Stand-alone platform for time-effective early detection of sepsis

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Author
Brero, Giorgio
Atakan, H. Baris
Odermatt, Pascal D.
Valentin, Tom
Dittrich, Pestra S.
Kurth, Felix
DOI
Abstract
Sepsis causes approximately 250,000 deaths annually in the United States and affects around 1.5 million people. This condition presents an extremely rapid fatal escalation, and its early detection is crucial for patients’ survival. Clinical screening methods implement pathogens detection in human liquid biopsy, along with associated cell biomarkers, to collect essential insights into the patient's physiological and pathological status. Traditional sepsis detection methods include microbiological studies, molecular diagnostics, and cell biomarkers expression quantification. However, these techniques often require multiple sample manipulations, which can increase time of sepsis detection and the risk of sample contamination. Among all these methods, blood culture remains the most widely used, time-consuming, clinical technique for quantitative detection of gram-negative and gram-positive bacteria, in affected patients. In the field of early sepsis detection, researchers are increasingly focusing on rapid and precise techniques for analysis of human body fluids, such as blood and urine, which contain disease-related biomarkers in form of circulating cells, bacteria, and vesicles. In response to these challenges, we developed a stand-alone, automatized, cost-effective, and open-source platform for fast sepsis patient screening. This device features two microfluidic cartridges designed for liquid biopsy manipulation and filtration (cartridge 1), and antibody labelling and real-time detection of sepsis-related bacteria (cartridge 2). The disposable microfluidic cartridges separate pathogens from whole human blood (4 ml) or urine, add the appropriate gram-positive and gram-negative antibodies, remove air bubbles and unbound staining solution. Subsequently, the sample containing labelled bacteria is focused into a 10 µm diameter flow stream, allowing for in-depth optical analysis. The full process is automated and takes a total time of 40 minutes. This compact, low-cost microfluidic platform minimizes the required sample volume, and we target bacteria detection at a concentration of 100 CFU/mL in whole blood. Moreover, the device can be interfaced with modern laser-equipped microscopes, accelerating detection and making it accessible to a wide range of optical instruments. With the compensation of the background signal and the implementation of a dedicated CMOS photonic chip, we plan to use the platform for the real-time detection and quantification of cancer-released extracellular vesicles from liquid biopsy samples.
Publication Reference
Physics and Chemistry of Microfluidics GRC, Lucca, Italy
Year
2025-06-01
Sponsors
Biosystems Engineering and Automated Sample Handling, BU Life Sciences & IND 4.0, Allschwil and Alpnach, Switzerland Bioanalytics Laboratory, Department of Biosystems and Science Engineering, ETH Zürich, Basel, Switzerland State Secretariat for Education, Research and Innovation (SERI) European Union under the Horizon Europe program GA ID: 101093171