On-chip generation of microbubbles in photoacoustic contrast agents for dual modal ultrasound/photoacoustic in vivo animal imaging

Dhiman Das,Manojit Pramanik,Kathyayini Sivasubramanian,Chun Yang

doi:10.1038/s41598-018-24713-4

Dhiman Das, Manojit Pramanik + Show 2 more

Open Access

https://doi.org/10.1038/s41598-018-24713-4

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Journal: Scientific Reports	Publication Date: Apr 23, 2018
Citations: 35	License type: open-access

Affiliation: Nanyang Technological University

Abstract

Dual-modal photoacoustic (PA) and ultrasound (US) contrast agents are becoming increasingly popular in recent years. Here, a flow-focusing junction based microfluidic device is used for the generation of nitrogen microbubbles (<7 μm) in two photoacoustic contrast agents: methylene blue (MB) and black ink (BI). The microbubble diameter and production rate could be precisely controlled in both MB and BI solutions. Microbubbles were collected from the outlet of the microfluidic device and optical microscope was used to study the size distributions in both solutions. Next, the microbubbles in both solutions were injected into tubes for phantom imaging experiments. Signal to noise ratio (SNR) of both US, PA imaging experiments were calculated to be 51 dB, 58 dB in MB + microbubbles and 56 dB, 61 dB in BI + microbubbles, respectively. Finally, the microbubbles were injected into the urinary bladder of rats for in vivo animal imaging. The SNR in US imaging with MB + microbubbles and BI + microbubbles were 41 dB and 48 dB, respectively. Similarly, the SNR in PA imaging with the same solutions were 32 dB and 36 dB, respectively. The effect of size and concentration of microbubbles in both MB and BI solutions, on the US and PA signals, has been examined.

Highlights

Photoacoustic (PA) imaging has garnered a lot of attention from the biomedical researchers in recent years due to its high spatial resolution, greater depth of imaging, and wide imaging range from organs to organelles[1,2,3,4]
We report the generation of nitrogen microbubbles using a flow-focusing junction-based microfluidic device in photoacoustic contrast agents, namely, methylene blue and black ink
A higher percentage of glycerol and propylene glycol is desirable as it retains monodispersity of the microbubbles[34] but with black ink (BI), debris and pigments were observed at higher percentages at the flow-focusing junction of the microfluidic device under the microscope

Summary

Introduction

Photoacoustic (PA) imaging has garnered a lot of attention from the biomedical researchers in recent years due to its high spatial resolution, greater depth of imaging, and wide imaging range from organs to organelles[1,2,3,4]. Microbubbles with a stabilized shell comprising of surfactants[32] or phospholipids[33,34] are used as US contrast agents[35] for diagnostic applications, such as imaging the liver and heart[36] These microbubbles may have different gas cores like nitrogen, perfluorobutane, etc.[37]. For US/PA based dual modal imaging, microbubbles have been integrated with several exogenous contrast agents. We envisage the use of microfluidic devices for the continuous generation of nanoparticle coated monodisperse-microbubbles[48,49] as dual modal US/PA contrast agents. Nanoparticles or dye-based contrast agents can fully diffuse in the tissue, microbubbles are more suitable to endovascular imaging owing to its echogenicity and has its own advantages. This can provide structural information of the wall which is important because cancer begins on the wall and spreads from there

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