Hydrodynamic Flow Confinement Using a Microfluidic Probe

Photolithography, the art of patterning surfaces using light projected through an optical mask and chemicals sensitive to light, reached an extraordinary level of sophistication for producing microelectronic components reaching sub-20 nm dimensions on a massive manufacturing scale with extremely high yields. While photolithography had started in the 1960s for fabricating integrated circuits, it essentially remained confined to the structuring and modification of inorganic surfaces and materials. Strong progress on sequencing genomes, an increased understanding of the complexity of cells, tumors, tissues and organs, and emerging work on cell–environment interactions called for new techniques that could tailor biological interfaces and analyze challenging biological specimens. It took, for example, until the 1990s before peptides and oligonucleotides were patterned on glass slides using combinatorial masks and photolithography [1, 2], DNA [3] and protein [4] microarrays were demonstrated, self-assembled monolayers were patterned using soft lithography [5], and various “inks” were deposited on surfaces with nanometer precision using scanning probe methods [6]. All together these techniques are impressive because they can deal with many types of inks, are precise, can cover very large areas, and can be fast and inexpensive. There is, however, a general need for controlling the chemical environment during the deposition of species onto surfaces, the analysis of surfaces, and the study of (bio)interfaces. Controlling the chemical environment here means being able to work with various solutions (biological buffers, culture medium, solvents, etc.) without drying artifacts, potentially at a specific temperature, and being able to change this chemical environment in a flexible manner. The control over the chemical environment on a surface can be achieved, for example, by (i) isolating areas of a surface using microfluidic channels and laminar streams of solutions [7, 8], (ii) applying locally chemicals using a probe [9], or (iii) compartmentalizing chemicals near a surface using nonmiscible liquids [10, 11]. The ability to control a chemical environment on a surface is probably most interesting for biological applications for several reasons: First, investigating the structure and function of proteins, cells, and tissues on surfaces is fundamental. Second, biomolecules and