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

Journal of Nanobiotechnology

Michelle L Matter³  John S Allen¹  Kristina D A Mojica²  Pavlos Anastasiadis¹ 

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

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

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

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

Others  :  1146388
DOI  :  10.1186/1477-3155-12-24

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

【 摘 要 】

Background

Immuno-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.

Results

Ligand-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).

Conclusions

Early 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】

   
2014 Anastasiadis et al.; licensee BioMed Central Ltd.

【 图 表 】

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