| This thesis describes the use of lithographic tools that generate features on the sub-micrometer to sub-millimeter scale, to study biology. Part I examines the interactions between self-assembled monolayers (SAMs) and mammalian cells (chapters 1 to 4). Part II describes biological assays in networks of microfluidic channels (chapters 5 to 7).;Chapter 1 presents a technique that initially confines cells to micropatterns using SAMs, and then releases cells from the confinements to allow free migration. This technique employs electrochemical desorption of oligo(ethyleneglycol)-terminated SAMs. This method is important both for basic studies of cell biology, and for drug discovery where the screening of cell motility under the influence of various compounds may be required. Chapter 2 describes a new class of inert surfaces based on SAMs on palladium and their applications in biology. Chapter 3 applies the technique described in chapter 1 to answer a fundamental question in cell biology: how is the morphological polarity (i.e., the asymmetric shape) of a mammalian cell linked with the direction of its motility? This chapter shows that the direction of movement of cells that are initially confined to asymmetric micropatterns is biased. Chapter 4 discusses the biological applications of SAMs and points to the potential applications of SAMs in tissue engineering.;Chapter 5 describes a quantitative immunoassay for HIV antibodies in a microdilutor network (μDN). This assay carries out serial dilutions in the μDN for quantification of antibodies in one step, using a small volume of solution (∼1 μL), and can analyze multiple antibodies and antigens in one experiment. Chapter 6 shows that the μFN can achieve a large dynamic range of dilution; this range was used to find the optimal concentrations of antibodies to use in immunoassays. Chapter 7 and appendix 3 describe the use of the μDN to generate gradients of biomolecules on surfaces. These methods for fabricating gradients provide important tools for understanding the process of how immobilized gradients of proteins define the polarity (the differentiation of axons from dendrites) of mammalian neurons. |
