# A 100-fold more sensitive TB diagnostic based on magnetic concentration and "coffee ring" formation

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2021 · $315,226

## Abstract

The global burden of tuberculosis (TB) stands at ~9 million cases per year; and South Africa is the most
heavily TB-burdened country globally. TB is also the most common opportunistic infection in HIV-infected
persons and it is responsible for 21% of deaths in South Africa. A program of active TB case finding and drug
resistance typing in both urban and rural communities is needed to disrupt TB transmission, yet we currently
lack accessible point of care diagnostics to achieve this goal.
 Particularly in rural South Africa, where TB infection is widespread, microscopic examination of a sputum
smear is the most accessible method for detection of TB. Two major challenges are 1) the more accessible
microscopy methods have a current limit of detection of 10,000 bacilli per ml of sputum which prevents early
detection and allows continued spread of infection, and 2) no methods using bright field microscopy are available
for detecting drug resistant Mycobacterium tuberculosis genotypes.
 In this proposal Vanderbilt University and The University of Cape Town form a partnership to develop
and test bright field microscopy methods for diagnosing TB from sputum. We propose to develop simple methods
to improve the limit of detection of existing and more accessible bright field microscopy of sputum samples to
100 bacilli/ml. Our approach is based on a magnetic concentration strategy and high density deposition onto a
standard microscope slide using the coffee ring phenomenon (Aim 1). Secondly, we propose to develop a
dendrimer-genotyping probe followed by a silica condensation reaction to enable bright field identification of drug
resistant phenotypes (Aim 2). These laboratory designs are then packaged into a simple kit format for initial
clinical testing of retrospective sputum samples in a laboratory as well as in rural South Africa (Aim 3).
 When completed, these simple modifications to the current widely accessible microscopy methods will
identify individuals with low numbers of M. tuberculosis bacilli present in their sputum and enable much earlier
treatment. In addition, enabling the identification of drug resistant bacilli by bright field microscopy will provide
an earlier means to begin more aggressive therapies and further prevent the spread of drug-resistant TB.

## Key facts

- **NIH application ID:** 10231132
- **Project number:** 5R01AI135937-05
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Jonathan Michael Blackburn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $315,226
- **Award type:** 5
- **Project period:** 2017-09-25 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231132

## Citation

> US National Institutes of Health, RePORTER application 10231132, A 100-fold more sensitive TB diagnostic based on magnetic concentration and "coffee ring" formation (5R01AI135937-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10231132. Licensed CC0.

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