Microfluidics-based microbubbles in methylene blue solution for photoacoustic and ultrasound imaging

Contrast agents which can be used for more than one bio-imaging technique has gained a lot of attention from researchers in recent years. In this work, a microfluidic device employing a flow-focusing junction, is used for the continuous generation of monodisperse nitrogen microbubbles in methylene blue, an optically absorbing organic dye, for dual-modal photoacoustic and ultrasound imaging. Using an external phase of polyoxyethylene glycol 40 stearate (PEG 40), a non-ionic surfactant, and 50% glycerol solution at a flow rate of 1 ml/hr and gas pressure at 1.75 bar, monodisperse nitrogen microbubbles of diameter 7 microns were obtained. The external phase also contained methylene blue hydrate at a concentration of 1 gm/litre. The monodisperse microbubbles produced a strong ultrasound signal as expected. It was observed that the signal-to-noise (SNR) ratio of the photoacoustic signal for the methylene blue solution in the presence of the monodisperse microbubbles was 68.6% lower than that of methylene blue solution in the absence of microbubbles. This work is of significance because using microfluidics, we can precisely control the bubbles’ production rate and bubble size which increases ultrasound imaging efficiency. A uniform size distribution of the bubbles will have narrower resonance frequency bandwidth which will respond well to specific ultrasound frequencies.