Detection and quantification of bacterial biofilms combining high-frequency acoustic microscopy and targeted lipid microparticles

Journal of Nanobiotechnology

Research

Kristina D A Mojica¹  John S Allen²  Michelle L Matter³  Pavlos Anastasiadis⁴ 

[1]Department of Oceanography, School of Ocean and Earth Sciences and Technology, University of Hawaii at Manoa, HonoluluUSA, HI

[2]Department of Biological Oceanography, Royal Netherlands Institute for Sea Research (NIOZ), P.O. Box 59, 1790 AB Den Burg, Texel, The Netherlands

[3]Mechanical Engineering, University of Hawaii at Manoa, 96822, Honolulu, HI, USA

[4]University of Hawaii Cancer Center, 96813, Honolulu, HI, USA

[5]University of Hawaii Cancer Center, 96813, Honolulu, HI, USA

[6]Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, 96822, Honolulu, HI, USA

[7]Mechanical Engineering, University of Hawaii at Manoa, 96822, Honolulu, HI, USA

关键词: Targeted therapy;    Lipid particles;    Biofilm matrix;    Targeted ultrasound contrast agents;    Cancer;    Acoustic microscopy;    Molecular imaging;    Microbubbles;   

DOI  :  10.1186/1477-3155-12-24

 received in 2014-03-06, accepted in 2014-06-24,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundImmuno-compromised patients such as those undergoing cancer chemotherapy are susceptible to bacterial infections leading to biofilm matrix formation. This surrounding biofilm matrix acts as a diffusion barrier that binds up antibiotics and antibodies, promoting resistance to treatment. Developing non-invasive imaging methods that detect biofilm matrix in the clinic are needed. The use of ultrasound in conjunction with targeted ultrasound contrast agents (UCAs) may provide detection of early stage biofilm matrix formation and facilitate optimal treatment.ResultsLigand-targeted UCAs were investigated as a novel method for pre-clinical non-invasive molecular imaging of early and late stage biofilms. These agents were used to target, image and detect Staphylococcus aureus biofilm matrix in vitro. Binding efficacy was assessed on biofilm matrices with respect to their increasing biomass ranging from 3.126 × 103 ± 427 UCAs per mm2 of biofilm surface area within 12 h to 21.985 × 103 ± 855 per mm2 of biofilm matrix surface area at 96 h. High-frequency acoustic microscopy was used to ultrasonically detect targeted UCAs bound to a biofilm matrix and to assess biofilm matrix mechanoelastic physical properties. Acoustic impedance data demonstrated that biofilm matrices exhibit impedance values (1.9 MRayl) close to human tissue (1.35 - 1.85 MRayl for soft tissues). Moreover, the acoustic signature of mature biofilm matrices were evaluated in terms of integrated backscatter (0.0278 - 0.0848 mm-1 × sr-1) and acoustic attenuation (3.9 Np/mm for bound UCAs; 6.58 Np/mm for biofilm alone).ConclusionsEarly diagnosis of biofilm matrix formation is a challenge in treating cancer patients with infection-associated biofilms. We report for the first time a combined optical and acoustic evaluation of infectious biofilm matrices. We demonstrate that acoustic impedance of biofilms is similar to the impedance of human tissues, making in vivo imaging and detection of biofilm matrices difficult. The combination of ultrasound and targeted UCAs can be used to enhance biofilm imaging and early detection. Our findings suggest that the combination of targeted UCAs and ultrasound is a novel molecular imaging technique for the detection of biofilms. We show that high-frequency acoustic microscopy provides sufficient spatial resolution for quantification of biofilm mechanoelastic properties.

【 授权许可】

Unknown   
© Anastasiadis et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.