Ultrasound Responsive Macrophase-Segregated Microcomposite Films for in Vivo Biosensing

Abstract

Ultrasound imaging is a safe, low-cost, and in situ method for detecting in vivo medical devices. A poly(methyl-2cyanoacrylate) film containing 2 μm boron-doped, calcined, porous silica microshells was developed as an ultrasound imaging marker for multiple medical devices. A macrophase separation drove the gas-filled porous silica microshells to the top surface of the polymer film by controlled curing of the cyanoacrylate glue and the amount of microshell loading. A thin film of polymer blocked the wall pores of the microshells to seal air in their hollow core, which served as an ultrasound contrast agent. The ultrasound activity disappeared when curing conditions were modified to prevent the macrophase segregation. Phase segregated films were attached to multiple surgical tools and needles and gave strong color Doppler signals in vitro and in vivo with the use of a clinical ultrasound imaging instrument. Postprocessing of the simultaneous color Doppler and B-mode images can be used for autonomous identification of implanted surgical items by correlating the two images. The thin films were also hydrophobic, thereby extending the lifetime of ultrasound signals to hours of imaging in tissues by preventing liquid penetration. This technology can be used as a coating to guide the placement of implantable medical devices or used to image and help remove retained surgical items.

Silica Shells/Adhesive Composite Film for Color Doppler Ultrasound Guided Needle Placement

“…The 2 μm boron -doped silica microshells were synthesized by the method reported previously. 27 Briefly, 2 μm polystyrene beads were used as the templates and the sol gel reaction 29 was employed to form silica shells on the templates before removing the polymer cores by calcining the core−shell particles at 550 °C. The microshells exhibit a uniform nanoporous silica wall with a thickness of about 40 nm.…”

“…Two micrometer boron-doped silica microshells were synthesized following the previous report. 27 Loctite 430 super bonder instant adhesive (methyl 2-cyanoacrylate), which is designed for bonding to metal surfaces, was purchased from Henkel Corporation (Rocky Hill, CT). Perfluorooctyltriethoxysilane was purchased from Sigma-Aldrich.…”

“…This phenomenon can be observed with color Doppler imaging . The long duration of US signals in tissues of PFB filled silica shells allows the shells to be used as a tumor marker. , In another study, it was reported that medical devices coated in a 2 μm silica microshells/PMCA composite film can be located within the body cavity due to their ultrasound properties . A macrophase separation during curing of the polymeric adhesive drives the microshells to the surface of the film and air is trapped in the hollow space by the hydrophobic polymer coating.…”

“…25,26 In another study, it was reported that medical devices coated in a 2 μm silica microshells/PMCA composite film can be located within the body cavity due to their ultrasound properties. 27 A macrophase separation during curing of the polymeric adhesive drives the microshells to the surface of the film and air is trapped in the hollow space by the hydrophobic polymer coating. The entrained air (instead of PFC) serves as the contrast agent under color Doppler US imaging.…”

Indocyanine green modified silica shells for colon tumor marking

“…After the growth of a silica layer has been achieved, the particles were calcined to vaporize the polystyrene template, leaving a porous silica shell with a hollow core. [52,[54][55][56][57][58][59][60][61] Because of the synthesis of the shell is done on top of well characterized templates, the shells have a very narrow size distribution and thus are very well suited for medical applications. [60,61] Additionally, calcination of the particles for template removal ensures an inert and uniform surface free of residual reactants, resulting in lower toxicity than other synthesis methods.…”