Long journey to “biopatterning”: surface assays and analysis using closed- and open-space microfluidics

Abstract

The immobilization of biological receptors on surfaces is a first step in many bioassays, a prerequisite for the design of bioelectronic devices, and valuable in certain combinatorial screening strategies. In biosensors, molecules are often immobilized on a solid surface, where they serve as specific ligands for biomolecules such as enzymes, antigens, antibodies, and DNA. Therefore, “biopatterning” receptors on surfaces with great accuracy might be helpful for realizing demanding bioanalytical applications as well as for investigating the role of proteins, or, more generally, the role of complex protein architectures, in biological events that occur on surfaces. In addition, bioanalytical methods that can detect biomarkers at precise locations of challenging samples such as tumor-derived tissue sections are in great need. In this lecture, I will present our efforts on patterning surfaces with proteins and miniaturizing assays with surface-bound receptors. This will cover our early work on microfluidic networks, the development of a library of capillary-driven microfluidic functional elements, and the development of a scanning, non-contact microfluidic technology called the microfluidic probe. I will detail some of the principles underlying these concepts and will illustrate their potential for various applications. I will finally show how a new form of flow over a surface, self-coalescing flows, can be used to dissolve reagents on a surface to effect reactions with great flexibility and accuracy.