Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in basrelief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (> or = 50 microns), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.

This paper describes the use of surface plasmon resonance (SPR) spectroscopy and self-assembled monolayers (SAMs) to determine the characteristics of functional groups that give surfaces the ability to resist the nonspecific adsorption of proteins from solution. Mixed SAMs presenting different functional groups were prepared for screening using a synthetic protocol based on the reaction of organic amines with a SAM terminated by interchain carboxylic anhydride groups. Surfaces that presented derivatives of oligo(sarcosine), N-acetylpiperazine, and permethylated sorbitol groups were particularly effective in resisting the adsorption of proteins. Incorporation of these groups into single-component SAMs resulted in surfaces that are comparable to (but slightly less good than) single-component SAMs that present oligo(ethylene glycol) in their ability to resist the adsorption of proteins. In the group of surfaces examined, those that resisted the adsorption of proteins had the following properties: they were hydrophilic; they contained groups that were hydrogen-bond acceptors but not hydrogen-bond donors; and they were overall electrically neutral.

This paper examines the hypothesis that surfaces resistant to protein adsorption should also be resistant to the adhesion of bacteria (Staphylococcus aureus, Staphylococcus epidermidis) and the attachment and spreading of mammalian cells (bovine capillary endothelial (BCE) cells). The surfaces tested were those of self-assembled monolayers (SAMs) terminated with derivatives of tri(sarcosine) (Sarc), N-acetylpiperazine, permethylated sorbitol, hexamethylphosphoramide, phosphoryl choline, and an intramolecular zwitterion (-CH2N + (CH3)2CH2CH2CH2SO3 -) (ZW); all are known to resist the adsorption of proteins. There seems to be little or no correlation between the adsorption of protein (fibrinogen and lysozyme) and the adhesion of cells. Surfaces terminated with derivatives of Sarc and N-acetylpiperazine resisted the adhesion of S. aureus and S. epidermidis as well as did surfaces terminated with tri(ethylene glycol). A surface that presented Sarc groups was the only one that resisted the adhesion of BCE cells as well as did a surface terminated with tri(ethylene glycol). The attachment of BCE cells to surfaces could be patterned using SAMs terminated with derivatives of Sarc, N-acetylpiperazine, phosphoramide, and the ZW as the attachment-resistant component and methyl-terminated SAMs as the adhesive component.