07-07 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10719138

## Citation

> US National Institutes of Health, RePORTER application 10719138, A novel cartridge-based sequencing solution for decentralized M. tuberculosis resistance detection (1R01AI177637-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10719138. Licensed CC0.

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