| In this research, trans-disciplinary advances are made in the fields of microfluidics, point of care testing (POCT) and cancer screening. A tumor-bearing subject is injected with a cancer-targeting gene delivery vector that selectively induces production of a secretable serum biomarker from tumor tissue and not healthy tissue is coupled with biomedical microfluidic devices which sample blood from the subject and perform analysis on the blood for presence of the serum. The unifying goal of these technologies is the detection of cancer by identifying an exogenously induced serum biomarker in subjects in a tumor-dependent manner. First, methods for rapidly fabricating microfluidic devices are developed so that the devices used as part of the cancer screening method can be designed and optimized in an iterative fashion. Second, flow control in microfluidic devices is achieved using a new design for a modular pinch valve for incorporation into microfluidic devices produced in rigid polymer substrates. Then a microfluidic device for intermittent blood sampling from catheterized patients is designed, produced and characterized for fluid control, sample collection and cross-contamination. Next a, a microfluidic blood analysis chip is designed to incorporate three functions: serum separation, hematocrit evaluation and serum biomarker quantitation. The devices function is characterized for serum separation on small blood samples (<1.5 muL), evaluation of hematocrit using a novel gray scale image analysis approach and detection of serum biomarker down to 10 ng/mL. Finally, a novel cancer screening method is developed whereby an oncolytic Herpes Simplex Virus is engineered to deliver a genetic payload which induces secretable biomarker expression in a tumor selective manner. The novel HSV mutant is characterized in vitro and in vivo for several tumor models in different anatomical locations. Specific tumor models are identified as highly susceptible to this screening approach as seen in extremely high biomarker induction while other tumor models with lower biomarker expression are still identifiable by this screening approach. |
