ABSTRACT
Functionalized monodisperse microbubbles have the potential to boost the sensitivity and efficacy of molecular ultrasound imaging and targeted drug delivery using bubbles and ultrasound. Monodisperse bubbles can be produced in a microfluidic flow focusing device. However, their functionalization and sequential use require removal of the excess lipids from the bubble suspension to minimize the use of expensive ligands and to avoid competitive binding and blocking of the receptor molecules. To date, excess lipid removal is performed by centrifugation, which is labor intensive and challenging to automate. More importantly, as we show, the increased hydrostatic pressure during centrifugation can reduce bubble monodispersity. Here, we introduce a novel automated microfluidic 'washing' method. First, bubbles are injected in a microfluidic chamber 1 mm in height where they are left to float against the top wall. Second, lipid-free medium is pumped through the chamber to remove excess lipids while the bubbles remain located at the top wall. Third, the washed bubbles are resuspended and removed from the device into a collection vial. We demonstrate that the present method can (i) reduce the excess lipid concentration by 4 orders of magnitude, (ii) be fully automated, and (iii) be performed in minutes while the size distribution, functionality, and acoustic response of the bubbles remain unaffected. Thus, the presented method is a gateway to the fully automated production of functionalized monodisperse microbubbles.
ABSTRACT
BACKGROUND: Electroconvulsive therapy is an effective treatment for mood disorders. There is, however, no consensus about the safety of use in patients with metallic skull implants even though these patients are at higher risk of developing mood disorders. AIM: To bundle the existing literature concerning the use of electroconvulsive therapy in patients with metallic skull implants and to examine the evidence concerning safety and efficacy in this group. METHODS: Relevant case reports and literature reviews published since 1950 were located using PubMed. RESULTS: We selected and reviewed 37 case reports. There were no complications related to the interaction between electroconvulsive therapy and the metallic objects. Psychiatric outcomes were positive in 95% of cases. CONCLUSION: There is no evidence that electroconvulsive therapy is unsafe in patients metallic skull implants. With appropriate caution, its use can be considered on a case-by-case basis by psychiatrists.