Ultra-sensitive and rapid detection of nucleic acids and microorganisms in body fluids using single-molecule tethering

Wen-Chih Cheng, Troy Horn, Maya Zayats, Georges Rizk, Samuel Major, Hongying Zhu, Joseph Russell, Zhiguang Xu, Richard E. Rothman and Alfredo Celedon ()
Additional contact information
Wen-Chih Cheng: Scanogen Inc.
Troy Horn: Scanogen Inc.
Maya Zayats: Scanogen Inc.
Georges Rizk: Scanogen Inc.
Samuel Major: Scanogen Inc.
Hongying Zhu: Scanogen Inc.
Joseph Russell: Scanogen Inc.
Zhiguang Xu: Scanogen Inc.
Richard E. Rothman: Johns Hopkins University
Alfredo Celedon: Scanogen Inc.

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Detection of microbial nucleic acids in body fluids has become the preferred method for rapid diagnosis of many infectious diseases. However, culture-based diagnostics that are time-consuming remain the gold standard approach in certain cases, such as sepsis. New culture-free methods are urgently needed. Here, we describe Single MOLecule Tethering or SMOLT, an amplification-free and purification-free molecular assay that can detect microorganisms in body fluids with high sensitivity without the need of culturing. The signal of SMOLT is generated by the displacement of micron-size beads tethered by DNA probes that are between 1 and 7 microns long. The molecular extension of thousands of DNA probes is determined with sub-micron precision using a robust and rapid optical approach. We demonstrate that SMOLT can detect nucleic acids directly in blood, urine and sputum at sub-femtomolar concentrations, and microorganisms in blood at 1 CFU mL−1 (colony forming unit per milliliter) threefold faster, with higher multiplexing capacity and with a more straight-forward protocol than amplified methodologies. SMOLT’s clinical utility is further demonstrated by developing a multiplex assay for simultaneous detection of sepsis-causing Candida species directly in whole blood.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18574-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18574-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18574-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().