Investigations at the cellular and molecular level offer exciting opportunities for gaining fundamental insights into biological processes, which eventually help diagnose and treat diseases. Well-matched in size, micro- and nano-engineered devices are ideally suited for these purposes and offer unique capabilities, from highly localized and deterministic sample manipulation to precise quantitative measurements. In this talk, I will first focus on our efforts to develop microfluidic systems (a.k.a Lab-on-a-Chip) with embedded sensor networks for quantitative analysis of biological samples. Typically, microfluidic devices lack an embedded sensing scheme and hence are often used for upstream sample preparation, while quantitative measurements are delegated to specialized external laboratory instruments. Such reliance on external instruments hampers widespread adoption of biochips in point-of-care settings, where they can be truly transformative in healthcare delivery. To this end, I will present microfluidic devices with built-in electrical sensor networks that digitally monitor the state of each and every cell in a microfluidic device to perform high-throughput physical and chemical measurements. I will then present our work on using paper as a low-cost substrate to create programmable microfluidic systems for molecular detection. I will demonstrate how capillary fluid flow in these systems can be controlled through imprinted timer valves to perform complex molecular analyses that otherwise require advanced instruments and manual labor. I will conclude by presenting clinical applications of some of our work, including our microfluidic devices that can deterministically scan cancer patient blood samples and isolate metastatic circulating tumor cells for targeted therapies.