# Rapid Culture-Independent Detection of Sepsis Causing Microorganism Directly from Blood

> **NIH NIH R35** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2024 · $403,748

## Abstract

ABSTRACT
Sepsis is a rapid-developing and life-threatening condition and is one of the most common causes of death in
hospitalized patients in the US. Sepsis is generally caused by bacterial, fungal, or viral infection. For well over
half a century, blood culture has been the main diagnostic method, but can only inform us of the presence of
microorganism growth. Although empirical antibiotic treatments are usually started as soon as patients
presenting with signs of severe sepsis, gaps remain in our ability to rapidly identify sepsis-causing pathogens to
guide treatment with higher precision. Studies have shown significant risks to septic patients associated with
delayed results and inappropriate therapy, with each hour of delay in administration of appropriate antibiotics
associated with increased mortality. Although molecular diagnostic technologies are available to improve
identification accuracy, they still rely on a positive blood culture result which may take 12 to 48 h or even longer
if the initial culture is unsuccessful. In this MIRA R35 project, we propose to develop novel nanopore- and click-
chemistry-based approaches for accurate detection of sepsis-causing pathogen independent of blood culture in
about 2 hours to support the early administration of source-directed antibiotics. To fit in the clinical sepsis
treatment procedure, we will employ rapid automatic sample preparation and assay methods. Our methodology
will target proteomic biomarkers, such as outer membrane proteins and virulence factors released into circulation,
as they are less prone to interference of blood components compared to bacterial genomic materials, and are
only secreted by viable microorganisms.
The PI will accomplish the proposed goal by engineering nanopore biosensors meet clinical needs of sepsis
causing pathogen detection and developing multiplex click chemistry amplified nanopore sensing for sepsis
causing microorganism detection and prognosis. The scientific and clinical promises of our research lie in the
innovative biosensing mechanism with unprecedented sensitivity for detecting sepsis causing pathogen protein
biomarkers directly in blood; the user-friendly device prototype readily applicable in clinical settings; and the
discovery of potential prognosis value of virulence factors. In the past years, the PI has established a successful
research trajectory by mentoring a postdoctoral fellow and six PhD students, publishing high-impact research
papers, and securing competitive research grants. We will utilize our group’s diverse expertise on biochemistry,
proteomics, nanotechnology, and microelectronics in conjunction with our collaborators’ expertise on high
specificity high affinity binding ligands and sepsis clinical diagnosis and treatment to ensure the success of
proposed research. The nanopore biosensing platform resulting from this project will also benefit the general in
vitro diagnostics field by offering a sensitive, user-friendly, cost-effect...

## Key facts

- **NIH application ID:** 11206242
- **Project number:** 7R35GM155460-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Chang Liu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,748
- **Award type:** 7
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11206242

## Citation

> US National Institutes of Health, RePORTER application 11206242, Rapid Culture-Independent Detection of Sepsis Causing Microorganism Directly from Blood (7R35GM155460-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11206242. Licensed CC0.

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