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Nanomechanical detection to empower robust monitoring of sepsis and microbial adaptive immune system-mediated proinflammatory disease

Thanapirom, Kessarin; Al-Akkad, Walid; Pelut, Aylin; Sadouki, Zahra; Finkel, Jemima B; Nardi-Hiebl, Stefan; Vogt, Wieland; ... Ndieyira, Joseph W; + view all (2024) Nanomechanical detection to empower robust monitoring of sepsis and microbial adaptive immune system-mediated proinflammatory disease. Scientific Reports , 14 , Article 29979. 10.1038/s41598-024-80126-6. Green open access

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Abstract

The correlation between circulating microbes and sepsis as well as proinflammatory diseases is increasingly gaining recognition. However, the detection of microbes’ cell-free DNA (cfDNA), which exist at concentrations of a billion times lower than blood proteins, poses a significant challenge for early disease detection. Here, we present Nano mechanics combined with highly sensitive readout sequences to address the challenges of ultralow counts of disease biomarkers, thus enabling robust quantitative monitoring of chronic medical conditions at different stages of human disease progression. To showcase the effectiveness of our approach, we employ fragments of cfDNA and human cell secretory proteins as models with predictive capabilities for human diseases. Notably, our method reveals a reliable representation over an impressive three to four orders of magnitude in the detection limit and dynamic range, surpassing commercially available quantitative polymerase chain reaction (qPCR) commonly used in routine clinical practice. This concept underpins a highly sensitive and selective medical device designed for the early detection of circulating microbes in patients undergoing intensive cancer therapy. This will help pinpoint individuals at risk of complications, including damage to the intestinal barrier and development of neutropenic fever/Sirsa/Sepsis. Moreover, this approach introduces new avenues for stratifying antibiotic prophylaxis in proinflammatory diseases.

Type: Article
Title: Nanomechanical detection to empower robust monitoring of sepsis and microbial adaptive immune system-mediated proinflammatory disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-024-80126-6
Publisher version: http://dx.doi.org/10.1038/s41598-024-80126-6
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10201037
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