# Ultrasensitive Detection of Urine LAM for Point-of-Care Diagnosis of All Forms of Tuberculosis

> **NIH ALLCDC R43** · FLUXUS, INC. · 2021 · $230,284

## Abstract

Project Summary
Tuberculosis (TB) remains one of the most challenging diseases with ten million new cases and two million
deaths yearly, and severe problems due to underdiagnosis and inadequate testing. A point-of-care (PoC) test
for all kinds of TB that is sensitive, quick, simple, and not sputum-based is urgently needed. The most promising
avenue to accomplish this is an immunoassay based on the TB biomarker Lipoarabinomannan (LAM).
Fluxus Inc.’s long-term goal is to develop a novel suite of ultrasensitive, target-agnostic, low-complexity
diagnostic instruments based on optofluidic single-molecule technology that combines integrated optics and
microfluidics on a single chip-based system. The objective of this project is to develop the first PoC compatible
system for detection of LAM in urine for TB diagnosis in collaboration with FIND (Foundation for Innovative New
Diagnostics), the world’s leading non-profit organization for diagnostics for poverty-related diseases. The test
will use single protein detection to achieve the sensitivity of PCR with the relative simplicity and speed of an
immunoassay. Phase I will introduce the innovative elements at the core of the project and result in the
demonstration of the critical performance parameters for a PoC test.
Our objectives will be accomplished by completing the following specific aims that introduce new innovative
concepts: (1) Demonstration of an ultrasensitive LAM assay; (2) Introduction of grating coupled waveguides on
the standard optofluidic architecture; and (3) Integration of an optimized sample-preparation process. Under the
first Aim, we will show that LAM can be identified and quantitated with single-molecule analytical sensitivity.
Specifically, we will develop a bead-based solid-phase extraction assay using best-in-class antibodies (provided
by FIND) and bright fluorescent nanoparticle reporters. An analytical limit of detection of 1 pg/mL and a dynamic
range of 5 logs will be demonstrated – 500x more sensitive than the only available LAM assay (Alere LF-LAM).
The second Aim introduces a new approach using a grating couple to deliver light into the optofluidic chip. This
method is optimized for mass fabrication and PoC instrument complexity and cost. We will adapt the current chip
fabrication process to incorporate the grating coupler and demonstrate 20% light coupling efficiency. Under the
third Aim, we will introduce a disposable pre-prep cartridge for single-step urine LAM extraction/separation
across a fluid-fluid interface with at least 90% capture efficiency.
The proposed work is significant because it will lead to the first ultrasensitive LAM assay for TB diagnosis from
urine at the PoC. The test will have the specificity and sensitivity of PCR detection, but at the low complexity and
cost of an immunoassay, and for diagnosis of all kinds of TB. This concept will then serve as the blueprint for a
broader class of single-molecule diagnostic instruments for rapid pathogen and bi...

## Key facts

- **NIH application ID:** 10255472
- **Project number:** 1R43GH002367-01A1
- **Recipient organization:** FLUXUS, INC.
- **Principal Investigator:** Peter Wagner
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2021
- **Award amount:** $230,284
- **Award type:** 1
- **Project period:** 2021-09-30 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10255472

## Citation

> US National Institutes of Health, RePORTER application 10255472, Ultrasensitive Detection of Urine LAM for Point-of-Care Diagnosis of All Forms of Tuberculosis (1R43GH002367-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10255472. Licensed CC0.

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