Standalone Lab-on-a-Chip Systems toward the Evaluation of Therapeutic Biomaterials in Individualized Disease Treatment

Abstract

As each tumor is unique, treatments should be individualized in terms of their drug formulation and time dependent dosing. In vitro lab-on-a-chip (LOC) drug testing is a viable avenue to individualize treatments. A drug testing platform in the form of a customizable standalone LOC system is proposed for treatment individualization in vitro. The platform was used to individualize the treatment of pancreatic cancer by using PANC-1 and MIA PaCa-2 cell lines cultured on-chip. Using on-chip drug uptake, growth, and migration inhibition assays, the therapeutic effect of various treatment combinations was analyzed. Thereafter, optimized treatments were devised for each cell line. The individualized dosage for MIA PaCa-2 cell line was found to be between 0.05–0.1 μg/μL of doxorubicin (DOX), where the greatest growth and migration inhibition effects were observed. As the PANC-1 cell line showed resistance to DOX only formulations, a multidrug approach was used for individualized treatment. Compared to the DOX only formulations, the individualized treatment produced the same degree of migration inhibition but with 5–10 times lower concentration of DOX, potentially minimizing the side-effects of the treatment. Furthermore, the individualized treatment had an average of 672.4% higher rate of growth inhibition. Finally, a preliminary study showed how a tested formulation from the LOC system can be translated for use by employing a nanoparticle system for controlled delivery, producing similar therapeutic effects. The use of such systems in clinical practice could potentially revolutionize treatment formulation by maximizing the therapeutic effects of existing treatments while minimizing their potential side effects through individualization of treatment