Microfluidic production of nanoscale perfluorocarbon droplets as liquid contrast agents for ultrasound imaging

Abstract

Liquid perfluorocarbon (PFC) nanodroplets may have a better chance to extravasate through inter-endothelial gaps (400-800 nm) into tumor interstitium for extravascular imaging, which holds promise as an innovative strategy for imaging-guided drug delivery, early diagnosis of cancer and minimally invasive treatment of cancer. Currently available emulsion technologies still face challenges in reducing droplet sizes from the microscale to the nanoscale. To control size and ensure monodispersity of PFC nanodroplets, we developed a flame-shaped glass capillary and polydimethylsiloxane (PDMS) hybrid device that creates a concentric flow of the dispersed phase enclosed by the focusing continuous phase at the cross-junction. Through adjustment of the pressure applied, a stable tip-streaming mode can be obtained for PFC nanodroplet generation. Using this device, we synthesized various kinds of PFC nanodroplets as small as 200 nm in diameter with polydispersity index (PDI) <0.04. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were carried out for the characterization of the PFC nanodroplets. Finally, ultrasound imaging was conducted to demonstrate that the liquid PFC nanodroplets can be used for enhancing the ultrasound contrast upon vaporization.

Artificial oxygen carriers: a new future?

“…PFCs may also be used as contrast agents [ 13 ] and, in conjunction with magnetic resonance imaging, as infection tracers [ 14 ].…”

Artificial Blood: A Futuristic Dimension of Modern Day Transfusion Sciences

“…Recent literature points towards newer vistas of therapeutic application of blood substitutes in clinical practice ranging from foetal hypoxia in preeclampsia [37], cerebral ishchaemia [38] and liver transplantation [39]. Additionally, they are being utilized as contrast agents [40] or infection tracers [41]. Future research initiatives in this context should, therefore, be directed towards providing adequate quantities of safe, efficacious, commercially viable alternatives with lesser drawbacks which will reduce dependency on donated blood and reduce mortality due to transfusion requirements.…”

“…2) Longer Shelf Life: They can be stored at room temperatures for prolonged periods (1-3 years) and are ready to be used as compared to stored blood which can be stored for around [35][36][37][38][39][40][41][42] days. There is no necessity of refrigeration of these products.…”

<p>Review of the Application of Nanovesicles and the Human Interstitial Fluid in Gastrointestinal Premalignant Lesion Detection, Diagnosis, Prognosis and Therapy</p>

“…In addition, NVs should be engineered to be of an adequate size, ideally around 400–800nm, to transport sufficient therapeutic drugs while also being small enough to move through the TIF and infiltrate the tumor. Nanodroplets that are capable of tumor internalization have been designed for extravascular imaging 92. This method could potentially be applied in a similar manner for the early diagnosis and treatment of GI premalignant lesions.…”