# A Solid-State Nanopore Biosensor for Rapid Detection of Mycobacterium tuberculosis Antigens in Pediatric Blood Samples

> **NIH NIH K22** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2020 · $106,001

## Abstract

Abstract
Tuberculosis (TB) is a global health threat, but can be difficult to diagnose and manage in pediatric patients due
to the weak performance and non-quantitative nature of frontline diagnostic assays, which function even worse
when used with patients co-infected with human immunodeficiency virus (HIV). There is an unmet need for a
rapid, non-sputum-based quantitative test to detect active TB cases and anti-TB treatment responses in clinically
diverse pediatric populations. The proposed research will overcome these obstacles by developing a solid-state
nanopore biosensor assay that can rapidly diagnose pediatric TB by measuring Mycobacterium tuberculosis
(Mtb)-secreted antigens in patient serum samples. My solid-state nanopore system is easy to operate, has low
fabrication/instrument costs, and can perform high-throughput and ultra-sensitive measurements on specific
Mtb-derived peptides. The robust portability of this platform also allows its use in resource-limited areas that are
subject to high TB prevalence. We identified two highly Mtb-specific peptide fragments of the Mtb virulence
antigens CFP-10 and ESAT-6, and validated their clinical performance as biomarkers for active TB
disease diagnosis using a mass spectrometry-based assay with 201 adult and 123 pediatric patients and
controls chosen from highly relevant cohorts (e.g. HIV-positive/negative, pulmonary/extrapulmonary, Mtb
culture-positive/negative, latent TB, and nontuberculous mycobacteria infections). Similar robust overall
diagnostic sensitivities and specificities obtained using these biomarkers in adults (88.6% / 93.8%) and
children (88.2% / 97.2%) significantly outperformed those reported for other frontline tests. Quantification of
serum Mtb antigen concentration was also informative in monitoring the response to anti-TB treatment in HIV-
positive adults. My recent results show that nanopores can accurately detect CFP-10 and/or ESAT-6
peptides in a pilot cohort of pediatric TB cases, and indicate that statistical analysis of nanopore results for
peptide profiling holds significant diagnostic promise.
Based on these findings, I propose that the portable solid-state nanopore biosensor to be analyzed in these
studies can improve TB diagnosis in children, particularly in resource-limited areas with high TB prevalence. I
will leverage this system and the robustness of Mtb antigen-derived peptide biomarkers to: (1) develop a
nanopore-based TB diagnostic assay; (2) validate this assay in a pediatric cohort with and without HIV co-
infection; and (3) determine whether Mtb antigens concentrations in serum decrease in response to treatment in
a pilot pediatric cohort during anti-TB treatment. Given the success of these proof-of-concept studies, the long-
term goal of the proposed research program is to build prototype devices for large-scale on-site clinical validation
studies in high TB burden regions, and to extend this biosensing platform to the detection of other disease
biomar...

## Key facts

- **NIH application ID:** 9834815
- **Project number:** 5K22AI136686-02
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Chang Liu
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $106,001
- **Award type:** 5
- **Project period:** 2018-12-10 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834815

## Citation

> US National Institutes of Health, RePORTER application 9834815, A Solid-State Nanopore Biosensor for Rapid Detection of Mycobacterium tuberculosis Antigens in Pediatric Blood Samples (5K22AI136686-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9834815. Licensed CC0.

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