Human organ-on-a-chip consists of microfluidic devices designed to culture human cells so as to recapitulate physiological tissue or organ-level functions. They are animal-alternatives to better predict drug responses and interactions in human. Microfluidics can mimic systemic circulation between multiple organ/tissues to model drug metabolism and pharmacokinetics (DMPK) . Our goal is to develop novel integrated 3D microfluidic systems that enable us to control, perturb and measure cells with increased precision and translate them into applications in dug discovery.
Patient derived 3D micro-tumor chips for personalized cancer treatments (in collaboration with Ramanuj DasGupta, Genome Institute of Singapore)
The worst-case scenario in cancer therapy is a double whammy of failed treatment and side effects, thus necessitating the need to develop strategies that can predict patient’s treatment responses and customize a personalized treatment regime. Current approaches include using genetic tests and humanized mouse models; however, genetic tests are not readily available for all cancer types and mouse avatars are expansive and impractical for routine drug screening. Our goal is to Patient-Derived Micro-Avatar Chips (PD-MAC) for various cancer indications by integrating patient-derived tumor cells into a miniaturized, screenable microfluidic platform. By demonstrating that the PD-MAC models can reliably predict individual patient tumor cells’ sensitivity to drug or immune-cell mediated cytoxicity as compared to in vivo or clinical responses, the PD-MAC will enable direct screening of patient’s responses to guide treatment decisions without prior knowledge of underlying genetic mutations, thereby creating a scalable and economically viable disruptive technology directly benefitting patient outcome and survival.
Modular organs-on-chips for probing systemic interactions
Microfluidic organs-on-chips are being developed for various in vitro testing applications due to their ability to mimic local physiological tissue environment. More importantly, multiple tissue chips can be connected fluidically to mimic the systemic interactions between multiple tissues, such as during drug induced skin-sensitization and bioactivation of anti-tumor pro-drugs. To date, microfluidic organs-on-chips are designed as integrated systems which are lab / company-specific, making it difficult to standardize and manufacture. To circumvent the limitations of integrated microfluidic systems, our approach is to design modular microfluidic systems in order to facilitate easy and flexible configuration of microfluidic systems through the assembly of various standardized microfluidic modules, which perform specific functional operations applicable in cell-based assays e.g. cell culture, fluid delivery, pumping. Each microfluidic module will include a universal fluidic connector that can form a reversible seal with each other.