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Patient derived organoids have emerged as robust preclinical models for screening anti-cancer therapeutics. Current 2D culturing methods do not provide physiological responses to therapeutics, therefore 3D models are being developed to better reproduce physiological responses. 3D culturing however often requires large initial cell populations and one week to one month to grow tumors ready for therapeutic testing. As a solution a 3D culturing system has been developed capable of producing physiologically relevant tumors in an expedited fashion while only requiring a small number of initial cancer cells. A bi-layer microfluidic system capable of facilitating active convective nutrient supply to populations of cancer cells facilitates expedited growth of cancer cells when starting with populations as small as 8 cells. The system has been shown to function well with adherent and non-adherent cell types by expediting cell growth by a factor ranging from 1.27 to 4.76 greater than growth under static conditions. Utilizing such an approach has enable to formation of tumors ready for therapeutic screening within 3 days and the ability to perform therapeutic screening within the microfluidic system is demonstrated. A mathematical model has been developed which allows for adjustments to be made to the dynamic delivery of nutrients in order to efficiently use culture media without excessive waste. We believe this work to be the first attempt to grow cancers in an expedited fashion utilizing only a convective nutrient supply within a microfluidic system which also facilitates on-device therapeutic screening. The developed microfluidic system and cancer growth method have the potential to offer improved drug screening for patients in clinical settings. 

Nanoparticle therapeutic delivery is influenced by many factors including physical, chemical, and biophysical properties along with local vascular conditions. In recent years, nanoparticles of various shapes have been fabricated and have shown significant impact on transport efficiency. Identification of which nanoparticle shape helps to improve the therapeutic delivery process allows for enhanced therapeutic effects, yet is hard to be quantified in vivo due to the complex nature of the in vivo environment. In this work, we turn to biological models as a guide for informing improved nanoparticle therapeutic delivery, and quantify the contribution of various factors on delivery efficiency. Here we show that with a mimetic blood vessel, improved therapeutic delivery is achieved using long filamentous rod nanoparticles under low pressure conditions. When considering medium pressure conditions, a combination of nanoparticle shapes presents improved therapeutic delivery over the treatment time-course starting with long filamentous rod nanoparticles, followed by short rod nanoparticles. Conditions of high pressure required a combination of short rod nanoparticles, followed by spherical nanoparticles to achieve enhanced therapeutic delivery. Overall, improvement of therapeutic delivery via nanoparticle carriers is likely to require a combination of nanoparticle shapes administered at different times over the treatment time-course, given patient specific conditions.